Original Article
A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis
N Engl J Med 2006; 354:899-910March 2, 2006
- Abstract
Background
Natalizumab is the first α4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.
Methods
Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.
Results
Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan–Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent).
Conclusions
Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis. Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing multiple sclerosis. (ClinicalTrials.gov number, NCT00027300.)
Media in This Article
Figure 1
Patient Enrollment.Figure 2
Kaplan–Meier Plots of the Time to Sustained Progression of Disability among Patients Receiving Natalizumab, as Compared with Placebo.Article Activity
- Article
Relapsing multiple sclerosis is characterized by the intermittent development of inflammatory lesions in the brain and spinal cord, resulting in plaques of demyelination and axonal loss. Lymphocyte migration across the blood–brain barrier is thought to be an important early step in the formation of lesions.1 The interaction of α4β1 integrin, a protein on the surface of lymphocytes, with vascular-cell adhesion molecule 1 (VCAM-1), which is expressed on the surface of vascular endothelial cells in brain and spinal cord blood vessels, mediates the adhesion and migration of lymphocytes in areas of inflammation.2-6 Furthermore, the interaction of α4β1 integrin with ligands such as fibronectin3 and osteopontin7 may modulate the survival, priming, and activation of leukocytes that have gained access to the parenchyma of the central nervous system.8-11 Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals), which belongs to a new class of selective adhesion-molecule inhibitors, binds to the α4 subunit of α4β1 and α4β7 integrins and blocks binding to their endothelial receptors (VCAM-1 and mucosal addressin-cell adhesion molecule 1, respectively), thereby attenuating inflammation.12 Natalizumab may also modulate ongoing inflammatory reactions by inhibiting the binding of α4-positive leukocytes with fibronectin and osteopontin.
Current therapies for multiple sclerosis, including interferon beta and glatiramer acetate, are only moderately effective, reducing the annualized rate of relapse by about one third.13-16 On the basis of the favorable results of a phase 2 trial of natalizumab in patients with relapsing multiple sclerosis,17 a two-year phase 3 clinical trial, the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, was initiated to confirm the efficacy of natalizumab in relapsing multiple sclerosis and to evaluate the safety of long-term treatment.
Methods
Patients
Ninety-nine clinical centers in Europe, North America, Australia, and New Zealand enrolled 942 patients beginning on November 6, 2001. All patients gave written informed consent. The study protocol was developed by the investigator advisory committee and sponsors, was approved by central and local ethics committees, and was overseen by an independent safety-monitoring committee. Study data were collected by the investigators and an independent organization (PPD International) and were held and analyzed by Biogen Idec and Elan Pharmaceuticals. All members of the publication committee had full access to the data. During the study, the investigator advisory committee and sponsor representatives met at least monthly to discuss study progress. The manuscript was written by Drs. Polman and Panzara, with input from all coauthors. All authors vouch for the veracity and completeness of the data and data analysis.
Enrollment was limited to men and women who were between the ages of 18 and 50 years and had a diagnosis of relapsing multiple sclerosis18; who had a score of 0 to 5.0 on the Expanded Disability Status Scale (EDSS), a rating that ranges from 0 to 10, with higher scores indicating more severe disease19; who had undergone magnetic resonance imaging (MRI) showing lesions consistent with multiple sclerosis; and who had had at least one medically documented relapse within the 12 months before the study began. Patients with disease that was categorized as primary progressive, secondary progressive, or progressive relapsing were excluded.20 Additional exclusion criteria included the following: a relapse within 50 days before the administration of the first dose of the study drug, treatment with cyclophosphamide or mitoxantrone within the previous year, or treatment with interferon beta, glatiramer acetate, cyclosporine, azathioprine, methotrexate, or intravenous immune globulin within the previous 6 months. Patients who had received treatment with interferon beta, glatiramer acetate, or both for more than six months were also excluded.
Study Design and Randomization
Patients were randomly assigned in a 2:1 ratio to receive either natalizumab (at a dose of 300 mg) or placebo by intravenous infusion every 4 weeks for up to 116 weeks. Patients were randomly assigned to treatment that was stratified according to study site in blocks of three (two active, one placebo) with the use of a computer-generated block randomization schedule and a multidigit identification number, implemented by an interactive voice-response system. All study personnel, patients, sponsor personnel involved in the conduct of the study, and the investigator advisory committee were unaware of treatment assignments throughout the study.
Study Procedures and End Points
At each study site, primary and backup examining neurologists and primary and backup treating neurologists were designated. Treating neurologists were responsible for all aspects of patient care, including the management of adverse events and the treatment of relapsing disease. Examining neurologists performed objective evaluation with use of the EDSS and neurologic examination during all study visits; they were not in contact with patients in any other capacity, so as to reduce the possibility of being unblinded by side effects or laboratory assessments.
Patients visited the clinic every 12 weeks for scoring on the EDSS, blood chemical and hematologic analyses, evaluation of adverse events, and testing for anti-natalizumab antibodies. Patients were also seen by the treating neurologist at unscheduled visits within 72 hours after the onset of new neurologic symptoms. If a relapse was suspected, the patient was referred to the examining neurologist, who evaluated the patient within five days after the event. Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted for at least 24 hours and were accompanied by new neurologic signs found by the examining neurologist. At the discretion of the treating neurologist, relapses were treated with intravenous methylprednisolone at a dose of 1000 mg per day for three or five days. Patients whose disability progression was sustained for 12 weeks were allowed to continue participation in the study and were given the option of adding an available treatment for multiple sclerosis as rescue medication per protocol while continuing to receive the study drug. Patients were strongly encouraged to remain in the study for follow-up assessments even if they had discontinued the study drug.
Proton-density–weighted or T2-weighted and gadolinium-enhanced T1-weighted MRI scans of the brain were obtained at baseline, at week 52, and at week 104. Contiguous, 3-mm-thick axial slices through the whole brain were acquired. MRI analysis was performed at the Central Reading Center at the Institute of Neurology, University College London, by experienced raters who were unaware of treatment assignment.
The study had primary and secondary end points at two prespecified times. An assessment of the inflammatory characteristics of the disease was performed at one year and of the progression of the irreversible destructive process at two years. At one year, the primary end point was the rate of clinical relapse, and secondary efficacy end points were the number of new or enlarging hyperintense lesions as detected by T2-weighted MRI, the number of lesions as detected by gadolinium-enhanced MRI, and the proportion of relapse-free patients. At 2 years, the primary end point was the cumulative probability of sustained progression of disability, which was defined as an increase of 1.0 or more on the EDSS from a baseline score of 1.0 or more or an increase of 1.5 or more from a baseline score of 0 that was sustained for 12 weeks (progression could not be confirmed during a relapse). Secondary efficacy end points at two years were the rate of clinical relapse, the volume of lesions as detected by T2-weighted MRI, the number of new hypointense lesions as detected by unenhanced T1-weighted MRI, and the progression of disability as measured by the Multiple Sclerosis Functional Composite. This report presents data on the one-year and two-year primary end points and the one-year secondary end points for which data were also available at two years.
Binding antibodies against natalizumab were assessed with the use of an enzyme-linked immunosorbent assay. Samples that were positive for binding antibodies (0.5 μg per milliliter) were further tested by flow cytometry to assess the ability of the antibodies to interfere with the binding of natalizumab to α4 integrin.
Statistical Analysis
The estimate of sample size was based on data from previous trials of natalizumab17 and of interferon beta-1a13 with the use of two-sided tests, with an alpha level of 0.05. The annualized rate of relapse at one year was predicted to be 0.6 with natalizumab and 0.9 with placebo. For an annualized relapse rate, a likelihood-ratio test was used to determine the sample size required for 90 percent power (n=765), with a 2:1 ratio of natalizumab to placebo. With an assumed dropout rate of 15 percent and rounding, the number of patients needed was estimated to be 900. In order to power the study for the two-year end point of disability progression, progression rates at the end of two years were assumed to be 34.9 percent for the placebo group and 22.7 percent for the natalizumab group. Simulations of the log-rank test for survival were run with 60 percent of the accrual in the first 24 weeks and the remainder in the next 24 weeks, assuming a 20 percent dropout rate over the 2-year study. The sample size of 900 provided 90 percent power with the use of a Bonferroni adjustment for multiple end points, maintaining the type 1 error rate of 0.05.
P values that are reported for most baseline demographic and disease characteristics were calculated with the use of a t-test to compare differences in means. The exceptions were sex, race, and diagnosis of multiple sclerosis by the McDonald criteria,18 for which a chi-square statistic was used to compare treatment groups.
The primary end point at two years was the cumulative probability of sustained progression of disability. This was assessed by an analysis of the time until the onset of the progression of disability that was sustained over 12 weeks with the use of the Cox proportional-hazards model. The annualized rate of relapse (the primary end point at one year) was calculated by Poisson regression; relapses that occurred after rescue treatment was initiated for patients who had had a sustained progression of disability (per protocol) were censored. The predefined statistical models included baseline scores on the EDSS for sustained progression of disability and the number of relapses in the previous year for the relapse rate. Additional baseline factors were tested for inclusion in each of the models, including the EDSS score (≤3.5 or >3.5), the presence or absence of lesions as detected by gadolinium-enhanced MRI, the number of hyperintense lesions as detected by T2-weighted MRI (<9 or ≥9), and age (<40 or ≥40 years).21-23 Each covariate was tested in the model for statistical significance with the use of a backward-selection procedure, and only statistically significant covariates (P≤0.10) were included in the model. Only age was included in the final model for disability progression; the EDSS score, the presence or absence of lesions as detected by gadolinium-enhanced MRI, and age were included for the rate of relapse.
For the progression of disability, a sensitivity analysis was conducted on the change in EDSS scores that was sustained for 24 weeks. For the annualized relapse rate, sensitivity analyses were performed with and without censoring, as well as with and without adjustment for significant covariates. The unadjusted relapse rate was calculated as the total number of relapses divided by the total number of patient-years followed for each treatment group. The Hochberg procedure24 for multiple comparisons was used for the analysis of the two primary end points (the annualized relapse rate and the time to sustained progression of disability). Hence, the significance level was set so that if the higher of the P values for the analyses of these end points was ≤0.05, then both end points were considered to be statistically significant; otherwise, the lower of the P values was tested at a significance level of 0.025.
Secondary efficacy end points were rank-ordered, and a closed testing procedure was used, so that if statistical significance was not achieved for an end point, end points of a lower rank were not considered to be statistically significant. Secondary efficacy end points were analyzed by logistic regression that included a term for the treatment group and the respective baseline measure as a covariate. In the analyses of secondary end points, missing values were imputed using the mean for the respective measures in the study population.
Differences between treatment groups with regard to adverse events were analyzed by the chi-square test, and serious adverse events were analyzed by Fisher's exact test. Poisson regression was used to calculate the difference between the rates of infection in each treatment group.
All analyses followed the intention-to-treat principle. All reported P values are two-tailed. The one-year analyses occurred when 900 patient-years of data had been collected. The date on which the database was locked for the two-year analyses was January 31, 2005, which resulted in 2076 patient-years of observation and 1338 patient-years of exposure to natalizumab.
Results
Study Population
Among the 942 patients, 627 were assigned to receive natalizumab and 315 to receive placebo. There were no significant differences in baseline characteristics between the treatment groups (Table 1Table 1
Baseline Characteristics of the Patients.). A total of 856 patients (91 percent) completed the 120-week study (Figure 1Figure 1Patient Enrollment.), and 83 patients (a total of 9 percent, including 8 percent of patients in the natalizumab group and 10 percent of those in the placebo group) withdrew from the study. Thirty-nine patients discontinued the study drug but completed follow-up (a total of 4 percent, including 4 percent of patients in the natalizumab group and 5 percent of those in the placebo group). Three patients who were assigned to receive placebo were never treated; these patients were included in the intention-to-treat efficacy analyses but were excluded from the safety analyses.Efficacy
A sustained progression of disability over two years (the two-year primary end point) was significantly less likely in the natalizumab group than in the placebo group (Figure 2Figure 2
Kaplan–Meier Plots of the Time to Sustained Progression of Disability among Patients Receiving Natalizumab, as Compared with Placebo.). At two years, the cumulative probability of progression (on the basis of Kaplan–Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001), which represents a decrease of 12 percentage points or a relative 42 percent decrease in the risk of a sustained progression of disability with natalizumab (Table 2Table 2
End Points as Determined by Clinical Results and MRI Evaluation.). The sensitivity analysis of progression of disability that was sustained for 24 weeks yielded a 54 percent risk reduction in the natalizumab group (hazard ratio, 0.46; 95 percent confidence interval, 0.33 to 0.64; P<0.001).After one year of treatment, natalizumab reduced the annualized rate of relapse to 0.26 relapse per year, as compared with 0.81 relapse per year in the placebo group (P<0.001) (Table 2). The 68 percent relative reduction in the annualized rate of relapse produced by natalizumab was maintained at two years (P<0.001). Subgroup and sensitivity analyses showed results consistent with the primary analysis. The proportion of relapse-free patients was significantly higher in the natalizumab group than in the placebo group at one year (77 percent vs. 56 percent, P<0.001) and at two years (67 percent vs. 41 percent, P<0.001). Natalizumab reduced the risk of relapse over two years by 59 percent (hazard ratio, 0.41; 95 percent confidence interval, 0.34 to 0.51; P<0.001). An analysis of relapse in 51 patients in the natalizumab group and 27 patients in the placebo group who discontinued the study drug showed a return to baseline disease activity when natalizumab therapy was stopped but no evidence of rebound; 25 relapses were reported by 15 patients in the natalizumab group (29 percent) after discontinuation of the study medication, as compared with 13 relapses reported by 8 patients in the placebo group (30 percent), giving an annualized relapse rate of 0.495 for patients receiving natalizumab, as compared with a rate of 0.608 for those receiving placebo (data not shown).
Natalizumab reduced the mean number of new or enlarging hyperintense lesions detected by T2-weighted MRI over two years by 83 percent, as compared with placebo (P<0.001) (Table 2). Over two years, no new or enlarging hyperintense lesions developed in 57 percent of patients in the natalizumab group, as compared with 15 percent of patients in the placebo group. In contrast, 68 percent of patients in the placebo group had at least three new or enlarging hyperintense lesions, as compared with only 18 percent of patients in the natalizumab group. Natalizumab reduced the mean number of lesions as detected by gadolinium-enhanced MRI by 92 percent as compared with placebo at both one year and two years (P<0.001) (Table 2). In addition, lesions detected by gadolinium-enhanced MRI were absent in 97 percent of patients in the natalizumab group as compared with 72 percent of patients in the placebo group on MRI scanning at two years.
Safety
Over the course of the two-year study, 596 patients receiving natalizumab (95 percent) and 300 of the 312 patients receiving placebo (96 percent) reported at least one adverse event. As shown in Table 3Table 3
Adverse Events., adverse events that were significantly more common in the natalizumab group were fatigue and allergic reaction. The most severe adverse events reported by patients were mild in 17 percent, moderate in 55 percent, and severe in 23 percent of patients in the natalizumab group and mild in 13 percent, moderate in 56 percent, and severe in 27 percent in the placebo group. Serious adverse events were observed in 19 percent of patients receiving natalizumab and in 24 percent of patients receiving placebo (P=0.06); the most common serious adverse events were relapsing multiple sclerosis (6 percent with natalizumab and 13 percent with placebo; P<0.001), cholelithiasis (<1 percent with natalizumab and <1 percent with placebo), and the need for rehabilitation therapy (<1 percent with natalizumab and <1 percent with placebo). Two deaths occurred during the study, both in the natalizumab group. One patient, who died of malignant melanoma, had a history of malignant melanoma and had noted a new lesion at the time of receiving the first dose of natalizumab; he had received a total of five doses of natalizumab before receiving a confirmed diagnosis. A second patient died of alcohol intoxication after having received 25 doses of natalizumab.Infections were generally mild to moderate in severity and did not lead to drug discontinuation. The overall incidence of infection was 79 percent in each treatment group and occurred at a rate of 1 per patient-year in each group. When the rate was reanalyzed to include multiple occurrences of infection, it went up in each group, as expected. However, there remained no significant differences between the groups, with infections occurring at a rate of 1.52 per patient-year in the natalizumab group and 1.42 per patient-year in the placebo group (P=0.32). Common infections were nasopharyngitis (32 percent of patients receiving natalizumab and 33 percent of patients receiving placebo), influenza (17 percent and 16 percent, respectively), upper respiratory tract viral infection (13 percent and 15 percent), urinary tract infection not otherwise specified (13 percent and 12 percent), upper respiratory tract infection not otherwise specified (13 percent and 11 percent), and pharyngitis (12 percent and 10 percent). Serious infections occurred in 3.2 percent of patients receiving natalizumab and in 2.6 percent of patients receiving placebo. In the natalizumab group, the serious infections included four cases of pneumonia and five cases of urinary tract infection or urosepsis; the remaining infections that were reported as serious were of various causes and included pilonidal cyst infection, cellulitis, febrile infection, gastroenteritis, cryptosporidial diarrhea, mononucleosis, osteomyelitis, sinusitis, tonsillitis, viral infection, appendicitis, and an infection of unclear cause. In the placebo group, serious infections included two cases of appendicitis, two cases of gastroenteritis, and one case each of infection not otherwise specified, bladder infection, cystitis, and influenza.
A total of six cases of cancer were reported — one case (<1 percent) in the placebo group and five cases (<1 percent) in the natalizumab group. The five cases of cancer that occurred in natalizumab-treated patients included three cases of breast cancer, one case of stage 0 cervical cancer, and one case of newly diagnosed metastatic melanoma. There was one case of basal-cell carcinoma in the placebo group.
Infusion reactions were defined as any event that occurred within two hours after the start of the one-hour infusion; they were reported in 148 patients receiving natalizumab (24 percent) and in 55 patients receiving placebo (18 percent) (P=0.04). The most common infusion reaction was headache (5 percent with natalizumab and 3 percent with placebo). Most reactions were treated symptomatically and did not result in discontinuation of the study drug. Hypersensitivity reactions were defined as reports of hypersensitivity, allergic reaction, or anaphylactic or anaphylactoid reaction by the investigator, as well as any report of urticaria, allergic dermatitis, or hives. The category was determined by the investigator on the basis of clinical judgment and severity. Twenty-five patients receiving natalizumab (4 percent) had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphylactic or anaphylactoid reactions (urticaria plus other signs). One patient with a hypersensitivity reaction during the 7th infusion received other doses according to schedule and had an anaphylactic or anaphylactoid reaction during the 13th infusion. Fifteen reactions occurred on the second infusion. Eight hypersensitivity reactions (1.3 percent) were reported as serious adverse events among all patients receiving natalizumab, of which 5 reactions (0.8 percent) were considered serious systemic reactions (i.e., anaphylactic or anaphylactoid reactions). Per protocol, the study drug was to be discontinued in all patients who had hypersensitivity reactions. Five of the eight patients with serious adverse events had respiratory or chest symptoms, but only one patient required supplemental oxygen. No cardiovascular compromise was associated with any of these events, although one patient did receive epinephrine. All patients recovered without sequelae.
Because of adverse effects, 6 percent of the patients receiving natalizumab and 4 percent of those receiving placebo discontinued the study drug, and 3 percent of patients receiving natalizumab and 2 percent receiving placebo withdrew from the study. There were no significant differences between treatment groups in the proportions of patients with clinically notable changes in laboratory values. Increases in the number of lymphocytes, monocytes, eosinophils, and basophils were seen in natalizumab-treated patients without elevations in the number of neutrophils. These increases are consistent with expression of α4β1 on these white-cell subgroups and are a known pharmacodynamic effect of natalizumab. Increases in nucleated red cells were also seen transiently in a small number of patients. All changes were reversible, were without clinical effects, and returned to baseline levels, usually within 16 weeks after the last dose was administered.
Immunogenicity
Fifty-seven patients receiving natalizumab (9 percent) had detectable antibodies at some time during the study. Of these 57 patients, persistent antibodies to natalizumab (antibodies detected at ≥2 times that were ≥42 days apart) developed in 37 patients (6 percent), who also had an increase in infusion-related adverse events and a loss of efficacy of natalizumab.
Discussion
The results of AFFIRM support the hypothesis that the interaction between α4β1 integrin and its targets is an important component of inflammation of the central nervous system in multiple sclerosis and that the disruption of these interactions and the resultant attenuation of inflammation are beneficial to patients. In patients with relapsing multiple sclerosis, natalizumab significantly reduced the risk of progression of disability and the annualized rate of relapse over two years of treatment. The effect of natalizumab was rapid in onset and was sustained. In addition, efficacy was observed in terms of all secondary end points (an 83 percent reduction in the number of lesions as detected by T2-weighted MRI and a 92 percent reduction in the number of lesions as detected by gadolinium-enhanced MRI) and all sensitivity analyses of the primary end points, indicating the robustness of the result.
Disease-modifying therapies have become the cornerstone of treatment for patients with relapsing multiple sclerosis. The two-year registration trials of the therapies that are currently available (interferon beta products and glatiramer acetate) have shown that these agents reduce the annualized rate of relapse by about one third.13-16 In addition, neither interferon beta-1b nor glatiramer acetate had statistically significant effects on the progression of disability in patients with relapsing disease.14,15 Hence, there remains a need for more effective treatments for relapsing multiple sclerosis. The results of this study suggest that natalizumab may offer greater benefit to patients with relapsing multiple sclerosis than the other therapies.
The data presented here represent 30 percent of the placebo-controlled experience (patient-years of exposure) with natalizumab in patients with multiple sclerosis or Crohn's disease and 48 percent of the experience with natalizumab in patients with multiple sclerosis. In our study, natalizumab was safe as monotherapy over two years. In February 2005, all administration of natalizumab was voluntarily suspended by the manufacturers when they were notified of two cases of progressive multifocal leukoencephalopathy (PML). Both patients had received more than two years of natalizumab in combination with interferon beta-1a in a separate trial. Later, an additional case of PML was identified in a patient with Crohn's disease who had previously received a mistaken diagnosis of astrocytoma. The patient had received eight infusions of natalizumab. Detailed case histories of these three patients have been published elsewhere.25-27 An extensive safety evaluation of patients who received natalizumab in a clinical trial, also reported in this issue of the Journal, found no new confirmed cases of PML in patients treated with natalizumab.28 (The results of another clinical trial of natalizumab — in this case, administered with interferon beta-1a — also appear in this issue.29)
In conclusion, our study provides evidence that natalizumab significantly reduces the progression of disability and the occurrence of clinical relapse and suppresses the formation of lesions as visualized by MRI in patients with relapsing multiple sclerosis. Moreover, our data indicate that efficacy is realized early and persists throughout the treatment period. Within the 30-month evaluation period of this trial, natalizumab monotherapy had an excellent safety and tolerability profile. Continued assessments of long-term treatment with natalizumab will better define the safety profile of this effective therapy and establish its place in the arsenal of treatments for relapsing multiple sclerosis.
Supported by Biogen Idec and Elan Pharmaceuticals. Data were analyzed by Biogen Idec and Elan Pharmaceuticals.
Dr. Polman reports having received consulting fees from Biogen Idec, Schering, Teva, Serono, Novartis, GlaxoSmithKline, and Antisense Therapeutics; lecture fees from Biogen Idec, Schering, and Teva; and grant support from Biogen Idec and Schering, Wyeth, and GlaxoSmithKline. Dr. O'Connor reports having received consulting fees from Biogen Idec, Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Serono, Schering, and Wyeth; lecture fees from Biogen Idec; and grant support from Biogen Idec, Novartis, Sanofi-Aventis, Schering, BioMS, Bristol-Myers Squibb, and Genentech. Dr. Havrdova reports having received consulting fees from Biogen Idec and Serono and lecture fees from Schering, Biogen Idec, Serono, and Teva. Dr. Hutchinson reports having received consulting fees from Biogen Idec; lecture fees from Serono, Schering, and Biogen Idec; and grant support from Serono, Schering, and Biogen Idec. Dr. Kappos reports having received grant support from Biogen Idec, Schering, Wyeth, Novartis, Serono, Teva, Sanofi-Aventis, and GlaxoSmithKline. Dr. Miller reports having received consulting fees from Biogen Idec, Wyeth, Novartis, UCB Pharma, and Bristol-Myers Squibb; lecture fees from Biogen Idec and Serono; and grant support from Biogen Idec, GlaxoSmithKline, and Schering. Dr. Phillips reports having received consulting fees from Biogen Idec, Teva, and Genzyme and lecture fees from Biogen Idec. Dr. Lublin reports having received grant support from Biogen Idec, Teva, Acorda, and Merck and consulting and lecture fees from Biogen Idec, Berlex, Teva, Novartis, Schering-Plough, Serono, Pfizer, Amgen, and Antisense Therapeutics. Dr. Giovannoni reports having received consulting fees from Biogen Idec, Serono, Teva, and Schering; lecture fees from Biogen Idec, Serono, Teva, and Schering; and grant support from Biogen Idec, GlaxoSmithKline, and Teva. Dr. Toal reports having formerly been employed by Biogen Idec. Ms. Lynn, Dr. Panzara, and Dr. Sandrock report having equity interests in and being employed by Biogen Idec. No other potential conflict of interest relevant to this article was reported.
We are indebted to Nancy Bormann for her editorial assistance.
Source Information
From the Vrije Universiteit Medical Center, Amsterdam (C.H.P.); St. Michael's Hospital, Toronto (P.W.O.); General Teaching Hospital, Prague, Czech Republic (E.H.); St. Vincent's University Hospital, Dublin, Ireland (M.H.); University Hospital Basel, Basel, Switzerland (L.K.); Institute of Neurology, London (D.H.M., G.G.); Texas Neurology, Dallas (J.T.P.); Mt. Sinai School of Medicine, New York (F.D.L.); Silesian Medical University, Katowice, Poland (A.W.); and Biogen Idec, Cambridge, Mass. (M.T., F.L., M.A.P., A.W.S.).
Address reprint requests to Dr. Polman at the VU Medical Center, P.O. Box 7057, Amsterdam 1007 MB, the Netherlands, or at ch.polman@vumc.nl.
Additional members of the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study group are listed in the Supplementary Appendix, available with the full text of this article at www.nejm.org.
- References
References
1
Ffrench-Constant C . Pathogenesis of multiple sclerosis. Lancet 1994;343:271-275
CrossRef | Web of Science | Medline2
Hemler ME ,Sanchez-Madrid F ,Flotte TJ , et al. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. J Immunol 1984;132:3011-3018
Web of Science | Medline3
Lobb RR ,Hemler ME . The pathophysiologic role of alpha 4 integrins in vivo. J Clin Invest 1994;94:1722-1728
CrossRef | Web of Science | Medline4
Baron JL ,Madri JA ,Ruddle NH ,Hashim G ,Janeway CA Jr . Surface expression of α4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 1993;177:57-68
CrossRef | Web of Science | Medline5
Elices MJ ,Osborn L ,Takada Y , et al. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 1990;60:577-584
CrossRef | Web of Science | Medline6
Carlos TM ,Schwartz BR ,Kovach NL , et al. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 1990;76:965-970[Erratum, Blood 1990;76:2420.]
Web of Science | Medline7
Bayless KJ ,Meininger GA ,Scholtz JM ,Davis GE . Osteopontin is a ligand for the α4β1 integrin. J Cell Sci 1998;111:1165-1174
Web of Science | Medline8
Davis LS ,Oppenheimer-Marks N ,Bednarczyk JL ,McIntyre BW ,Lipsky PE . Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules. J Immunol 1990;145:785-793
Web of Science | Medline9
Chan PY ,Aruffo A . VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin. J Biol Chem 1993;268:24655-24664
Web of Science | Medline10
O'Regan AW ,Chupp GL ,Lowry JA ,Goetschkes M ,Mulligan N ,Berman JS . Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro. J Immunol 1999;162:1024-1031
Web of Science | Medline11
Chabas D ,Baranzini SE ,Mitchell D , et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 2001;294:1731-1735
CrossRef | Web of Science | Medline12
Yednock TA ,Cannon C ,Fritz LC ,Sanchez-Madrid F ,Steinman L ,Karin N . Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin. Nature 1992;356:63-66
CrossRef | Web of Science | Medline13
Jacobs LD ,Cookfair DL ,Rudick RA , et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996;39:285-294[Erratum, Ann Neurol 1996;40:480.]
CrossRef | Web of Science | Medline14
The IFNB Multiple Sclerosis Study Group
Web of Science | Medline15
Johnson KP ,Brooks BR ,Cohen JA , et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 1995;45:1268-1276
Web of Science | Medline16
PRISMS (Prevention of Relapses and Disability by Interferon (beta)-1a Subcutaneously in Multiple Sclerosis) Study Group
CrossRef | Web of Science | Medline17
Miller DH ,Khan OA ,Sheremata WA , et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003;348:15-23
Full Text | Web of Science | Medline18
McDonald WI ,Compston A ,Edan G , et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50:121-127
CrossRef | Web of Science | Medline19
Kurtzke JF . Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444-1452
Web of Science | Medline20
Lublin FD ,Reingold SC . Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996;46:907-911
Web of Science | Medline21
Jacobs LD ,Beck RW ,Simon JH , et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000;343:898-904
Full Text | Web of Science | Medline22
Beck RW ,Chandler DL ,Cole SR , et al. Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol 2002;51:481-490
CrossRef | Web of Science | Medline23
Weinshenker BG ,Bass B ,Rice GPA , et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain 1989;112:133-146
CrossRef | Web of Science | Medline24
Hochberg Y . A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988;75:800-802
CrossRef | Web of Science25
Kleinschmidt-DeMasters BK ,Tyler KL . Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005;353:369-74
Full Text | Web of Science | Medline26
Langer-Gould A ,Atlas SW ,Green AJ ,Bollen AW ,Pelletier D . Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005;353:375-381
Full Text | Web of Science | Medline27
Van Assche G ,Van Ranst M ,Sciot R , et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 2005;353:362-368
Full Text | Web of Science | Medline28
Yousry TA ,Major EO ,Ryschkewitsch C , et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2006;354:924-933
Full Text | Web of Science | Medline29
Rudick RA ,Stuart WH ,Calabresi PA , et al. A randomized, placebo-controlled trial of natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006;354:911-923
Full Text | Web of Science | Medline
- Citing Articles (463)
Citing Articles
1
O. Fernández, C. Oreja-Guevara, R. Arroyo, G. Izquierdo, J. L. Pérez, X. Montalban. (2012) Natalizumab treatment of multiple sclerosis in Spain: results of an extensive observational study. Journal of Neurology
CrossRef2
F. Waldron-Lynch, O. Henegariu, S. Deng, P. Preston-Hurlburt, J. Tooley, R. Flavell, K. C. Herold. (2012) Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 4:118, 118ra12-118ra12
CrossRef3
Lawrence Steinman, Joan T Merrill, Iain B McInnes, Mark Peakman. (2012) Optimization of current and future therapy for autoimmune diseases. Nature Medicine 18:1, 59-65
CrossRef4
Fred D. Lublin. (2012) Disease activity free status in MS. Multiple Sclerosis and Related Disorders 1:1, 6-7
CrossRef5
Maria Chiara G Monaco, Eugene O Major. (2012) The link between VLA-4 and JC virus reactivation. Expert Review of Clinical Immunology 8:1, 63-72
CrossRef6
Anne Waschbisch, Tobias Derfuss. (2012) Placebo-controlled trials in relapsing–remitting multiple sclerosis: are they still needed?. Future Neurology 7:1, 37-44
CrossRef7
Henrik Gensicke, David Leppert, Özgür Yaldizli, Raija L.P. Lindberg, Matthias Mehling, Ludwig Kappos, Jens Kuhle. (2012) Monoclonal Antibodies and Recombinant Immunoglobulins for the Treatment of Multiple Sclerosis. CNS Drugs 26:1, 11-37
CrossRef8
David Baker, Gareth Pryce, Samuel J. Jackson, Chris Bolton, Gavin Giovannoni. (2012) The biology that underpins the therapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis. Multiple Sclerosis and Related Disorders
CrossRef9
Alexandre Prat, Olaf Stüve. (2012) Firategrast—natalizumab in a pill?. The Lancet Neurology
CrossRef10
David H Miller, Thomas Weber, Richard Grove, Claire Wardell, Joseph Horrigan, Ole Graff, Gillian Atkinson, Pinky Dua, Tarek Yousry, David MacManus, Xavier Montalban. (2012) Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebo-controlled trial. The Lancet Neurology
CrossRef11
Vishesh Chhibber, Robert Weinstein. (2012) Evidence-Based Review of Therapeutic Plasma Exchange in Neurological Disorders. Seminars in Dialysisno-no
CrossRef12
J. Río, M. Tintoré, J. Sastre-Garriga, C. Nos, J. Castilló, C. Tur, M. Comabella, X. Montalban. (2012) Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response. European Journal of Neurologyno-no
CrossRef13
Shiv Saidha, Christopher Eckstein, Peter A. Calabresi. (2012) New and emerging disease modifying therapies for multiple sclerosis. Annals of the New York Academy of Sciencesno-no
CrossRef14
Malou H. J. Fanchamps, Henrik Gensicke, Jens Kuhle, Ludwig Kappos, John H. J. Allum, Özgür Yaldizli. (2011) Screening for balance disorders in mildly affected multiple sclerosis patients. Journal of Neurology
CrossRef15
A. Melin, O. Outteryck, N. Collongues, H. Zéphir, M. C. Fleury, F. Blanc, A. Lacour, J. C. Ongagna, A. S. Berteloot, P. Vermersch, J. Sèze. (2011) Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis. Journal of Neurology
CrossRef16
Pietro Iaffaldano, Guglielmo Lucchese, Maria Trojano. (2011) Treating multiple sclerosis with natalizumab. Expert Review of Neurotherapeutics 11:12, 1683-1692
CrossRef17
Alan M. Palmer. (2011) Immunomodulatory medicines for multiple sclerosis: Progress and prospects. Drug Development Research 72:8, 664-673
CrossRef18
Per Soelberg Sørensen. (2011) Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis. Journal of the Neurological Sciences 311, S29-S34
CrossRef19
Xavier Montalban. (2011) Review of methodological issues of clinical trials in multiple sclerosis. Journal of the Neurological Sciences 311, S35-S42
CrossRef20
V. Rothhammer, S. Heink, F. Petermann, R. Srivastava, M. C. Claussen, B. Hemmer, T. Korn. (2011) Th17 lymphocytes traffic to the central nervous system independently of 4 integrin expression during EAE. Journal of Experimental Medicine 208:12, 2465-2476
CrossRef21
Imke Metz, Ernst-Wilhelm Radue, Agustin Oterino, Tania Kümpfel, Heinz Wiendl, Sven Schippling, Jens Kuhle, Mohammad Ali Sahraian, Francoise Gray, Veronika Jakl, Darius Häusler, Wolfgang Brück. (2011) Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy. Acta Neuropathologica
CrossRef22
T. W. West, J. Killestein, R. J. Fox. (2011) Natalizumab discontinuation: an increasingly tricky proposition. European Journal of Neurologyno-no
CrossRef23
Miklos Banati, Zsolt Hosszu, Anita Trauninger, Laszlo Szereday, Zsolt Illes. (2011) Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease. Muscle & Nerve 44:5, 720-726
CrossRef24
Joep Killestein, Richard A Rudick, Chris H Polman. (2011) Oral treatment for multiple sclerosis. The Lancet Neurology 10:11, 1026-1034
CrossRef25
S. Bresch, M. Cohen, F. Rocher, M. Laffon, P. Thomas, C. Lebrun. (2011) Anomalies hématologiques du natalizumab et sa signification clinique. Revue Neurologique
CrossRef26
R. Lanzillo, M. Quarantelli, S. Bonavita, G. Ventrella, G. Lus, G. Vacca, A. Prinster, G. Orefice, G. Tedeschi, V. Brescia Morra. (2011) Natalizumab vs interferon beta 1a in relapsing-remitting multiple sclerosis: a head-to-head retrospective study. Acta Neurologica Scandinavicano-no
CrossRef27
Fatima Alnaimat, Paramvir Sidhu, Sujata Sarkar. (2011) T-cell targeted therapies in autoimmune diseases. Drug Development Research 72:7, 585-597
CrossRef28
Oscar Fernández. (2011) Nuevos fármacos para el tratamiento de la esclerosis múltiple. FMC - Formación Médica Continuada en Atención Primaria 18:9, 582-588
CrossRef29
Corinna Trebst, Peter Raab, Elke Verena Voss, Paulus Rommer, Mazen Abu-Mugheisib, Uwe K. Zettl, Martin Stangel. (2011) Longitudinal extensive transverse myelitis—it's not all neuromyelitis optica. Nature Reviews Neurology
CrossRef30
O. Fernández, J.A. García-Merino, R. Arroyo, J.C. Álvarez-Cermeño, T. Arbizu, G. Izquierdo, A. Saiz, J.Olascoaga, A. Rodríguez-Antigüedad, J.M. Prieto, C. Oreja-Guevara, M.A. Hernández, X. Montalbán. (2011) Consenso español sobre la utilización de natalizumab (Tysabri®) - 2011. Neurología
CrossRef31
Gilles Defer, Delphine Mariotte, Nathalie Derache, Olivier Toutirais, Hélène Legros, Brigitte Cauquelin, Brigitte Le Mauff. (2011) CD49d expression as a promising biomarker to monitor natalizumab efficacy. Journal of the Neurological Sciences
CrossRef32
K. Ghoreschi, J. Bruck, C. Kellerer, C. Deng, H. Peng, O. Rothfuss, R. Z. Hussain, A. R. Gocke, A. Respa, I. Glocova, N. Valtcheva, E. Alexander, S. Feil, R. Feil, K. Schulze-Osthoff, R. A. Rupec, A. E. Lovett-Racke, R. Dringen, M. K. Racke, M. Rocken. (2011) Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. Journal of Experimental Medicine 208:11, 2291-2303
CrossRef33
Bianca Weinstock-Guttman, Steven L. Galetta, Gavin Giovannoni, Eva Havrdova, Michael Hutchinson, Ludwig Kappos, Paul W. O’Connor, J. Theodore Phillips, Chris Polman, William H. Stuart, Frances Lynn, Christophe Hotermans. (2011) Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS. Journal of Neurology
CrossRef34
O'Connor, Paul, Wolinsky, Jerry S., Confavreux, Christian, Comi, Giancarlo, Kappos, Ludwig, Olsson, Tomas P., Benzerdjeb, Hadj, Truffinet, Philippe, Wang, Lin, Miller, Aaron, Freedman, Mark S., . (2011) Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis. New England Journal of Medicine 365:14, 1293-1303
Full Text35
Eugenio Pucci, Giorgio Giuliani, Alessandra Solari, Silvana Simi, Silvia Minozzi, Carlo Di Pietrantonj, Ian Galea, Eugenio Pucci. 2011. Natalizumab for relapsing remitting multiple sclerosis. .
CrossRef36
A. Bayas, J. Penzien, K. Hellwig. (2011) Accidental natalizumab administration to the third trimester of pregnancy in an adolescent patient with multiple sclerosis. Acta Neurologica Scandinavica 124:4, 290-292
CrossRef37
Brian Healy, Tanuja Chitnis, David Engler. (2011) Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies. Journal of Neurology 258:10, 1812-1819
CrossRef38
Dorothea Buck, Bernhard Hemmer. (2011) Treatment of multiple sclerosis: current concepts and future perspectives. Journal of Neurology 258:10, 1747-1762
CrossRef39
Manuel Comabella, Koen Vandenbroeck. (2011) Pharmacogenomics and Multiple Sclerosis: Moving Toward Individualized Medicine. Current Neurology and Neuroscience Reports 11:5, 484-491
CrossRef40
María José Magraner, Francisco Coret, Arantxa Navarré, Isabel Boscá, María Simó, Matilde Escutia, Ana Bernad, Laura Navarro, Bonaventura Casanova. (2011) Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study. Journal of Neurology 258:10, 1805-1811
CrossRef41
Sara Olofsson, Anne Wickström, Anna Häger Glenngård, Ulf Persson, Anders Svenningsson. (2011) Effect of Treatment with Natalizumab on Ability to Work in People with Multiple Sclerosis. BioDrugs 25:5, 299-306
CrossRef42
Ken O’Day, Kellie Meyer, Ross M. Miller, Sonalee Agarwal, Meg Franklin. (2011) Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis. Journal of Medical Economics 14:5, 617-627
CrossRef43
Jeremy Chataway, David H Miller. (2011) Multiple sclerosis—quenching the flames of inflammation. The Lancet
CrossRef44
Todd V. Cartee, Kellie J. White, Marvin Newton-West, Robert A. Swerlick. (2011) Hypoxia and hypoxia mimetics inhibit TNF-dependent VCAM1 induction in the 5A32 endothelial cell line via a hypoxia inducible factor dependent mechanism. Journal of Dermatological Science
CrossRef45
M P Rettig, G Ansstas, J F DiPersio. (2011) Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4. Leukemia
CrossRef46
Joachim Havla, Lisa Ann Gerdes, Ingrid Meinl, Markus Krumbholz, Hans Faber, Frank Weber, Hannah Luise Pellkofer, Reinhard Hohlfeld, Tania Kümpfel. (2011) De-escalation from natalizumab in multiple sclerosis: recurrence of disease activity despite switching to glatiramer acetate. Journal of Neurology 258:9, 1665-1669
CrossRef47
Stephen M Schaaf, David Pitt, Michael K Racke. (2011) What happens when natalizumab therapy is stopped?. Expert Review of Neurotherapeutics 11:9, 1247-1250
CrossRef48
Andrew F. Ducruet, E. Sander Connolly. (2011) Targeting Lymphocytes in Ischemic Stroke. World Neurosurgery 76:3-4, 212-214
CrossRef49
A. Kerbrat, E. Le Page, E. Leray, T. Anani, M. Coustans, C. Desormeaux, C. Guiziou, P. Kassiotis, F. Lallement, D. Laplaud, P. Diraison, F. Rouhart, E. Sartori, R. Wardi, S. Wiertlewski, G. Edan. (2011) Natalizumab and drug holiday in clinical practice: An observational study in very active relapsing remitting Multiple Sclerosis patients. Journal of the Neurological Sciences 308:1-2, 98-102
CrossRef50
E. J. Fox, H. C. Sullivan, S. K. Gazda, L. Mayer, L. O’Donnell, K. Melia, S. L. Lake. (2011) A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis. European Journal of Neurologyno-no
CrossRef51
Gillian M. Bell, Gary Reynolds, John D. Isaacs. (2011) Biologic therapies in non-rheumatic diseases: lessons for rheumatologists?. Nature Reviews Rheumatology 7:9, 507-516
CrossRef52
M. Mäurer, R. Dachsel, S. Domke, S. Ries, G. Reifschneider, A. Friedrich, P. Knorn, H. Landefeld, G. Niemczyk, P. Schicklmaier, C. Wernsdörfer, S. Windhagen, H. Albrecht, S. Schwab, . (2011) Health care situation of patients with relapsing-remitting multiple sclerosis receiving immunomodulatory therapy: a retrospective survey of more than 9000 German patients with MS. European Journal of Neurology 18:8, 1036-1045
CrossRef53
Per Soelberg Sorensen, Jan Lycke, Juha-Pekka Erälinna, Astrid Edland, Xingchen Wu, Jette Lautrup Frederiksen, Annette Oturai, Clas Malmeström, Egon Stenager, Finn Sellebjerg, Helle Bach Sondergaard. (2011) Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. The Lancet Neurology 10:8, 691-701
CrossRef54
B Mark Keegan. (2011) Natalizumab for multiple sclerosis: a complicated treatment. The Lancet Neurology 10:8, 677-678
CrossRef55
Ludwig Kappos, David Bates, Gilles Edan, Mefkûre Eraksoy, Antonio Garcia-Merino, Nikolaos Grigoriadis, Hans-Peter Hartung, Eva Havrdová, Jan Hillert, Reinhard Hohlfeld, Marcelo Kremenchutzky, Olivier Lyon-Caen, Ariel Miller, Carlo Pozzilli, Mads Ravnborg, Takahiko Saida, Christian Sindic, Karl Vass, David B Clifford, Stephen Hauser, Eugene O Major, Paul W O'Connor, Howard L Weiner, Michel Clanet, Ralf Gold, Hans H Hirsch, Ernst-Wilhelm Radü, Per Soelberg Sørensen, John King. (2011) Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. The Lancet Neurology 10:8, 745-758
CrossRef56
B. Singer, A. P. Ross, K. Tobias. (2011) Oral fingolimod for the treatment of patients with relapsing forms of multiple sclerosis. International Journal of Clinical Practice 65:8, 887-895
CrossRef57
Bernard M.J. Uitdehaag, Frederik Barkhof, Patricia K. Coyle, Jason D. Gardner, Douglas R. Jeffery, Daniel D. Mikol. (2011) The changing face of multiple sclerosis clinical trial populations. Current Medical Research and Opinion 27:8, 1529-1537
CrossRef58
Kerstin Hellwig, Sebastian Schimrigk, Andrew Chan, Jörg Epplen, Ralf Gold. (2011) A newborn with Pierre Robin sequence after preconceptional mitoxantrone exposure of a female with multiple sclerosis. Journal of the Neurological Sciences 307:1-2, 164-165
CrossRef59
Christine Lebrun, Patrick Vermersch, David Brassat, Gilles Defer, Lucien Rumbach, Pierre Clavelou, Marc Debouverie, Jérôme Seze, Sandrine Wiertlevsky, Olivier Heinzlef, Ayman Tourbah, Agnes Fromont, Marc Frenay. (2011) Cancer and multiple sclerosis in the era of disease-modifying treatments. Journal of Neurology 258:7, 1304-1311
CrossRef60
A. Horga, M. Tintoré. (2011) Natalizumab para la esclerosis múltiple remitente-recurrente. Neurología 26:6, 357-368
CrossRef61
Marion Brandis Brodkey, Aliza Bitton Ben-Zacharia, Jennifer Decker Reardon. (2011) Living Well with Multiple Sclerosis. AJN, American Journal of Nursing 111:7, 40-48
CrossRef62
Emily K. Rainey-Barger, Julie M. Rumble, Stephen J. Lalor, Nilufer Esen, Benjamin M. Segal, David N. Irani. (2011) The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system. Brain, Behavior, and Immunity 25:5, 922-931
CrossRef63
Esther V Hobson, Basil Sharrack. (2011) Emerging oral disease-modifying therapies in multiple sclerosis: a review of the latest clinical evidence. Clinical Investigation 1:7, 1049-1058
CrossRef64
Mario Skarica, Christopher Eckstein, Katharine A. Whartenby, Peter A. Calabresi. (2011) Novel mechanisms of immune modulation of natalizumab in multiple sclerosis patients. Journal of Neuroimmunology 235:1-2, 70-76
CrossRef65
Bernd C Kieseier, Heinz Wiendl, Hans-Peter Hartung, Verena-Isabell Leussink, Olaf Stüve. (2011) Risks and benefits of multiple sclerosis therapies: need for continual assessment?. Current Opinion in Neurology 24:3, 238-243
CrossRef66
B. Bailey. (2011) Disease-modifying drugs in multiple sclerosis: a review of expenditure in Ireland. Irish Journal of Medical Science 180:2, 337-341
CrossRef67
Jordi Río, Manuel Comabella, Xavier Montalban. (2011) Multiple sclerosis: current treatment algorithms. Current Opinion in Neurology 24:3, 230-237
CrossRef68
Megan Hyland, Richard A Rudick. (2011) Challenges to clinical trials in multiple sclerosis: outcome measures in the era of disease-modifying drugs. Current Opinion in Neurology 24:3, 255-261
CrossRef69
I. A. Hoevenaren, L. C. de Vries, R. J. P. Rijnders, F. K. Lotgering. (2011) Delivery of healthy babies after natalizumab use for multiple sclerosis: a report of two cases. Acta Neurologica Scandinavica 123:6, 430-433
CrossRef70
Naser Muja, Mikhal E. Cohen, Jiangyang Zhang, Heechul Kim, Assaf A. Gilad, Piotr Walczak, Tamir Ben-Hur, Jeff W.M. Bulte. (2011) Neural precursors exhibit distinctly different patterns of cell migration upon transplantation during either the acute or chronic phase of EAE: A serial MR imaging study. Magnetic Resonance in Medicine 65:6, 1738-1749
CrossRef71
James J. Marriott, Paul W. O’Connor. (2011) Definitions of Breakthrough Disease and Second-Line Agents. Neurologic Clinics 29:2, 411-422
CrossRef72
Bernd C. Kieseier, Olaf Stüve. (2011) A critical appraisal of treatment decisions in multiple sclerosis—old versus new. Nature Reviews Neurology 7:5, 255-262
CrossRef73
Mathieu Leclerc, Jean-FranÇois Lesesve, Baptiste Gaillard, Xavier Troussard, Ayman Tourbah, Marc Debouverie, Sylvie Daliphard, Alain Delmer. (2011) Binucleated lymphocytes in patients with multiple sclerosis treated with natalizumab. Leukemia & Lymphoma 52:5, 910-912
CrossRef74
Gregory F. Wu, Enrique Alvarez. (2011) The Immunopathophysiology of Multiple Sclerosis. Neurologic Clinics 29:2, 257-278
CrossRef75
Lawrence M. Samkoff, Andrew D. Goodman. (2011) Symptomatic Management in Multiple Sclerosis. Neurologic Clinics 29:2, 449-463
CrossRef76
Ruth Lyck, Roberta Martinelli. (2011) Mechanisms of T-cell migration across the BBB. Future Neurology 6:3, 375-388
CrossRef77
Martin Duddy, Aiden Haghikia, Eleonora Cocco, Christian Eggers, Jelena Drulovic, Olga Carmona, Helene Zéphir, Ralf Gold. (2011) Managing MS in a changing treatment landscape. Journal of Neurology 258:5, 728-739
CrossRef78
Andrea Harrer, Peter Wipfler, Max Einhaeupl, Georg Pilz, Katrin Oppermann, Wolfgang Hitzl, Shahrzad Afazel, Elisabeth Haschke-Becher, Peter Strasser, Eugen Trinka, Joerg Kraus. (2011) Natalizumab therapy decreases surface expression of both VLA-heterodimer subunits on peripheral blood mononuclear cells. Journal of Neuroimmunology 234:1-2, 148-154
CrossRef79
Kathleen Hawker. (2011) Progressive Multiple Sclerosis: Characteristics and Management. Neurologic Clinics 29:2, 423-434
CrossRef80
Ellen M. Mowry. (2011) Natural History of Multiple Sclerosis: Early Prognostic Factors. Neurologic Clinics 29:2, 279-292
CrossRef81
Catherine Larochelle, Jorge Ivan Alvarez, Alexandre Prat. (2011) How do immune cells overcome the blood–brain barrier in multiple sclerosis?. FEBS Letters
CrossRef82
Marina A. Lynch, Kingston H.G. Mills. (2011) Immunology meets neuroscience – Opportunities for immune intervention in neurodegenerative diseases. Brain, Behavior, and Immunity
CrossRef83
Michael Hecker, Peter Lorenz, Felix Steinbeck, Li Hong, Gabriela Riemekasten, Yixue Li, Uwe K. Zettl, Hans-Jürgen Thiesen. (2011) Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis. Autoimmunity Reviews
CrossRef84
C. Warnke, O. Adams, R. Gold, H.-P. Hartung, R. Hohlfeld, H. Wiendl, B.C. Kieseier. (2011) Progressive multifokale Leukenzephalopathie unter Natalizumab. Der Nervenarzt 82:4, 475-480
CrossRef85
Małgorzata Siger, Agnieszka Durko, Agnieszka Nicpan, Maria Konarska, Monika Grudziecka, Krzysztof Selmaj. (2011) Discontinuation of interferon beta therapy in multiple sclerosis patients with high pre-treatment disease activity leads to prompt return to previous disease activity. Journal of the Neurological Sciences 303:1-2, 50-52
CrossRef86
Robert C. Fuhlbrigge, Rafka Chaiban. (2011) The Immune System, the Skin, and Childhood Rheumatic Disease. Current Rheumatology Reports 13:2, 103-109
CrossRef87
, A. Ghezzi, L. M. E. Grimaldi, M. G. Marrosu, C. Pozzilli, G. Comi, A. Bertolotto, M. Trojano, P. Gallo, R. Capra, D. Centonze, E. Millefiorini, S. Sotgiu, V. Brescia Morra, M. P. Amato, A. Lugaresi, G. Mancardi, D. Caputo, E. Montanari, L. Provinciali, L. Durelli, R. Bergamaschi, P. Bellantonio, M. R. Tola, S. Cottone, G. Savettieri, G. Tedeschi. (2011) Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group—Italian Neurological Society. Neurological Sciences 32:2, 351-358
CrossRef88
Hans-Peter Hartung, Orhan Aktas. (2011) Evolution of multiple sclerosis treatment: next generation therapies meet next generation efficacy criteria. The Lancet Neurology 10:4, 293-295
CrossRef89
Gavin Giovannoni, Stuart Cook, Kottil Rammohan, Peter Rieckmann, Per Soelberg Sørensen, Patrick Vermersch, Anthony Hamlett, Vissia Viglietta, Steven Greenberg. (2011) Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis. The Lancet Neurology 10:4, 329-337
CrossRef90
Joep Killestein, Chris H. Polman. (2011) Determinants of interferon β efficacy in patients with multiple sclerosis. Nature Reviews Neurology 7:4, 221-228
CrossRef91
Daniel Harrison, Douglas E Gladstone. (2011) High-dose chemotherapy and multiple sclerosis. Current Opinion in Oncology 23:2, 221-226
CrossRef92
A. Liesz, W. Zhou, E. Mracsko, S. Karcher, H. Bauer, S. Schwarting, L. Sun, D. Bruder, S. Stegemann, A. Cerwenka, C. Sommer, A. H. Dalpke, R. Veltkamp. (2011) Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke. Brain 134:3, 704-720
CrossRef93
Joy Derwenskus. (2011) Current Disease-Modifying Treatment of Multiple Sclerosis. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 78:2, 161-175
CrossRef94
M.J. Fernández-Megía, B. Casanova, M.J. Magraner, I. Font-Noguera, J.L. Poveda-Andrés. (2011) Evaluación de la efectividad y la seguridad del natalizumab en el tratamiento de la esclerosis múltiple remitente recidivante. Farmacia Hospitalaria 35:2, 75-79
CrossRef95
Aaron E. Miller. (2011) Multiple Sclerosis: Where Will We Be in 2020?. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 78:2, 268-279
CrossRef96
Hans-Peter Hartung, Xavier Montalban, Per Soelberg Sorensen, Patrick Vermersch, Tomas Olsson. (2011) Principles of a new treatment algorithm in multiple sclerosis. Expert Review of Neurotherapeutics 11:3, 351-362
CrossRef97
Manuel Comabella, Samia J. Khoury. (2011) Immunopathogenesis of multiple sclerosis. Clinical Immunology
CrossRef98
Cris S Constantinescu, Nasr Farooqi, Kate O'Brien, Bruno Gran. (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British Journal of Pharmacologyno-no
CrossRef99
C. Kuhn, S. You, F. Valette, G. Hale, P. van Endert, J.-F. Bach, H. Waldmann, L. Chatenoud. (2011) Human CD3 Transgenic Mice: Preclinical Testing of Antibodies Promoting Immune Tolerance. Science Translational Medicine 3:68, 68ra10-68ra10
CrossRef100
G. Kooij, M. R. Mizee, J. van Horssen, A. Reijerkerk, M. E. Witte, J. A. R. Drexhage, S. M. A. van der Pol, B. van het Hof, G. Scheffer, R. Scheper, C. D. Dijkstra, P. van der Valk, H. E. de Vries. (2011) Adenosine triphosphate-binding cassette transporters mediate chemokine (C-C motif) ligand 2 secretion from reactive astrocytes: relevance to multiple sclerosis pathogenesis. Brain 134:2, 555-570
CrossRef101
Henry McFarland. (2011) The importance of clinical trials in unraveling the mysteries of multiple sclerosis. Journal of Neuroimmunology 231:1-2, 3-6
CrossRef102
Brandon A. Brown, Mina Torabi. (2011) Incidence of Infusion-Associated Reactions with Rituximab for Treating Multiple Sclerosis. Drug Safety 34:2, 117-123
CrossRef103
Lennart T. Mars, Philippe Saikali, Roland S. Liblau, Nathalie Arbour. (2011) Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiple sclerosis and its animal models. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1812:2, 151-161
CrossRef104
A. Laroni, M. Bedognetti, A. Uccelli, E. Capello, G. L. Mancardi. (2011) Association of melanoma and natalizumab therapy in the Italian MS population: a second case report. Neurological Sciences 32:1, 181-182
CrossRef105
S. Belachew, R. Phan-Ba, E. Bartholomé, V. Delvaux, I. Hansen, P. Calay, K. E. Hafsi, G. Moonen, L. Tshibanda, M. Vokaer. (2011) Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. European Journal of Neurology 18:2, 240-245
CrossRef106
Brenda Banwell, Amit Bar-Or, Gavin Giovannoni, Russell C. Dale, Marc Tardieu. (2011) Therapies for multiple sclerosis: considerations in the pediatric patient. Nature Reviews Neurology 7:2, 109-122
CrossRef107
Flavia Mattioli, C. Stampatori, R. Capra. (2011) The effect of natalizumab on cognitive function in patients with relapsing-remitting multiple sclerosis: preliminary results of a 1-year follow-up study. Neurological Sciences 32:1, 83-88
CrossRef108
Simon Eckermann, Michael Coory, Andrew R. Willan. (2011) Consistently Estimating Absolute Risk Difference when Translating Evidence to Jurisdictions of Interest. PharmacoEconomics 29:2, 87-96
CrossRef109
Elena Buccellato, Donatella Carretta, Aneli Utan, Chiara Cavina, Ester Speroni, Giampaolo Grassi, Sanzio Candeletti, Patrizia Romualdi. (2011) Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis. Journal of Ethnopharmacology 133:3, 1033-1038
CrossRef110
Ron Milo, Hillel Panitch. (2011) Combination therapy in multiple sclerosis. Journal of Neuroimmunology 231:1-2, 23-31
CrossRef111
Karen Schreiber, Per Soelberg Sorensen. (2011) Cladribine in the treatment of multiple sclerosis. Clinical Investigation 1:2, 317-326
CrossRef112
G. L. Mancardi, G. Tedeschi, M. P. Amato, R. D’Alessandro, F. Drago, C. Milanese, P. Popoli, P. Rossi, G. Savettieri, M. R. Tola, G. Comi, C. Pozzilli, A. Bertolotto, M. G. Marrosu, L. M. E. Grimaldi, A. Laroni, N. Vanacore, A. Covezzoli, M. Rosa, C. Piccinni, N. Montanaro, L. Periotto, R. Iommelli, C. Tomino, L. Provinciali. (2011) Three years of experience: the Italian registry and safety data update. Neurological Sciences 31:S3, 295-297
CrossRef113
F. Sangalli, L. Moiola, S. Bucello, P. Annovazzi, A. Rizzo, M. Radaelli, G. Vitello, L. M. E. Grimaldi, A. Ghezzi, V. Martinelli, G. Comi. (2011) Efficacy and tolerability of natalizumab in relapsing–remitting multiple sclerosis patients: a post-marketing observational study. Neurological Sciences 31:S3, 299-302
CrossRef114
Nancy L. Sicotte. (2011) Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications. Neurotherapeutics 8:1, 54-62
CrossRef115
Trygve Holmøy, Elisabeth Celius. (2011) Utvikling av ny behandling for multippel sklerose. Tidsskrift for Den norske legeforening 131:8, 832-836
CrossRef116
Murat Yildiz, Barbara Tettenborn, Norman Putzki. (2011) Multiple Sclerosis-Associated Fatigue during Disease-Modifying Treatment with Natalizumab, Interferon-Beta and Glatiramer Acetate. European Neurology 65:4, 231-232
CrossRef117
Michelle L. Apperson, Mark A. Agius. 2011. Clinical and Neuroimaging Assessments for Research Studies (Including Drug Trials) in Multiple Sclerosis. .
CrossRef118
Leyre Mestre, Paula M Iñigo, Miriam Mecha, Fernando G Correa, Miriam Hernangómez-Herrero, Frida Loría, Fabian Docagne, José Borrell, Carmen Guaza. (2011) Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and reduces leukocyte transmigration in a model of blood brain barrier by activation of CB1 receptors. Journal of Neuroinflammation 8:1, 102
CrossRef119
Ciro Florio, Giorgia Teresa Maniscalco. (2011) Improvement of visual acuity in patients with severe visual loss affected by multiple sclerosis treated with natalizumab: a case report. Neurological Sciences 31:S3, 325-327
CrossRef120
F. Mattioli, C. Stampatori, F. Bellomi, R. Capra. (2011) Natalizumab efficacy on cognitive impairment in MS. Neurological Sciences 31:S3, 321-323
CrossRef121
Ranjan Dutta, Bruce D. Trapp. (2011) Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Progress in Neurobiology 93:1, 1-12
CrossRef122
Fredrik Piehl, C. Holmén, J. Hillert, T. Olsson. (2011) Swedish natalizumab (Tysabri) multiple sclerosis surveillance study. Neurological Sciences 31:S3, 289-293
CrossRef123
Martin Gunnarsson, Clas Malmeström, Markus Axelsson, Peter Sundström, Charlotte Dahle, Magnus Vrethem, Tomas Olsson, Fredrik Piehl, Niklas Norgren, Lars Rosengren, Anders Svenningsson, Jan Lycke. (2011) Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Annals of Neurology 69:1, 83-89
CrossRef124
F. Rinaldi, M. Calabrese, D. Seppi, M. Puthenparampil, P. Perini, P. Gallo. (2011) Natalizumab prevents the accumulation of cortical lesions in relapsing remitting multiple sclerosis: a preliminary report. Neurological Sciences 31:S3, 317-320
CrossRef125
Peter Wipfler, Andrea Harrer, Georg Pilz, Katrin Oppermann, Eugen Trinka, Jörg Kraus. (2011) Recent developments in approved and oral multiple sclerosis treatment and an update on future treatment options. Drug Discovery Today 16:1-2, 8-21
CrossRef126
L. Prosperini, G. Borriello, F. Fubelli, F. Marinelli, Carlo Pozzilli. (2011) Natalizumab treatment in multiple sclerosis: the experience of S. Andrea MS Centre in Rome. Neurological Sciences 31:S3, 303-307
CrossRef127
Prakash Manikwar, Paul Kiptoo, Ahmed H. Badawi, Barlas Büyüktimkin, Teruna J. Siahaan. (2011) Antigen-specific blocking of CD4-specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Medicinal Research Reviewsn/a-n/a
CrossRef128
M. G. Marrosu, L. Lorefice, J. Frau, G. Coghe, G. Fenu, R. Piras, M. Melis, E. Cocco. (2011) The cohort of the multiple sclerosis center of Cagliari. Neurological Sciences 31:S3, 309-312
CrossRef129
M.J. Fernández-Megía, B. Casanova, M.J. Magraner, I. Font-Noguera, J.L. Poveda-Andrés. (2011) Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis. Farmacia Hospitalaria (English Edition) 35:2, 75-79
CrossRef130
Thomas P. Leist, Robert Weissert. (2011) Cladribine. Clinical Neuropharmacology 34:1, 28-35
CrossRef131
A. Horga, M. Tintoré. (2011) Natalizumab for relapsing-remitting multiple sclerosis. Neurología (English Edition) 26:6, 357-368
CrossRef132
Y. C. Wang, A. Sandrock, J. R. Richert, L. Meyerson, X. Miao. (2011) Short-Term Relapse Quantitation as a Fully Surrogate Endpoint for Long-Term Sustained Progression of Disability in RRMS Patients Treated with Natalizumab. Neurology Research International 2011, 1-6
CrossRef133
Amir-Hadi Maghzi, Aimee Borazanci, Jeanie McGee, J. Steven Alexander, Eduardo Gonzalez-Toledo, Alireza Minagar. 2011. Multiple SclerosisPathophysiology, Clinical Features, Diagnosis, and Management. , 1-23.
CrossRef134
Eileen M. O’Connor, Rae Ann Maxwell. 2011. Clinical Development and Benefit–Risk Profile of Natalizumab. , 167-191.
CrossRef135
Colleen E. Hayes, Faye E. Nashold, Christopher G. Mayne, Justin A. Spanier, Corwin D. Nelson. 2011. Vitamin D and Multiple Sclerosis. , 1843-1877.
CrossRef136
Arnd Heiligenhaus, Stephan Thurau, Maren Hennig, Rafael S. Grajewski, Gerhild Wildner. (2010) Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease. Graefe's Archive for Clinical and Experimental Ophthalmology 248:11, 1531-1551
CrossRef137
Volker Brinkmann, Andreas Billich, Thomas Baumruker, Peter Heining, Robert Schmouder, Gordon Francis, Shreeram Aradhye, Pascale Burtin. (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nature Reviews Drug Discovery 9:11, 883-897
CrossRef138
Giancarlo Comi. (2010) Effects of disease modifying treatments on cognitive dysfunction in multiple sclerosis. Neurological Sciences 31:S2, 261-264
CrossRef139
Eilhard Mix, Hans Meyer-Rienecker, Hans-Peter Hartung, Uwe K. Zettl. (2010) Animal models of multiple sclerosis—Potentials and limitations. Progress in Neurobiology 92:3, 386-404
CrossRef140
Clare J. Fowler, Catherine Dalton, Jalesh N. Panicker. (2010) Review of Neurologic Diseases for the Urologist. Urologic Clinics of North America 37:4, 517-526
CrossRef141
M. Filippi, M. A. Rocca, D. L. Arnold, R. Bakshi, F. Barkhof, N. De Stefano, F. Fazekas, E. Frohman, D. H. Miller, J. S. Wolinsky. 2010. Use of Imaging in Multiple Sclerosis. , 35-51.
CrossRef142
Dermot Cox, Marian Brennan, Niamh Moran. (2010) Integrins as therapeutic targets: lessons and opportunities. Nature Reviews Drug Discovery 9:10, 804-820
CrossRef143
Michael Hutchinson. (2010) Natalizumab Therapy of Multiple Sclerosis. Journal of Interferon & Cytokine Research 30:10, 787-789
CrossRef144
Peter Vanderslice, Darren G. Woodside, Amy R. Caivano, E. Radford Decker, Christy L. Munsch, Sidney J. Sherwood, Wanda S. LeJeune, Yuko J. Miyamoto, Bradley W. McIntyre, Ronald G. Tilton, Richard A.F. Dixon. (2010) Potent in vivo suppression of inflammation by selectively targeting the high affinity conformation of integrin α4β1. Biochemical and Biophysical Research Communications 400:4, 619-624
CrossRef145
D. T. Selewski, G. V. Shah, B. M. Segal, P. A. Rajdev, S. K. Mukherji. (2010) Natalizumab (Tysabri). American Journal of Neuroradiology 31:9, 1588-1590
CrossRef146
Rachel A. Farrell, Gavin Giovannoni. (2010) Current and Future Role of Interferon Beta in the Therapy of Multiple Sclerosis. Journal of Interferon & Cytokine Research 30:10, 715-726
CrossRef147
Pauline A. van Schouwenburg, Geertje M. Bartelds, Margreet H. Hart, Lucien Aarden, Gerrit Jan Wolbink, Diana Wouters. (2010) A novel method for the detection of antibodies to adalimumab in the presence of drug reveals “hidden” immunogenicity in rheumatoid arthritis patients. Journal of Immunological Methods 362:1-2, 82-88
CrossRef148
Caihong Wang, Elyse K. Hanly, Leroy W. Wheeler, Manreet Kaur, Keely G. McDonald, Rodney D. Newberry. (2010) Effect of α4β7 blockade on intestinal lymphocyte subsets and lymphoid tissue development. Inflammatory Bowel Diseases 16:10, 1751-1762
CrossRef149
Alban Millonig, Harald Hegen, Franziska Di Pauli, Rainer Ehling, Claudia Gneiss, Martina Hoelzl, Bettina Künz, Andreas Lutterotti, Dagmar Rudzki, Thomas Berger, Markus Reindl, Florian Deisenhammer. (2010) Natalizumab treatment reduces endothelial activity in MS patients. Journal of Neuroimmunology 227:1-2, 190-194
CrossRef150
Jin Nakahara, Sadakazu Aiso, Norihiro Suzuki. (2010) Autoimmune Versus Oligodendrogliopathy: The Pathogenesis of Multiple Sclerosis. Archivum Immunologiae et Therapiae Experimentalis 58:5, 325-333
CrossRef151
J. M. Fletcher, S. J. Lalor, C. M. Sweeney, N. Tubridy, K. H. G. Mills. (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clinical & Experimental Immunology 162:1, 1-11
CrossRef152
Correne A DeCarlo, Alberto Severini, Lutz Edler, Nicholas G Escott, Paul F Lambert, Marina Ulanova, Ingeborg Zehbe. (2010) IFN-κ, a novel type I IFN, is undetectable in HPV-positive human cervical keratinocytes. Laboratory Investigation 90:10, 1482-1491
CrossRef153
Richard A. Rudick, Paul W. O'Connor, Chris H. Polman, Andrew D. Goodman, Soma S. Ray, Nancy M. Griffith, Stephanie A. Jurgensen, Leonid Gorelik, Fiona Forrestal, Alfred W. Sandrock, Susan E. Goelz. (2010) Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Annals of Neurology 68:3, 304-310
CrossRef154
Timothy W. West, Bruce A.C. Cree. (2010) Natalizumab dosage suspension: Are we helping or hurting?. Annals of Neurology 68:3, 395-399
CrossRef155
Silvia N. Tenembaum. (2010) Therapy of multiple sclerosis in children and adolescents. Clinical Neurology and Neurosurgery 112:7, 633-640
CrossRef156
K. Rejdak, S. Jackson, G. Giovannoni. (2010) Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin 95:1, 79-104
CrossRef157
Joanne L. Jones, Alasdair J. Coles. (2010) New treatment strategies in multiple sclerosis. Experimental Neurology 225:1, 34-39
CrossRef158
Joep Killestein, Anke Vennegoor, Eva M. Strijbis, Alexandra Seewann, Bob W. van Oosten, Bernard M. J. Uitdehaag, Chris H. Polman. (2010) Natalizumab drug holiday in multiple sclerosis: Poorly Tolerated. Annals of Neurology 68:3, 392-395
CrossRef159
Norman Putzki, Oliver Stich, Kristina Gartzen, Oliver Kastrup, Barbara Tettenborn, Sebastian Rauer. (2010) LETTER TO THE EDITOR: Natalizumab treatment in paediatric multiple sclerosis: a case of induction, de-escalation and escalation. European Journal of Neurologyno-no
CrossRef160
Jochen C. Ulzheimer, Sven G. Meuth, Stefan Bittner, Christoph Kleinschnitz, Bernd C. Kieseier, Heinz Wiendl. (2010) Therapeutic Approaches to Multiple Sclerosis. BioDrugs 24:4, 249-274
CrossRef161
Alison M. Gizinski, David A. Fox, Sujata Sarkar. (2010) Co-stimulation and T cells as therapeutic targets. Best Practice & Research Clinical Rheumatology 24:4, 463-477
CrossRef162
Sreeram V Ramagopalan, Ruth Dobson, Ute C Meier, Gavin Giovannoni. (2010) Multiple sclerosis: risk factors, prodromes, and potential causal pathways. The Lancet Neurology 9:7, 727-739
CrossRef163
Christian Schütz, Mathias Oelke, Jonathan P Schneck, Andreas Mackensen, Martin Fleck. (2010) Killer artificial antigen-presenting cells: the synthetic embodiment of a ‘guided missile’. Immunotherapy 2:4, 539-550
CrossRef164
A. García Merino, O. Fernández, X. Montalbán, C. de Andrés, T. Arbizu. (2010) Documento de consenso de la Sociedad Española de Neurología sobre el uso de medicamentos en esclerosis múltiple: escalado terapéutico. Neurología 25:6, 378-390
CrossRef165
Silvia Rossi, Giorgio Bernardi, Diego Centonze. (2010) The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Experimental Neurology 224:1, 92-102
CrossRef166
C M Rice, E A Mallam, A L Whone, P Walsh, D J Brooks, N Kane, S R Butler, D I Marks, N J Scolding. (2010) Safety and Feasibility of Autologous Bone Marrow Cellular Therapy in Relapsing-Progressive Multiple Sclerosis. Clinical Pharmacology & Therapeutics 87:6, 679-685
CrossRef167
Michel Bilello, Neeti Suri, Jaroslaw Krejza, John H. Woo, Linda J. Bagley, Alexander C. Mamourian, Arastoo Vossough, James Y. Chen, Bradd R. Millian, Todd Mulderink, Clyde E. Markowitz, Elias R. Melhem. (2010) An Approach to Comparing Accuracies of Two Flair MR Sequences in the Detection of Multiple Sclerosis Lesions in the Brain in the Absence of Gold Standard. Academic Radiology 17:6, 686-695
CrossRef168
Andreas P Lysandropoulos, Renaud A Du Pasquier. (2010) Demyelination as a complication of new immunomodulatory treatments. Current Opinion in Neurology 23:3, 226-233
CrossRef169
Yolanda S. Kap, Jon D. Laman, Bert A. ‘t Hart. (2010) Experimental Autoimmune Encephalomyelitis in the Common Marmoset, a Bridge Between Rodent EAE and Multiple Sclerosis for Immunotherapy Development. Journal of Neuroimmune Pharmacology 5:2, 220-230
CrossRef170
M. Buttmann, H. Wiendl. (2010) Therapeutische monoklonale Antikörper in der Neurologie. Der Nervenarzt 81:6, 753-766
CrossRef171
Reza Vosoughi, Mark S. Freedman. (2010) Therapy of MS. Clinical Neurology and Neurosurgery 112:5, 365-385
CrossRef172
Gijs Kooij, Jack van Horssen, Elizabeth C.M. de Lange, Arie Reijerkerk, Susanne M.A. van der Pol, Bert van het Hof, Joost Drexhage, Anke Vennegoor, Joep Killestein, George Scheffer, Ruud Oerlemans, Rik Scheper, Paul van der Valk, Christine D. Dijkstra, Helga E. de Vries. (2010) T lymphocytes impair P-glycoprotein function during neuroinflammation. Journal of Autoimmunity 34:4, 416-425
CrossRef173
Saud A. Sadiq, Lauren M. Puccio, Edward W. A. Brydon. (2010) JCV detection in multiple sclerosis patients treated with natalizumab. Journal of Neurology 257:6, 954-958
CrossRef174
(2010) Oral Cladribine and Fingolimod for Relapsing Multiple Sclerosis. New England Journal of Medicine 362:18, 1738-1740
Full Text175
L. Steinman. (2010) Inverse vaccination, the opposite of Jenner’s concept, for therapy of autoimmunity. Journal of Internal Medicine 267:5, 441-451
CrossRef176
Jeffrey S. Miller, Edus H. Warren, Marcel R.M. van den Brink, Jerome Ritz, Warren D. Shlomchik, William J. Murphy, A. John Barrett, Hans Jochem Kolb, Sergio Giralt, Michael R. Bishop, Bruce R. Blazar, J.H. Frederik Falkenburg. (2010) NCI First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biology Underlying Recurrence of Malignant Disease following Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction. Biology of Blood and Marrow Transplantation 16:5, 565-586
CrossRef177
Anneke Van der Walt, Helmut Butzkueven, Scott Kolbe, Mark Marriott, Estella Alexandrou, Melissa Gresle, Gary Egan, Trevor Kilpatrick. (2010) Neuroprotection in multiple sclerosis: A therapeutic challenge for the next decade. Pharmacology & Therapeutics 126:1, 82-93
CrossRef178
S. Y. Lim, C. S. Constantinescu. (2010) Current and future disease-modifying therapies in multiple sclerosis. International Journal of Clinical Practice 64:5, 637-650
CrossRef179
Jerold Chun, Hans-Peter Hartung. (2010) Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis. Clinical Neuropharmacology 33:2, 91-101
CrossRef180
Marie Namey, June Halper, Shirley OʼLeary, Jill Beavin, Cynthia Bishop. (2010) Best Practices in Multiple Sclerosis. Journal of Infusion Nursing 33:2, 98-111
CrossRef181
Sunita Venkateswaran, Brenda Banwell. (2010) Pediatric Multiple Sclerosis. The Neurologist 16:2, 92-105
CrossRef182
Orhan Aktas, Bernd Kieseier, Hans-Peter Hartung. (2010) Neuroprotection, regeneration and immunomodulation: broadening the therapeutic repertoire in multiple sclerosis. Trends in Neurosciences 33:3, 140-152
CrossRef183
Martina A. McAteer, Asim M. Akhtar, Constantin von zur Muhlen, Robin P. Choudhury. (2010) An approach to molecular imaging of atherosclerosis, thrombosis, and vascular inflammation using microparticles of iron oxide. Atherosclerosis 209:1, 18-27
CrossRef184
Lucienne Chatenoud. (2010) Immune therapy for type 1 diabetes mellitus—what is unique about anti-CD3 antibodies?. Nature Reviews Endocrinology 6:3, 149-157
CrossRef185
Joan B. O'Sullivan, Karen M. Ryan, Andrew Harkin, Thomas J. Connor. (2010) Noradrenaline reuptake inhibitors inhibit expression of chemokines IP-10 and RANTES and cell adhesion molecules VCAM-1 and ICAM-1 in the CNS following a systemic inflammatory challenge. Journal of Neuroimmunology 220:1-2, 34-42
CrossRef186
Nancy L Kuntz, Dorothee Chabas, Bianca Weinstock-Guttman, Tanuja Chitnis, E Ann Yeh, Lauren Krupp, Jayne Ness, Moses Rodriguez, Emmanuelle Waubant. (2010) Treatment of multiple sclerosis in children and adolescents. Expert Opinion on Pharmacotherapy 11:4, 505-520
CrossRef187
Samantha Jilek, Emilie Jaquiéry, Hans H Hirsch, Andreas Lysandropoulos, Mathieu Canales, Laurence Guignard, Myriam Schluep, Giuseppe Pantaleo, Renaud A Du Pasquier. (2010) Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study. The Lancet Neurology 9:3, 264-272
CrossRef188
Devon Conway, Jeffrey A Cohen. (2010) Combination therapy in multiple sclerosis. The Lancet Neurology 9:3, 299-308
CrossRef189
Carlo Piccinni, Chiara Sacripanti, Elisabetta Poluzzi, Domenico Motola, Lara Magro, Ugo Moretti, Anita Conforti, Nicola Montanaro. (2010) Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents. European Journal of Clinical Pharmacology 66:2, 199-206
CrossRef190
N Hamerschlak, M Rodrigues, D A Moraes, M C Oliveira, A B P L Stracieri, F Pieroni, G M N Barros, M I A Madeira, B P Simões, A A Barreira, D G Brum, A A F Ribeiro, J M Kutner, C P Tylberi, P P Porto, C L Santana, J Z Neto, J C Barros, A T Paes, R K Burt, E A Oliveira, A P Mastropietro, A C Santos, J C Voltarelli. (2010) Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. Bone Marrow Transplantation 45:2, 239-248
CrossRef191
Olivier Outteryck, J.-C. Ongagna, H. Zéphir, M.-C. Fleury, A. Lacour, F. Blanc, P. Vermersch, J. Sèze. (2010) Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice. Journal of Neurology 257:2, 207-211
CrossRef192
Setsu Sawai, Hiroshi Umemura, Masahiro Mori, Mamoru Satoh, Sei Hayakawa, Yoshio Kodera, Takeshi Tomonaga, Satoshi Kuwabara, Fumio Nomura. (2010) Serum levels of complement C4 fragments correlate with disease activity in multiple sclerosis: Proteomic analysis. Journal of Neuroimmunology 218:1-2, 112-115
CrossRef193
Alan M. Palmer. (2010) The role of the blood–CNS barrier in CNS disorders and their treatment. Neurobiology of Disease 37:1, 3-12
CrossRef194
Masaaki Niino, Hidenao Sasaki. (2010) Update on the treatment options for multiple sclerosis. Expert Review of Clinical Immunology 6:1, 77-88
CrossRef195
Scott M. Steward-Tharp, Yun-jeong Song, Richard M. Siegel, John J. O'Shea. (2010) New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression. Annals of the New York Academy of Sciences 1183:1, 123-148
CrossRef196
Lawrence Steinman. (2010) Mixed results with modulation of TH-17 cells in human autoimmune diseases. Nature Immunology 11:1, 41-44
CrossRef197
Tim Friede, Heinz Schmidli. (2010) Blinded sample size reestimation with count data: Methods and applications in multiple sclerosis. Statistics in Medicinen/a-n/a
CrossRef198
Takeshi OMAE. (2010) Control of Postoperative Atrial Fibrillation. THE JOURNAL OF JAPAN SOCIETY FOR CLINICAL ANESTHESIA 30:5, 771-778
CrossRef199
N. Putzki, O. Yaldizli, M. Mäurer, S. Cursiefen, S. Kuckert, C. Klawe, M. Maschke, B. Tettenborn, V. Limmroth. (2010) Efficacy of natalizumab in second line therapy of relapsingâremitting multiple sclerosis: results from a multi-center study in German speaking countries. European Journal of Neurology 17:1, 31-37
CrossRef200
A. García Merino, O. Fernández, X. Montalbán, C. de Andrés, T. Arbizu. (2010) Spanish Neurology Society consensus document on the use of drugs in multiple sclerosis: Escalating therapy. Neurología (English Edition) 25:6, 378-390
CrossRef201
Gilles Defer, Bruno Brochet, Jean Pelletier. 2010. Principaux traitements. , 21-22.
CrossRef202
Olaf Stüve. (2009) Knowns and unknowns in the future of multiple sclerosis treatment. Journal of the Neurological Sciences 287, S30-S36
CrossRef203
Nathalie Koning, Bernard M.J. Uitdehaag, Inge Huitinga, Robert M. Hoek. (2009) Restoring immune suppression in the multiple sclerosis brain. Progress in Neurobiology 89:4, 359-368
CrossRef204
Patrick J. Brennan, Tito Rodriguez Bouza, F. Ida Hsu, David E. Sloane, Mariana C. Castells. (2009) Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. Journal of Allergy and Clinical Immunology 124:6, 1259-1266
CrossRef205
Maria Pia Sormani. (2009) The Will Rogers phenomenon: the effect of different diagnostic criteria. Journal of the Neurological Sciences 287, S46-S49
CrossRef206
Bettina Schreiner, Frank L. Heppner, Burkhard Becher. (2009) Modeling multiple sclerosis in laboratory animals. Seminars in Immunopathology 31:4, 479-495
CrossRef207
Jerry S. Wolinsky, Tzippy Shochat, Sivan Weiss, David Ladkani. (2009) Glatiramer acetate treatment in PPMS: Why males appear to respond favorably. Journal of the Neurological Sciences 286:1-2, 92-98
CrossRef208
Richard Daneman, Maria Rescigno. (2009) The Gut Immune Barrier and the Blood-Brain Barrier: Are They So Different?. Immunity 31:5, 722-735
CrossRef209
Brady Huggett. (2009) How Tysabri survived. Nature Biotechnology 27:11, 986-986
CrossRef210
John H Pula, Adil Javed. (2009) Multiple sclerosis. Part 2: Ophthalmic issues in MS therapy. Current Opinion in Ophthalmology 20:6, 476-481
CrossRef211
Eva de Lago, María Gómez-Ruiz, Miguel Moreno-Martet, Javier Fernández-Ruiz. (2009) Cannabinoids, multiple sclerosis and neuroprotection. Expert Review of Clinical Pharmacology 2:6, 645-660
CrossRef212
H.-P. Hartung, C. Warnke, R. Hohlfeld, B.C. Kieseier. (2009) Progressive multifokale Leukenzephalopathie. Der Nervenarzt 80:10, 1143-1153
CrossRef213
Simon Eckermann, Michael Coory, Andrew R. Willan. (2009) Indirect comparison: relative risk fallacies and odds solution. Journal of Clinical Epidemiology 62:10, 1031-1036
CrossRef214
Giancarlo Comi. (2009) Treatment of multiple sclerosis: role of natalizumab. Neurological Sciences 30:S2, 155-158
CrossRef215
G. Tedeschi, M. P. Amato, R. D’Alessandro, F. Drago, C. Milanese, P. Popoli, P. Rossi, G. Savettieri, M. R. Tola, N. Vanacore, A. Covezzoli, M. Rosa, G. Comi, Carlo Pozzilli, Antonio Bertolotto, Maria Giovanna Marrosu, Luigi M. E. Grimaldi, C. Piccinni, N. Montanaro, Laura Periotto, Rosamaria Iommelli, Antonio Addis, Nello Martini, L. Provinciali, G. L. Mancardi. (2009) The pharmacovigilance program on natalizumab in Italy: 2 years of experience. Neurological Sciences 30:S2, 163-165
CrossRef216
Roopa Bhat, Lawrence Steinman. (2009) Innate and Adaptive Autoimmunity Directed to the Central Nervous System. Neuron 64:1, 123-132
CrossRef217
Stephen L. Nishimura. (2009) Integrin-Mediated Transforming Growth Factor-β Activation, a Potential Therapeutic Target in Fibrogenic Disorders. The American Journal of Pathology 175:4, 1362-1370
CrossRef218
Jordi Río, Manuel Comabella, Xavier Montalban. (2009) Predicting responders to therapies for multiple sclerosis. Nature Reviews Neurology 5:10, 553-560
CrossRef219
Azza Ismail, Julie Kemp, Basil Sharrack. (2009) Melanoma complicating treatment with Natalizumab (Tysabri) for multiple sclerosis. Journal of Neurology 256:10, 1771-1772
CrossRef220
P. Iaffaldano, M. D’Onghia, Maria Trojano. (2009) Safety profile of Tysabri: international risk management plan. Neurological Sciences 30:S2, 159-162
CrossRef221
Norman Putzki, Özgür Yaldizli, Barbara Tettenborn, Hans Christoph Diener. (2009) Multiple sclerosis associated fatigue during natalizumab treatment. Journal of the Neurological Sciences 285:1-2, 109-113
CrossRef222
Stephen M Anderton. 2009. Immunological Tolerance: Therapeutic Induction. .
CrossRef223
Lindå, Hans, von Heijne, Anders, Major, Eugene O., Ryschkewitsch, Caroline, Berg, Johan, Olsson, Tomas, Martin, Claes, . (2009) Progressive Multifocal Leukoencephalopathy after Natalizumab Monotherapy. New England Journal of Medicine 361:11, 1081-1087
Full Text224
Hideki Garren. (2009) DNA vaccines for autoimmune diseases. Expert Review of Vaccines 8:9, 1195-1203
CrossRef225
Moutih Rafei, Jeremy Hsieh, Simone Zehntner, MengYang Li, Kathy Forner, Elena Birman, Marie-Noëlle Boivin, Yoon Kow Young, Claude Perreault, Jacques Galipeau. (2009) A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nature Medicine 15:9, 1038-1045
CrossRef226
Norbert Goebels, Ludwig Kappos. (2009) Another complication of natalizumab treatment? Taking the challenge. Annals of Neurology 66:3, 264-266
CrossRef227
Carmen Bozic, Julia LaGuette, Michael A. Panzara, Alfred W. Sandrock. (2009) Natalizumab and central nervous system lymphoma: No clear association. Annals of Neurology 66:3, 261-262
CrossRef228
Jasmina I. Ivanova, Howard G. Birnbaum, Seth Samuels, Matthew Davis, Amy L. Phillips, Dennis Meletiche. (2009) The Cost of Disability and Medically Related Absenteeism Among Employees with Multiple Sclerosis in the US. PharmacoEconomics 27:8, 681-691
CrossRef229
Aran F Labrijn, Antonio Ortiz Buijsse, Ewald T J van den Bremer, Annemiek Y W Verwilligen, Wim K Bleeker, Susan J Thorpe, Joep Killestein, Chris H Polman, Rob C Aalberse, Janine Schuurman, Jan G J van de Winkel, Paul W H I Parren. (2009) Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nature Biotechnology 27:8, 767-771
CrossRef230
Manuel A. Friese, Lars Fugger. (2009) Pathogenic CD8 + T cells in multiple sclerosis. Annals of Neurology 66:2, 132-141
CrossRef231
Kenneth R Carson, Daniele Focosi, Eugene O Major, Mario Petrini, Elizabeth A Richey, Dennis P West, Charles L Bennett. (2009) Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. The Lancet Oncology 10:8, 816-824
CrossRef232
Holger Nückel, Magdalena Switala, Crista H. Collins, Ludger Sellmann, Hans Grosse-Wilde, Ulrich Dührsen, Vera Rebmann. (2009) High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia. Clinical Immunology 131:3, 472-480
CrossRef233
Richard A Rudick, Chris H Polman. (2009) Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. The Lancet Neurology 8:6, 545-559
CrossRef234
Siddhesh A. Kamat, Krithika Rajagopalan, Judith J. Stephenson, Sonalee Agarwal. (2009) Impact of Natalizumab on Patient-Reported Outcomes in a Clinical Practice Setting. The Patient: Patient-Centered Outcomes Research 2:2, 105-112
CrossRef235
Per Soelberg Sorensen, Svein Ivar Mellgren, Anders Svenningsson, Irina Elovaara, Jette Lautrup Frederiksen, Antonie Giaever Beiske, Kjell-Morten Myhr, Lise Vejby Søgaard, Inge Christoffer Olsen, Magnhild Sandberg-Wollheim. (2009) NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial. The Lancet Neurology 8:6, 519-529
CrossRef236
Marco Salvetti, Gavin Giovannoni, Francesca Aloisi. (2009) Epstein–Barr virus and multiple sclerosis. Current Opinion in Neurology 22:3, 201-206
CrossRef237
Nancy G. Wehner, Carolyn Gasper, George Shopp, Joyce Nelson, Ken Draper, Suezanne Parker, Janet Clarke. (2009) Immunotoxicity profile of natalizumab. Journal of Immunotoxicology 6:2, 115-129
CrossRef238
Lawrence Steinman. (2009) A molecular trio in relapse and remission in multiple sclerosis. Nature Reviews Immunology 9:6, 440-447
CrossRef239
Lars Fugger, Manuel A. Friese, John I. Bell. (2009) From genes to function: the next challenge to understanding multiple sclerosis. Nature Reviews Immunology 9:6, 408-417
CrossRef240
Evelyn Chiao, Kellie Meyer. (2009) Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis. Current Medical Research and Opinion 25:6, 1445-1454
CrossRef241
Sophie G. Fletcher, Gary E. Lemack. (2009) Evaluation and management of neurogenic vesicourethral dysfunction in multiple sclerosis. Current Bladder Dysfunction Reports 4:2, 71-78
CrossRef242
Florian Deisenhammer. (2009) Neutralizing Antibodies to Interferon-β and other Immunological Treatments for Multiple Sclerosis. CNS Drugs 23:5, 379-396
CrossRef243
Jeffrey L. Bennett, Olaf Stüve. (2009) Update on Inflammation, Neurodegeneration, and Immunoregulation in Multiple Sclerosis. Clinical Neuropharmacology 32:3, 121-132
CrossRef244
Krupa Pandey, Fred D. Lublin. (2009) Clinically isolated syndrome and multiple sclerosis: Rethinking the arsenal. Current Treatment Options in Neurology 11:3, 193-202
CrossRef245
Ö. Yaldizli, P. Baumberger, N. Putzki. (2009) Natalizumab et nævus atypiques : commentaires sur la note de pharmacovigilance de J.-L. Schmutz et al.. Annales de Dermatologie et de Vénéréologie 136:5, 450-451
CrossRef246
John W. Rose, John F. Foley, Noel G. Carlson. (2009) Monoclonal antibody treatments for multiple sclerosis. Current Treatment Options in Neurology 11:3, 211-220
CrossRef247
J Ludovic Croxford, Takashi Yamamura. (2009) Back to the future for multiple sclerosis therapy: focus on current and emerging disease-modifying therapeutic strategies. Immunotherapy 1:3, 403-423
CrossRef248
Shumei Man, Barbara Tucky, Nika Bagheri, Xiaolong Li, Rabina Kochar, Richard M. Ransohoff. (2009) α4 Integrin/FN-CS1 mediated leukocyte adhesion to brain microvascular endothelial cells under flow conditions. Journal of Neuroimmunology 210:1-2, 92-99
CrossRef249
F. Reed Johnson, George Houtven, Semra Özdemir, Steve Hass, Jeff White, Gordon Francis, David W. Miller, J. Theodore Phillips. (2009) Multiple sclerosis patients—benefit-risk preferences: Serious adverse event risks versus treatment efficacy. Journal of Neurology 256:4, 554-562
CrossRef250
Howard G. Birnbaum, Jasmina I. Ivanova, Seth Samuels, Matthew Davis, Pierre Y. Cremieux, Amy L. Phillips, Dennis Meletiche. (2009) Economic impact of multiple sclerosis disease-modifying drugs in an employed population: direct and indirect costs*. Current Medical Research and Opinion 25:4, 869-877
CrossRef251
M. Khademi, L. Bornsen, F. Rafatnia, M. Andersson, L. Brundin, F. Piehl, F. Sellebjerg, T. Olsson. (2009) The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers. European Journal of Neurology 16:4, 528-536
CrossRef252
Joseph R. Berger, Sidney Houff. (2009) Opportunistic infections and other risks with newer multiple sclerosis therapies. Annals of Neurology 65:4, 367-377
CrossRef253
Nancy G. Wehner, Michael Skov, George Shopp, Meredith S. Rocca, Janet Clarke. (2009) Effects of natalizumab, an α4 integrin inhibitor, on fertility in male and female guinea pigs. Birth Defects Research Part B: Developmental and Reproductive Toxicology 86:2, 108-116
CrossRef254
Nicolas Weiss, Florence Miller, Sylvie Cazaubon, Pierre-Olivier Couraud. (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochimica et Biophysica Acta (BBA) - Biomembranes 1788:4, 842-857
CrossRef255
P. L. De Jager, C. Baecher-Allan, L. M. Maier, A. T. Arthur, L. Ottoboni, L. Barcellos, J. L. McCauley, S. Sawcer, A. Goris, J. Saarela, R. Yelensky, A. Price, V. Leppa, N. Patterson, P. I. W. de Bakker, D. Tran, C. Aubin, S. Pobywajlo, E. Rossin, X. Hu, C. W. Ashley, E. Choy, J. D. Rioux, M. A. Pericak-Vance, A. Ivinson, D. R. Booth, G. J. Stewart, A. Palotie, L. Peltonen, B. Dubois, J. L. Haines, H. L. Weiner, A. Compston, S. L. Hauser, M. J. Daly, D. Reich, J. R. Oksenberg, D. A. Hafler. (2009) The role of the CD58 locus in multiple sclerosis. Proceedings of the National Academy of Sciences 106:13, 5264-5269
CrossRef256
Joachim R Kalden, Harald Burkhardt. 2009. Autoimmune Disease: Treatment. .
CrossRef257
Maria Pia Sormani, Laura Bonzano, Luca Roccatagliata, Gary R. Cutter, Gian Luigi Mancardi, Paolo Bruzzi. (2009) Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: A meta-analytic approach. Annals of Neurology 65:3, 268-275
CrossRef258
N. Putzki, K. Kollia, S. Woods, E. Igwe, H. C. Diener, V. Limmroth. (2009) Natalizumab is effective as second line therapy in the treatment of relapsing remitting multiple sclerosis. European Journal of Neurology 16:3, 424-426
CrossRef259
P. S. Sorensen. (2009) How effective is natalizumab as second-line treatment for multiple sclerosis in daily clinical praxis?. European Journal of Neurology 16:3, 287-288
CrossRef260
Patricia K Coyle. (2009) Existing therapies for multiple sclerosis offer proven efficacy and safety. Current Opinion in Neurology 22:Suppl 1, S4-S9
CrossRef261
A. B. Oturai, N. Koch-Henriksen, T. Petersen, P. E. H. Jensen, F. Sellebjerg, P. S. Sorensen. (2009) Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study. European Journal of Neurology 16:3, 420-423
CrossRef262
Wenjun Ouyang, Ellen Filvaroff, Yan Hu, Jane Grogan. (2009) Novel therapeutic targets along the Th17 pathway. European Journal of Immunology 39:3, 670-675
CrossRef263
, M. Hutchinson, L. Kappos, P. A. Calabresi, C. Confavreux, G. Giovannoni, S. L. Galetta, E. Havrdova, F. D. Lublin, D. H. Miller, P. W. O’Connor, J. T. Phillips, C. H. Polman, E.-W. Radue, R. A. Rudick, W. H. Stuart, A. Wajgt, B. Weinstock-Guttman, D. R. Wynn, F. Lynn, M. A. Panzara. (2009) The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. Journal of Neurology 256:3, 405-415
CrossRef264
Carlo Pozzilli, Nikolaos Petsas, Luca Prosperini. (2009) MRI for monitoring response to preventive treatment in multiple sclerosis. Expert Review of Neurotherapeutics 9:3, 305-307
CrossRef265
Laurie J. Barten, Douglas R. Allington, Kendra A. Procacci, Michael P. Rivey. (2009) Natalizumab update: a story of benefit and risk. Drug Discovery Today: Therapeutic Strategies 6:1, 21-31
CrossRef266
N. García-Barragán, L. M. Villar, M. Espiño, M. C. Sádaba, P. González-Porqué, J. C. Álvarez-Cermeño. (2009) Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment. European Journal of Neurology 16:3, 380-385
CrossRef267
M. Bauer, C. Brakebusch, C. Coisne, M. Sixt, H. Wekerle, B. Engelhardt, R. Fassler. (2009) 1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity. Proceedings of the National Academy of Sciences 106:6, 1920-1925
CrossRef268
M. Kerschensteiner, E. Meinl, R. Hohlfeld. (2009) Neuro-immune crosstalk in CNS diseases. Neuroscience 158:3, 1122-1132
CrossRef269
Jeffrey A. Cohen. (2009) The future of multiple sclerosis treatment. Journal of the Neurological Sciences 277, S55-S61
CrossRef270
Paul M. Matthews. (2009) Brain Imaging of Multiple Sclerosis: the Next 10 Years. Neuroimaging Clinics of North America 19:1, 101-112
CrossRef271
Anat Achiron, Sten Fredrikson. (2009) Lessons from randomised direct comparative trials. Journal of the Neurological Sciences 277, S19-S24
CrossRef272
Sylvia E Kim. (2009) Daclizumab Treatment for Multiple Sclerosis. Pharmacotherapy 29:2, 227-235
CrossRef273
L. Mestre, F. Docagne, F. Correa, F. Loría, M. Hernangómez, J. Borrell, C. Guaza. (2009) A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules. Molecular and Cellular Neuroscience 40:2, 258-266
CrossRef274
Peter Rieckmann. (2009) Concepts of induction and escalation therapy in multiple sclerosis. Journal of the Neurological Sciences 277, S42-S45
CrossRef275
M. Kleinewietfeld, M. Starke, D. Di Mitri, G. Borsellino, L. Battistini, O. Rotzschke, K. Falk. (2009) CD49d provides access to "untouched" human Foxp3+ Treg free of contaminating effector cells. Blood 113:4, 827-836
CrossRef276
Eugenio Pucci, Giorgio Giuliani, Alessandra Solari, Carlo Di Pietrantonj, Silvana Simi, Silvia Minozzi, Ian Galea, Eugenio Pucci. 2009. Natalizumab for relapsing remitting multiple sclerosis. .
CrossRef277
Giovanna Borriello, Luca Prosperini, Anna Luchetti, Carlo Pozzilli. (2009) Natalizumab treatment in pediatric multiple sclerosis: A case report. European Journal of Paediatric Neurology 13:1, 67-71
CrossRef278
A. Solari. (2009) Participatory decision making in multiple sclerosis. European Journal of Neurology 16:1, 3-4
CrossRef279
Heather J MacLean, Mark S Freedman. (2009) Multiple sclerosis: following clues from cause to cure. The Lancet Neurology 8:1, 6-8
CrossRef280
David W. Brandes, Teri Callender, Ellen Lathi, Shirley O’Leary. (2009) A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events. Current Medical Research and Opinion 25:1, 77-92
CrossRef281
Bruce A. Cohen, Joel Oger, Alison Gagnon, Gavin Giovannoni. (2008) The implications of immunogenicity for protein-based multiple sclerosis therapies. Journal of the Neurological Sciences 275:1-2, 7-17
CrossRef282
Georg Pilz, Peter Wipfler, Gunther Ladurner, Jörg Kraus. (2008) Modern multiple sclerosis treatment – what is approved, what is on the horizon. Drug Discovery Today 13:23-24, 1013-1025
CrossRef283
Olaf Stüve, Ralf Gold, Andrew Chan, Eilhard Mix, Uwe Zettl, Bernd C. Kieseier. (2008) α4-Integrin antagonism with natalizumab. Journal of Neurology 255:S6, 58-65
CrossRef284
P. S. Rommer, O. Stüve, R. Goertsches, E. Mix, U. K. Zettl. (2008) Monoclonal antibodies in the therapy of multiple sclerosis. Journal of Neurology 255:S6, 28-35
CrossRef285
John J Bright, Crystal C Walline, Sarvanan Kanakasabai, Sharmistha Chakraborty. (2008) Targeting PPAR as a therapy to treat multiple sclerosis. Expert Opinion on Therapeutic Targets 12:12, 1565-1575
CrossRef286
Paolo F Fabene, Graciela Navarro Mora, Marianna Martinello, Barbara Rossi, Flavia Merigo, Linda Ottoboni, Simona Bach, Stefano Angiari, Donatella Benati, Asmaa Chakir, Lara Zanetti, Federica Schio, Antonio Osculati, Pasquina Marzola, Elena Nicolato, Jonathon W Homeister, Lijun Xia, John B Lowe, Rodger P McEver, Francesco Osculati, Andrea Sbarbati, Eugene C Butcher, Gabriela Constantin. (2008) A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nature Medicine 14:12, 1377-1383
CrossRef287
Britta Engelhardt. (2008) Immune cell entry into the central nervous system: Involvement of adhesion molecules and chemokines. Journal of the Neurological Sciences 274:1-2, 23-26
CrossRef288
Rocio S. Lopez-Diego, Howard L. Weiner. (2008) Novel therapeutic strategies for multiple sclerosis — a multifaceted adversary. Nature Reviews Drug Discovery 7:11, 909-925
CrossRef289
Mar Tintoré, Jaume Sastre-Garriga. (2008) New treatment measurements for treatment effects on relapses and progression. Journal of the Neurological Sciences 274:1-2, 80-83
CrossRef290
Christian K. Schneider, Gabriele Schäffner-Dallmann. (2008) Typical pitfalls in applications for marketing authorization of biotechnological products in Europe. Nature Reviews Drug Discovery 7:11, 893-899
CrossRef291
Douglas R Jeffery. (2008) Development of laquinimod for relapsing–remitting multiple sclerosis. Future Neurology 3:6, 641-648
CrossRef292
Robert A. Bermel, Elizabeth Fisher, Jeffrey A. Cohen. (2008) The Use of MR Imaging as an Outcome Measure in Multiple Sclerosis Clinical Trials. Neuroimaging Clinics of North America 18:4, 687-701
CrossRef293
Manuel A Friese, Karen B Jakobsen, Lone Friis, Ruth Etzensperger, Matthew J Craner, Róisín M McMahon, Lise T Jensen, Véronique Huygelen, E Yvonne Jones, John I Bell, Lars Fugger. (2008) Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nature Medicine 14:11, 1227-1235
CrossRef294
B.K. Kleinschmidt-DeMasters, Denise M. Damek, Kevin O. Lillehei, Ahmed Dogan, Caterina Giannini. (2008) Epstein Barr Virus-Associated Primary CNS Lymphomas in Elderly Patients on Immunosuppressive Medications. Journal of Neuropathology and Experimental Neurology 67:11, 1103-1111
CrossRef295
Marinella Clerico, Chiara Rivoiro, Giulia Contessa, Daniela Viglietti, Luca Durelli. (2008) The therapy of multiple sclerosis with immune-modulating or immunosuppressive drug. Clinical Neurology and Neurosurgery 110:9, 878-885
CrossRef296
Richard J. Davenport, James R. Munday. (2008) Blocking α4-integrins — A small molecule approach to treatment of multiple sclerosis. Journal of the Neurological Sciences 274:1-2, 27-30
CrossRef297
Ralf A. Linker, Bernd C. Kieseier, Ralf Gold. (2008) Identification and development of new therapeutics for multiple sclerosis. Trends in Pharmacological Sciences 29:11, 558-565
CrossRef298
Elliot M. Frohman, Todd Eagar, Nancy Monson, Olaf Stuve, Nitin Karandikar. (2008) Immunologic Mechanisms of Multiple Sclerosis. Neuroimaging Clinics of North America 18:4, 577-588
CrossRef299
Alastair Compston, Alasdair Coles. (2008) Multiple sclerosis. The Lancet 372:9648, 1502-1517
CrossRef300
Richard A Rudick, Sha Mi, Alfred W Sandrock. (2008) LINGO-1 antagonists as therapy for multiple sclerosis: in vitro and in vivo evidence. Expert Opinion on Biological Therapy 8:10, 1561-1570
CrossRef301
Jessica R Philpott, Philip B Miner. (2008) Antisense inhibition of ICAM-1 expression as therapy provides insight into basic inflammatory pathways through early experiences in IBD. Expert Opinion on Biological Therapy 8:10, 1627-1632
CrossRef302
Daniel D Mikol, Frederik Barkhof, Peter Chang, Patricia K Coyle, Douglas R Jeffery, Steven R Schwid, Bettina Stubinski, Bernard MJ Uitdehaag. (2008) Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. The Lancet Neurology 7:10, 903-914
CrossRef303
R.A. Linker, B.C. Kieseier. (2008) Therapieentscheidungen bei Multipler Sklerose. Der Nervenarzt 79:10, 1123-1134
CrossRef304
Maria Pia Sormani, Mar Tintorè, Marco Rovaris, Alex Rovira, Xavier Vidal, Paolo Bruzzi, Massimo Filippi, Xavier Montalban. (2008) Will Rogers phenomenon in multiple sclerosis. Annals of Neurology 64:4, 428-433
CrossRef305
J.-L. Schmutz, A. Barbaud, P. Tréchot. (2008) Mélanome et traitement de la sclérose en plaques par natalizumab (Tysabri®). Annales de Dermatologie et de Vénéréologie 135:10, 725-726
CrossRef306
, H. Wiendl, K. V. Toyka, P. Rieckmann, R. Gold, H.-P. Hartung, R. Hohlfeld. (2008) Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. Journal of Neurology 255:10, 1449-1463
CrossRef307
Bianca Weinstock-Guttman, Murali Ramanathan, Robert Zivadinov. (2008) Interferon-β treatment for relapsing multiple sclerosis. Expert Opinion on Biological Therapy 8:9, 1435-1447
CrossRef308
Gian Luigi Mancardi, Maria Pia Amato, Roberto D’Alessandro, Filippo Drago, Clara Milanese, Patrizia Popoli, Leandro Provinciali, Pasqualino Rossi, Giovanni Savettieri, Gioacchino Tedeschi, Maria Rosaria Tola, Nicola Vanacore, Anna Covezzoli, Marisa Rosa, Carlo Piccinni, Nicola Montanaro, Laura Periotto, Antonio Addis, Nello Martini. (2008) Natalizumab: a country-based surveillance program. Neurological Sciences 29:S2, 235-237
CrossRef309
C. Infante-Duarte, S. Waiczies, J. Wuerfel, F. Zipp. (2008) New developments in understanding and treating neuroinflammation. Journal of Molecular Medicine 86:9, 975-985
CrossRef310
John W. Rose, John Foley, Noel Carlson. (2008) Monoclonal antibody treatments for multiple sclerosis. Current Neurology and Neuroscience Reports 8:5, 419-426
CrossRef311
Mark S. Freedman. (2008) Induction vs. escalation of therapy for relapsing Multiple Sclerosis: the evidence. Neurological Sciences 29:S2, 250-252
CrossRef312
Manuel Comabella. (2008) Pharmacogenomics in multiple sclerosis: getting the right medicine to the right patient. Therapy 5:5, 623-629
CrossRef313
Diego Franciotta, Marco Salvetti, Francesco Lolli, Barbara Serafini, Francesca Aloisi. (2008) B cells and multiple sclerosis. The Lancet Neurology 7:9, 852-858
CrossRef314
Charles R Mackay. (2008) Moving targets: cell migration inhibitors as new anti-inflammatory therapies. Nature Immunology 9:9, 988-998
CrossRef315
Richard A Rudick. (2008) Multiple sclerosis therapeutics: opportunities, strategies and challenges. Therapy 5:5, 585-587
CrossRef316
Dennis Bourdette, Vijayshree Yadav. (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. Current Neurology and Neuroscience Reports 8:5, 417-418
CrossRef317
Michael K Racke, Amy E Lovett-Racke. (2008) What are new therapies teaching us about the immunology of multiple sclerosis?. Therapy 5:5, 589-591
CrossRef318
Harold Moses, David W. Brandes. (2008) Managing adverse effects of disease-modifying agents used for treatment of multiple sclerosis. Current Medical Research and Opinion 24:9, 2679-2690
CrossRef319
V. I. Leussink, H. C. Lehmann, G. Meyer zu Hörste, H.-P. Hartung, O. Stüve, B. C. Kieseier. (2008) Rituximab induces clinical stabilization in a patient with fulminant multiple sclerosis not responding to natalizumab. Journal of Neurology 255:9, 1436-1438
CrossRef320
Claudio Gasperini, Luca Ausili Cefaro, Giovanna Borriello, Giuseppe Tosto, Luca Prosperini, Carlo Pozzilli. (2008) Emerging oral drugs for multiple sclerosis. Expert Opinion on Emerging Drugs 13:3, 465-477
CrossRef321
M.V. Jones, T.T. Nguyen, C.A. DeBoy, J.W. Griffin, K.A. Whartenby, D.A. Kerr, P.A. Calabresi. (2008) Behavioral and pathological outcomes in MOG 35–55 experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 199:1-2, 83-93
CrossRef322
Francisco J. Quintana, Mauricio F. Farez, Howard L. Weiner. (2008) Translational Therapies for Immune-based Disorders Review Series: Systems biology approaches for the study of multiple sclerosis. Journal of Cellular and Molecular Medicine 12:4, 1087-1093
CrossRef323
Jefferson W Tilley. (2008) Very late antigen-4 integrin antagonists. Expert Opinion on Therapeutic Patents 18:8, 841-859
CrossRef324
(2008) More on Melanoma with Transdifferentiation. New England Journal of Medicine 359:1, 99-100
Full Text325
C. Ytterberg, S. Johansson, M. Andersson, L. Widén Holmqvist, L. Koch. (2008) Variations in functioning and disability in multiple sclerosis. Journal of Neurology 255:7, 967-973
CrossRef326
Gianluigi Mancardi, Riccardo Saccardi. (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. The Lancet Neurology 7:7, 626-636
CrossRef327
Maria Katsara, John Matsoukas, George Deraos, Vasso Apostolopoulos. (2008) Towards immunotherapeutic drugs and vaccines against multiple sclerosis. Acta Biochimica et Biophysica Sinica 40:7, 636-642
CrossRef328
Shane M Devlin, Remo Panaccione. (2008) Adalimumab for the treatment of Crohn's disease. Expert Opinion on Biological Therapy 8:7, 1011-1019
CrossRef329
Bart Van Wijmeersch, Ben Sprangers, Bénédicte Dubois, Mark Waer, An D. Billiau. (2008) Autologous and allogeneic hematopoietic stem cell transplantation for Multiple Sclerosis: Perspective on mechanisms of action. Journal of Neuroimmunology 197:2, 89-98
CrossRef330
Bruce D. Trapp, Klaus-Armin Nave. (2008) Multiple Sclerosis: An Immune or Neurodegenerative Disorder?. Annual Review of Neuroscience 31:1, 247-269
CrossRef331
David B. Sommer, Larry B. Goldstein. 2008. Central Nervous System (CNS). .
CrossRef332
Pietro Bulian, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei. (2008) CD49d expression in chronic lymphocytic leukemia: a prognostic parameter and a therapeutic target. Future Oncology 4:3, 355-358
CrossRef333
G Comi, A Pulizzi, M Rovaris, O Abramsky, T Arbizu, A Boiko, R Gold, E Havrdova, S Komoly, KW Selmaj, B Sharrack, M Filippi. (2008) Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. The Lancet 371:9630, 2085-2092
CrossRef334
A. Haghikia, M. Fischer, K. Hellwig, R. Linker, A. Chan, R. Hohlfeld, R. Gold. (2008) Natalizumab im klinischen Alltag. Der Nervenarzt 79:6, 716-719
CrossRef335
Phillip G. Popovich, Erin E. Longbrake. (2008) Can the immune system be harnessed to repair the CNS?. Nature Reviews Neuroscience 9:6, 481-493
CrossRef336
Tracy DeAngelis, Fred Lublin. (2008) Multiple sclerosis: new treatment trials and emerging therapeutic targets. Current Opinion in Neurology 21:3, 261-271
CrossRef337
Isobel A. Scarisbrick, Rachel Linbo, Alexander G. Vandell, Mark Keegan, Sachiko I. Blaber, Michael Blaber, Diane Sneve, Claudia F. Lucchinetti, Moses Rodriguez, Eleftherios P. Diamandis. (2008) Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration. Biological Chemistry 389:6, 739-745
CrossRef338
B. Olsson, B. Ridell, L. Carlsson, S. Jacobsson, H. Wadenvik. (2008) Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1. Blood 112:4, 1078-1084
CrossRef339
Hideki Garren, William H. Robinson, Eva Krasulová, Eva Havrdová, Congor Nadj, Krzysztof Selmaj, Jacek Losy, Ilinka Nadj, Ernst-Wilhelm Radue, Brian A. Kidd, Jill Gianettoni, Karen Tersini, Paul J. Utz, Frank Valone, Lawrence Steinman, . (2008) Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Annals of Neurology 63:5, 611-620
CrossRef340
Kjell-Morten Myhr. (2008) Diagnosis and treatment of multiple sclerosis. Acta Neurologica Scandinavica 117:s188, 12-21
CrossRef341
Alejandro Horga, Xavier Montalban. (2008) FTY720 (fingolimod) for relapsing multiple sclerosis. Expert Review of Neurotherapeutics 8:5, 699-714
CrossRef342
Raoul D Oude Engberink, Erwin L A Blezer, Erik I Hoff, Susanne M A van der Pol, Annette van der Toorn, Rick M Dijkhuizen, Helga E de Vries. (2008) MRI of monocyte infiltration in an animal model of neuroinflammation using SPIO-labeled monocytes or free USPIO. Journal of Cerebral Blood Flow & Metabolism 28:4, 841-851
CrossRef343
Karen Honey. (2008) The comeback kid: TYSABRI now FDA approved for Crohn disease. Journal of Clinical Investigation 118:3, 825-826
CrossRef344
Tracy DeAngelis, Fred Lublin. (2008) Neurotherapeutics in multiple sclerosis: Novel agents and emerging treatment strategies. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 75:2, 157-167
CrossRef345
Mathias Buttmann, Peter Rieckmann. (2008) Treating multiple sclerosis with monoclonal antibodies. Expert Review of Neurotherapeutics 8:3, 433-455
CrossRef346
Tait D. Shanafelt, Susan M. Geyer, Nancy D. Bone, Renee C. Tschumper, Tom E. Witzig, Greg S. Nowakowski, Clive S. Zent, Tim G. Call, Betsy LaPlant, Gordon W. Dewald, Diane F. Jelinek, Neil E. Kay. (2008) CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. British Journal of Haematology 140:5, 537-546
CrossRef347
Ralf Gold. (2008) Combination therapies in multiple sclerosis. Journal of Neurology 255:S1, 51-60
CrossRef348
M. Khademi, D. Stol, T. Olsson, E. Wallström. (2008) Induction of systemic TNFα in Natalizumab-treated multiple sclerosis. European Journal of Neurology 15:3, 309-312
CrossRef349
Silva Markovic-Plese, Avtar K Singh, Inderjit Singh. (2008) Therapeutic potential of statins in multiple sclerosis: immune modulation, neuroprotection and neurorepair. Future Neurology 3:2, 153-167
CrossRef350
Linda L. Chang, Ginger X. Yang, Ermengilda McCauley, Richard A. Mumford, John A. Schmidt, William K. Hagmann. (2008) Constraining the amide bond in N-Sulfonylated dipeptide VLA-4 antagonists. Bioorganic & Medicinal Chemistry Letters 18:5, 1688-1691
CrossRef351
Hauser, Stephen L., Waubant, Emmanuelle, Arnold, Douglas L., Vollmer, Timothy, Antel, Jack, Fox, Robert J., Bar-Or, Amit, Panzara, Michael, Sarkar, Neena, Agarwal, Sunil, Langer-Gould, Annette, Smith, Craig H., . (2008) B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis. New England Journal of Medicine 358:7, 676-688
Full Text352
Mullen, John T., Vartanian, Timothy K., Atkins, Michael B., . (2008) Melanoma Complicating Treatment with Natalizumab for Multiple Sclerosis. New England Journal of Medicine 358:6, 647-648
Full Text353
Raija L.P. Lindberg, Lutz Achtnichts, Francine Hoffmann, Jens Kuhle, Ludwig Kappos. (2008) Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. Journal of Neuroimmunology 194:1-2, 153-164
CrossRef354
Trygve Holmoy, Elisabeth Gulowsen Celius. (2008) Cost–effectiveness of natalizumab in multiple sclerosis. Expert Review of Pharmacoeconomics & Outcomes Research 8:1, 11-21
CrossRef355
Aaron Boster, Gilles Edan, Elliott Frohman, Adil Javed, Olaf Stuve, Alexandros Tselis, Howard Weiner, Bianca Weinstock-Guttman, Omar Khan. (2008) Intense immunosuppression in patients with rapidly worsening multiple sclerosis: treatment guidelines for the clinician. The Lancet Neurology 7:2, 173-183
CrossRef356
C. L. Hirst, A. Pace, T. P. Pickersgill, R. Jones, B. N. McLean, J. P. Zajicek, N. J. Scolding, N. P. Robertson. (2008) Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis. Journal of Neurology 255:2, 231-238
CrossRef357
Robert M. Friedman. (2008) Clinical uses of interferons. British Journal of Clinical Pharmacology 65:2, 158-162
CrossRef358
J. Ludovic Croxford, Gareth Pryce, Samuel J. Jackson, Catherine Ledent, Gavin Giovannoni, Roger G. Pertwee, Takashi Yamamura, David Baker. (2008) Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. Journal of Neuroimmunology 193:1-2, 120-129
CrossRef359
Edward Neuwelt, N Joan Abbott, Lauren Abrey, William A Banks, Brian Blakley, Thomas Davis, Britta Engelhardt, Paula Grammas, Maiken Nedergaard, John Nutt, William Pardridge, Gary A Rosenberg, Quentin Smith, Lester R Drewes. (2008) Strategies to advance translational research into brain barriers. The Lancet Neurology 7:1, 84-96
CrossRef360
Richard A Rudick, Deborah M Miller. (2008) Health-Related Quality of Life in Multiple Sclerosis. CNS Drugs 22:10, 827-839
CrossRef361
Til Menge, Martin S Weber, Bernhard Hemmer, Bernd C Kieseier, Hans-Christian von Büdingen, Clemens Warnke, Scott S Zamvil, Aaron Boster, Omar Khan, Hans-Peter Hartung, Olaf Stüve. (2008) Disease-Modifying Agents for Multiple Sclerosis. Drugs 68:17, 2445-2468
CrossRef362
Arthur A Vandenbark, Rivka Abulafia-Lapid. (2008) Autologous T-Cell Vaccination for Multiple Sclerosis. BioDrugs 22:4, 265-273
CrossRef363
Susan J. Lee, Arthur F. Kavanaugh. 2008. Monoclonal antibodies and fusion proteins. , 1405-1416.
CrossRef364
K. Ohkuma, T. Sasaki, S. Kamei, S. Okuda, H. Nakano, T. Hamamoto, K. Fujihara, I. Nakashima, T. Misu, Y. Itoyama. (2007) Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients. Clinical & Experimental Immunology 150:3, 397-406
CrossRef365
Paolo Campi, Maurizio Benucci, Mariangela Manfredi, Pascal Demoly. (2007) Hypersensitivity reactions to biological agents with special emphasis on tumor necrosis factor-?? antagonists. Current Opinion in Internal Medicine 6:6, 551-561
CrossRef366
R. Gold, P. Rieckmann. (2007) Fortschritte im Verständnis von Pathogenese und Immuntherapie der Multiplen Sklerose. Der Nervenarzt 78:S1, 15-26
CrossRef367
C. Kleinschnitz, S. G. Meuth, O. Stüve, B. Kieseier, H. Wiendl. (2007) Multiple sclerosis therapy: An update on recently finished trials. Journal of Neurology 254:11, 1473-1490
CrossRef368
Douglas S. Goodin, Louis D. Biermann, Saeed Bohlega, Alexey Boiko, Michel Chofflon, Souheil Gebeily, Riadh Gouider, Eva Havrdova, Gabor Jakab, Rana Karabudak, Dimitrios Karussis, Ariel Miller, Hossein Pakdaman, Krzysztof Selmaj, Mohammad Sharief. (2007) Integrating an evidence-based assessment of benefit and risk in disease-modifying treatment of multiple sclerosis. Current Medical Research and Opinion 23:11, 2823-2832
CrossRef369
Hisashi Oishi, Shinichi Mizuki, Miho Terada, Megumi Kudo, Kimi Araki, Masatake Araki, Masato Nose, Satoru Takahashi. (2007) Increased expression of soluble form of vascular cell adhesion molecule-1 aggravates autoimmune arthritis in MRL-Fas lpr mice. Pathology International 57:11, 734-740
CrossRef370
V. M. Anderson, J. W. Bartlett, N. C. Fox, L. Fisniku, D. H. Miller. (2007) Detecting treatment effects on brain atrophy in relapsing remitting multiple sclerosis: Sample size estimates. Journal of Neurology 254:11, 1588-1594
CrossRef371
Martina A McAteer, Nicola R Sibson, Constantin von zur Muhlen, Jurgen E Schneider, Andrew S Lowe, Nicholas Warrick, Keith M Channon, Daniel C Anthony, Robin P Choudhury. (2007) In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nature Medicine 13:10, 1253-1258
CrossRef372
Edward J. Fox, Timothy K. Vartanian, Scott S. Zamvil. (2007) The Immunogenicity of Disease-Modifying Therapies for Multiple Sclerosis: Clinical Implications for Neurologists. The Neurologist 13:6, 355-362
CrossRef373
Vissia Viglietta, Samia J. Khoury. (2007) Modulating co-stimulation. Neurotherapeutics 4:4, 666-675
CrossRef374
Hin Hin Ko, Brian Bressler. (2007) Natalizumab: pharmacology, clinical efficacy and safety in the treatment of patients with Crohn’s disease. Expert Review of Gastroenterology & Hepatology 1:1, 29-39
CrossRef375
Paolo A. Muraro, Bibiana Bielekova. (2007) Emerging therapies for multiple sclerosis. Neurotherapeutics 4:4, 676-692
CrossRef376
Richard A. Rudick, Deborah Miller, Steve Hass, Michael Hutchinson, Peter A. Calabresi, Christian Confavreux, Steven L. Galetta, Gavin Giovannoni, Eva Havrdova, Ludwig Kappos, Fred D. Lublin, David H. Miller, Paul W. O'Connor, J. Theodore Phillips, Chris H. Polman, Ernst-Wilhelm Radue, William H. Stuart, Andrzej Wajgt, Bianca Weinstock-Guttman, Daniel R. Wynn, Frances Lynn, Michael A. Panzara. (2007) Health-related quality of life in multiple sclerosis: effects of natalizumab. Annals of Neurology 62:4, 335-346
CrossRef377
Bernhard Hemmer, Hans-Peter Hartung. (2007) Toward the development of rational therapies in multiple sclerosis: what is on the horizon?. Annals of Neurology 62:4, 314-326
CrossRef378
T. Holmøy, F. Vartdal. (2007) The Immunological Basis for Treatment of Multiple Sclerosis. Scandinavian Journal of Immunology 66:4, 374-382
CrossRef379
Anna Williams, Gabrièle Piaton, Catherine Lubetzki. (2007) Astrocytes-Friends or foes in multiple sclerosis?. Glia 55:13, 1300-1312
CrossRef380
Henry F McFarland, Roland Martin. (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nature Immunology 8:9, 913-919
CrossRef381
A. Dressel, D. Mirowska-Guzel, C. Gerlach, F. Weber. (2007) Migration of T-cell subsets in multiple sclerosis and the effect of interferon-?1a. Acta Neurologica Scandinavica 116:3, 164-168
CrossRef382
Stuart D. Cook. (2007) Approved drugs and their problems in patient care: Routes of administration and dosing. Journal of the Neurological Sciences 259:1-2, 38-41
CrossRef383
Per Soelberg Sorensen. (2007) The gap between effect of drugs and effectiveness of treatments. Journal of the Neurological Sciences 259:1-2, 128-132
CrossRef384
Oscar Fernández. (2007) Combination therapy in multiple sclerosis. Journal of the Neurological Sciences 259:1-2, 95-103
CrossRef385
Oliver Neuhaus, Bernd C. Kieseier, Hans-Peter Hartung. (2007) Pharmacokinetics and pharmacodynamics of the interferon-betas, glatiramer acetate, and mitoxantrone in multiple sclerosis. Journal of the Neurological Sciences 259:1-2, 27-37
CrossRef386
C. Kleinschnitz, S.G. Meuth, B.C. Kieseier, H. Wiendl. (2007) Multiple-Sklerose-Update zur Pathophysiologie und neuen immuntherapeutischen Ansätzen. Der Nervenarzt 78:8, 883-911
CrossRef387
Bernadette Kalman, Karen Laitinen, Samuel Komoly. (2007) The involvement of mitochondria in the pathogenesis of multiple sclerosis. Journal of Neuroimmunology 188:1-2, 1-12
CrossRef388
Jeffrey I. Greenstein. (2007) Current concepts of the cellular and molecular pathophysiology of multiple sclerosis. Developmental Neurobiology 67:9, 1248-1265
CrossRef389
DeRen Huang, Michael Cossoy, Meizhang Li, Dean Choi, Alan Taege, Susan M. Staugaitis, Susan Rehm, Richard M. Ransohoff. (2007) Inflammatory progressive multifocal leukoencephalopathy in human immunodeficiency virus-negative patients. Annals of Neurology 62:1, 34-39
CrossRef390
Kenneth P. Johnson. (2007) Natalizumab (Tysabri) Treatment for Relapsing Multiple Sclerosis. The Neurologist 13:4, 182-187
CrossRef391
Michael P. Pender, Judith M. Greer. (2007) Immunology of multiple sclerosis. Current Allergy and Asthma Reports 7:4, 285-292
CrossRef392
Alessandro Lavagna, Massimiliano Bergallo, Marco Daperno, Raffaello Sostegni, Cristina Costa, Rosalia Leto, Lucia Crocellà, Giancarlo Molinaro, Rodolfo Rocca, Rossana Cavallo, Angelo Pera. (2007) Infliximab and the risk of latent viruses reactivation in active Crohn's disease. Inflammatory Bowel Diseases 13:7, 896-902
CrossRef393
R. Gold, A. Jawad, D.H. Miller, D.C. Henderson, A. Fassas, W. Fierz, H.P. Hartung. (2007) Expert opinion: Guidelines for the use of natalizumab in multiple sclerosis patients previously treated with immunomodulating therapies. Journal of Neuroimmunology 187:1-2, 156-158
CrossRef394
Ransohoff, Richard M., . (2007) Natalizumab for Multiple Sclerosis. New England Journal of Medicine 356:25, 2622-2629
Full Text395
William H. Stuart. (2007) Combination therapy for the treatment of multiple sclerosis: challenges and opportunities. Current Medical Research and Opinion 23:6, 1199-1208
CrossRef396
Fiona Costello, Olaf Stüve, Martin S Weber, Scott S Zamvil, Elliot Frohman. (2007) Combination therapies for multiple sclerosis: scientific rationale, clinical trials, and clinical practice. Current Opinion in Neurology 20:3, 281-285
CrossRef397
Mark A. Kroenke, Benjamin M. Segal. (2007) Th17 and Th1 responses directed against the immunizing epitope, as opposed to secondary epitopes, dominate the autoimmune repertoire during relapses of experimental autoimmune encephalomyelitis. Journal of Neuroscience Research 85:8, 1685-1693
CrossRef398
Bernd C Kieseier, Heinz Wiendl, Bernhard Hemmer, Hans-Peter Hartung. (2007) Treatment and treatment trials in multiple sclerosis. Current Opinion in Neurology 20:3, 286-293
CrossRef399
Dean M Wingerchuk, Claudia F Lucchinetti. (2007) Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis. Current Opinion in Neurology 20:3, 343-350
CrossRef400
Richard E Gonsette. (2007) Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis. Expert Opinion on Pharmacotherapy 8:8, 1103-1116
CrossRef401
R. John Looney, Betty Diamond, V. Michael Holers, Marc C. Levesque, Larry Moreland, Moon H. Nahm, E. William St. Clair. (2007) Guidelines for assessing immunocompetency in clinical trials for autoimmune diseases. Clinical Immunology 123:3, 235-243
CrossRef402
Brian G. Feagan. (2007) Medical Management of Ulcerative Colitis in 2006: What's on the Horizon?. The American Journal of Gastroenterology 102:s1, S7-S13
CrossRef403
Kenneth P. Johnson. (2007) Control of multiple sclerosis relapses with immunomodulating agents. Journal of the Neurological Sciences 256, S23-S28
CrossRef404
Ludwig Kappos, David Bates, Hans-Peter Hartung, Eva Havrdova, David Miller, Chris H Polman, Mads Ravnborg, Stephen L Hauser, Richard A Rudick, Howard L Weiner, Paul W O'Connor, John King, Ernst Wilhelm Radue, Tarek Yousry, Eugene O Major, David B Clifford. (2007) Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. The Lancet Neurology 6:5, 431-441
CrossRef405
Adrienne Boissy, Robert J. Fox. (2007) Current treatment options in multiple sclerosis. Current Treatment Options in Neurology 9:3, 176-186
CrossRef406
Simon F Lacey, Wendi Zhou. (2007) Immune responses to BK and JC viruses in immunocompromised patients. Future Virology 2:3, 255-266
CrossRef407
Oliver Neuhaus, Hans-Peter Hartung. (2007) Evaluation of atorvastatin and simvastatin for treatment of multiple sclerosis. Expert Review of Neurotherapeutics 7:5, 547-556
CrossRef408
Stephan R. Targan, Brian G. Feagan, Richard N. Fedorak, Bret A. Lashner, Remo Panaccione, Daniel H. Present, Martina E. Spehlmann, Paul J. Rutgeerts, Zsolt Tulassay, Miroslava Volfova, Douglas C. Wolf, Chito Hernandez, Jeffrey Bornstein, William J. Sandborn. (2007) Natalizumab for the Treatment of Active Crohn’s Disease: Results of the ENCORE Trial. Gastroenterology 132:5, 1672-1683
CrossRef409
Hans Lassmann. (2007) New concepts on progressive multiple sclerosis. Current Neurology and Neuroscience Reports 7:3, 239-244
CrossRef410
Michael Hutchinson. (2007) Natalizumab: A new treatment for relapsing remitting multiple sclerosis. Therapeutics and Clinical Risk Management 3:2, 259-268
CrossRef411
James B. Bussel, Lisa Giulino, Susan Lee, Vivek L. Patel, Christy Sandborg, E. Richard Stiehm. (2007) Update on Therapeutic Monoclonal Antibodies. Current Problems in Pediatric and Adolescent Health Care 37:4, 118-135
CrossRef412
Shumei Man, Eroboghene E. Ubogu, Richard M. Ransohoff. (2007) Inflammatory Cell Migration into the Central Nervous System: A Few New Twists on an Old Tale. Brain Pathology 17:2, 243-250
CrossRef413
Derek Soon, Daniel R. Altmann, Kryshani T.M. Fernando, Garin Giovannoni, Frederick Barkhof, Chris H. Polman, Paul O’Connor, Bruce Gray, Michael Panzara, David H. Miller. (2007) A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis. Journal of Neurology 254:3, 306-314
CrossRef414
Mathias Buttmann, Peter Rieckmann. (2007) Interferon-β 1b in multiple sclerosis. Expert Review of Neurotherapeutics 7:3, 227-239
CrossRef415
Olaf Stüve, Jeffrey L. Bennett. (2007) Pharmacological Properties, Toxicology and Scientific Rationale for the use of Natalizumab (Tysabri
) in Inflammatory Diseases. CNS Drug Reviews 13:1, 79-95
CrossRef416
Philip L. De Jager, David A. Hafler. (2007) New Therapeutic Approaches for Multiple Sclerosis. Annual Review of Medicine 58:1, 417-432
CrossRef417
Sheila A Doggrell. (2007) Is fingolimod an advancement in the treatment of multiple sclerosis?. Expert Opinion on Pharmacotherapy 8:3, 383-386
CrossRef418
John K MacDonald, John WD McDonald, John K MacDonald. 2007. Natalizumab for induction of remission in Crohn's disease. .
CrossRef419
David Miller. (2007) Multiple sclerosis: new insights and therapeutic progress. The Lancet Neurology 6:1, 5-6
CrossRef420
Eric H Liu, Richard M Siegel, David M Harlan, John J O'Shea. (2007) T cell–directed therapies: lessons learned and future prospects. Nature Immunology 8:1, 25-30
CrossRef421
Thomas M. Zollner, Khusru Asadullah, Michael P. Schön. (2007) Targeting leukocyte trafficking to inflamed skin - still an attractive therapeutic approach?. Experimental Dermatology 16:1, 1-12
CrossRef422
A. Verma. (2007) A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. Yearbook of Neurology and Neurosurgery 2007, 82-84
CrossRef423
Bernd C Kieseier, Heinz Wiendl. (2007) Oral Disease-Modifying Treatments for Multiple Sclerosis. CNS Drugs 21:6, 483-502
CrossRef424
Paul O’Connor. (2007) Natalizumab and the role of α 4 -integrin antagonism in the treatment of multiple sclerosis. Expert Opinion on Biological Therapy 7:1, 123-136
CrossRef425
Amer Jaber, Reinoud Driebergen, Gavin Giovannoni, Huub Schellekens, James Simsarian, Michele Antonelli. (2007) The Rebif® New Formulation Story. Drugs in R & D 8:6, 335-348
CrossRef426
David Ramos-Barbón. (2007) Asma. Archivos de Bronconeumología 43, 3-14
CrossRef427
Bernd C. Kieseier, Hans-Peter Hartung. (2007) Interferon-β and neuroprotection in multiple sclerosis—Facts, hopes and phantasies. Experimental Neurology 203:1, 1-4
CrossRef428
Lucienne Chatenoud. (2006) Immune therapies of autoimmune diseases: are we approaching a real cure?. Current Opinion in Immunology 18:6, 710-717
CrossRef429
, Peter Rieckmann. (2006) Immunmodulatorische Stufentherapie der Multiplen Sklerose. Der Nervenarzt 77:12, 1506-1518
CrossRef430
Simone Ferrero, Francesca Esposito, Stefano Pretta, Nicola Ragni. (2006) Fetal risks related to the treatment of multiple sclerosis during pregnancy and breastfeeding. Expert Review of Neurotherapeutics 6:12, 1823-1831
CrossRef431
M. Krakauer, P.S. Sorensen, F. Sellebjerg. (2006) CD4+ memory T cells with high CD26 surface expression are enriched for Th1 markers and correlate with clinical severity of multiple sclerosis. Journal of Neuroimmunology 181:1-2, 157-164
CrossRef432
Natalia M Rebenko-Moll, LiPing Liu, Astrid Cardona, Richard M Ransohoff. (2006) Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the details. Current Opinion in Immunology 18:6, 683-689
CrossRef433
Jason Witherington, Emma L. Blaney, Vincent Bordas, Richard L. Elliott, Alessandra Gaiba, Neil Garton, Philip M. Green, Antoinette Naylor, David G. Smith, David J. Spalding, Andrew K. Takle, Robert W. Ward. (2006) Pyridone derivatives as potent, orally bioavailable VLA-4 integrin antagonists. Bioorganic & Medicinal Chemistry Letters 16:21, 5538-5541
CrossRef434
Robert Weissert. (2006) The curtain is drawn for both natalizumab and fingolimod (FTY720): a new era of multiple sclerosis therapy has arrived. Expert Review of Neurotherapeutics 6:11, 1587-1590
CrossRef435
Allen J. Aksamit. (2006) Review of Progressive Multifocal Leukoencephalopathy and Natalizumab. The Neurologist 12:6, 293-298
CrossRef436
Mike Boggild. (2006) Rationale and experience with combination therapies in multiple sclerosis. Journal of Neurology 253:S6, vi45-vi51
CrossRef437
Peter Vanderslice, Darren G Woodside. (2006) Integrin antagonists as therapeutics for inflammatory diseases. Expert Opinion on Investigational Drugs 15:10, 1235-1255
CrossRef438
Paulus Mrass, Wolfgang Weninger. (2006) Immune cell migration as a means to control immune privilege: lessons from the CNS and tumors. Immunological Reviews 213:1, 195-212
CrossRef439
Michael Sixt, Martina Bauer, Tim Lämmermann, Reinhard Fässler. (2006) β1 integrins: zip codes and signaling relay for blood cells. Current Opinion in Cell Biology 18:5, 482-490
CrossRef440
Mark S Freedman. (2006) Disease-modifying drugs for multiple sclerosis: current and future aspects. Expert Opinion on Pharmacotherapy 7:s1, S1-S9
CrossRef441
Elliot Frohman, Fiona Costello, Robert Zivadinov, Olaf Stuve, Amy Conger, Heather Winslow, Anand Trip, Teresa Frohman, Laura Balcer. (2006) Optical coherence tomography in multiple sclerosis. The Lancet Neurology 5:10, 853-863
CrossRef442
Arnaud Charil, Tarek A Yousry, Marco Rovaris, Frederik Barkhof, Nicola De Stefano, Franz Fazekas, David H Miller, Xavier Montalban, Jack H Simon, Chris Polman, Massimo Filippi. (2006) MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”. The Lancet Neurology 5:10, 841-852
CrossRef443
R Philip Kinkel. (2006) Interferon-β 1a : a once-weekly immunomodulatory treatment for patients with multiple sclerosis. Expert Review of Clinical Immunology 2:5, 691-704
CrossRef444
Martin Stangel. (2006) Does natalizumab have a role in the treatment of relapsing multiple sclerosis?. Nature Clinical Practice Neurology 2:9, 476-477
CrossRef445
William W. Agace. (2006) Tissue-tropic effector T cells: generation and targeting opportunities. Nature Reviews Immunology 6:9, 682-692
CrossRef446
T. B. Y. Liem. (2006) Wat kunnen we leren uit de ervaringen met natalizumab bij de behandeling van multiple sclerose?. Medisch-Farmaceutische Mededelingen 44:9, 258-259
CrossRef447
Laura Airas, Jari Mikkola, Jani M. Vainio, Irina Elovaara, David J. Smith. (2006) Elevated serum soluble vascular adhesion protein-1 (VAP-1) in patients with active relapsing remitting multiple sclerosis. Journal of Neuroimmunology 177:1-2, 132-135
CrossRef448
Yi-Yang Yvonne Li, H Daniel Perez, Thomas M Zollner. (2006) Fatalities in natalizumab treatment - a 'no go for leukocyte recirculation approaches?. Expert Opinion on Therapeutic Targets 10:4, 489-499
CrossRef449
David-Axel Laplaud, Laureline Berthelot, Patrick Miqueu, Kasia Bourcier, Julien Moynard, Yannick Oudinet, Marina Guillet, Catherine Ruiz, Neal Oden, Sophie Brouard, Charles R.G. Guttmann, Howard L. Weiner, Samia J. Khoury, Jean-Paul Soulillou. (2006) Serial blood T cell repertoire alterations in multiple sclerosis patients; correlation with clinical and MRI parameters. Journal of Neuroimmunology 177:1-2, 151-160
CrossRef450
JK MacDonald, JWD McDonald, John MacDonald. 2006. Natalizumab for induction of remission in Crohn's disease. .
CrossRef451
Lawrence Steinman, Scott S. Zamvil. (2006) How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Annals of Neurology 60:1, 12-21
CrossRef452
Richard A. Rudick. (2006) Disease modification in multiple sclerosis: Issues with relevance to clinical trial designs in Alzheimer’s disease. Alzheimer's and Dementia 2:3, 143-146
CrossRef453
(2006) Natalizumab for Relapsing Multiple Sclerosis. New England Journal of Medicine 354:22, 2387-2389
Full Text454
Olaf Stüve, Christina M. Marra, Keith R. Jerome, Linda Cook, Petra D. Cravens, Sabine Cepok, Elliot M. Frohman, J. Theodore Phillips, Gabriele Arendt, Bernhard Hemmer, Nancy L. Monson, Michael K. Racke. (2006) Immune surveillance in multiple sclerosis patients treated with natalizumab. Annals of Neurology 59:5, 743-747
CrossRef455
Stephen L. Hauser, Howard L. Weiner. (2006) Natalizumab: Immune effects and implications for therapy. Annals of Neurology 59:5, 731-732
CrossRef456
Bernhard Hemmer, Stefan Nessler, Dun Zhou, Bernd Kieseier, Hans-Peter Hartung. (2006) Immunopathogenesis and immunotherapy of multiple sclerosis. Nature Clinical Practice Neurology 2:4, 201-211
CrossRef457
Sylvia Delgado, William A. Sheremata. (2006) The role of CD4+ T-cells in the development of MS. Neurological Research 28:3, 245-249
CrossRef458
Frank Clancy. (2006) FDA PANELISTS OFFER INSIDE TRACK TO DECISION ON NATALIZUMAB. Neurology Today 6:8, 1
CrossRef459
Ropper, Allan H., . (2006) Selective Treatment of Multiple Sclerosis. New England Journal of Medicine 354:9, 965-967
Full Text460
Rudick, Richard A., Stuart, William H., Calabresi, Peter A., Confavreux, Christian, Galetta, Steven L., Radue, Ernst-Wilhelm, Lublin, Fred D., Weinstock-Guttman, Bianca, Wynn, Daniel R., Lynn, Frances, Panzara, Michael A., Sandrock, Alfred W., . (2006) Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis. New England Journal of Medicine 354:9, 911-923
Full Text461
Yousry, Tarek A., Major, Eugene O., Ryschkewitsch, Caroline, Fahle, Gary, Fischer, Steven, Hou, Jean, Curfman, Blanche, Miszkiel, Katherine, Mueller-Lenke, Nicole, Sanchez, Esther, Barkhof, Frederik, Radue, Ernst-Wilhelm, Jäger, Hans R., Clifford, David B., . (2006) Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy. New England Journal of Medicine 354:9, 924-933
Full Text462
Amy Waldman, Erin O'Connor, Gihan Tennekoon. (2006) Childhood multiple sclerosis: A review. Mental Retardation and Developmental Disabilities Research Reviews 12:2, 147-156
CrossRef463
Orla Gray, Gavin V McDonnell, Raeburn B Forbes, Orla Gray. 2003. Intravenous immunoglobulins for multiple sclerosis. .
CrossRef
- Letters
