Original Article
Maintenance Therapy with Certolizumab Pegol for Crohn's Disease
N Engl J Med 2007; 357:239-250July 19, 2007
- Abstract
Background
Certolizumab pegol is a pegylated humanized Fab′ fragment with a high binding affinity for tumor necrosis factor α that does not induce apoptosis of T cells or monocytes.
Methods
In our randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol maintenance therapy in adults with moderate-to-severe Crohn's disease. As induction therapy, 400 mg of certolizumab pegol was administered subcutaneously at weeks 0, 2, and 4. Patients with a clinical response (defined as reduction of at least 100 from the baseline score on the Crohn's Disease Activity Index [CDAI]) at week 6 were stratified according to their baseline C-reactive protein level and were randomly assigned to receive 400 mg of certolizumab pegol or placebo every 4 weeks through week 24, with follow-up through week 26.
Results
Among patients with a response to induction therapy at week 6 (428 of 668 [64%]), the response was maintained through week 26 in 62% of patients with a baseline C-reactive protein level of at least 10 mg per liter (the primary end point) who were receiving certolizumab pegol (vs. 34% of those receiving placebo, P<0.001) and in 63% of patients in the intention-to-treat population who were receiving certolizumab pegol (vs. 36% receiving placebo, P<0.001). Among patients with a response to induction therapy at week 6, remission (defined by a CDAI score of ≤150) at week 26 was achieved in 48% of patients in the certolizumab group and 29% of those in the placebo group (P<0.001). The efficacy of certolizumab pegol was also shown in patients taking and those not taking glucocorticoids or immunosuppressants and in patients who had and those who had not previously taken infliximab. Infectious serious adverse events (including one case of pulmonary tuberculosis) occurred in 3% of patients receiving certolizumab pegol and in less than 1% of patients receiving placebo. Antinuclear antibodies developed in 8% of the patients in the certolizumab group; antibodies against certolizumab pegol developed in 9% of all patients who entered the induction phase.
Conclusions
Patients with moderate-to-severe Crohn's disease who had a response to induction therapy with 400 mg of certolizumab pegol were more likely to have a maintained response and a remission at 26 weeks with continued certolizumab pegol treatment than with a switch to placebo. (ClinicalTrials.gov number, NCT00152425.)
Media in This Article
Figure 1
Enrollment, Group Assignments, and Follow-up.Figure 2
Efficacy of Maintenance Therapy with Certolizumab Pegol in Patients with a Response to Induction Therapy at Week 6.Article Activity
- Article
The proinflammatory cytokine tumor necrosis factor α (TNF-α) is highly expressed in the blood, colonic tissue, and stool of patients with Crohn's disease.1-4 Infliximab and adalimumab are engineered IgG1 monoclonal antibodies that bind to TNF-α (the first represents a chimeric molecule and the latter has been derived from human origin) and are effective in the induction and maintenance of response and remission in patients with Crohn's disease.5-7 The efficacy of infliximab in the treatment of Crohn's disease has been attributed to multiple mechanisms, including reverse signaling through membrane-bound TNF-α and the induction of apoptosis of T cells and monocytes.8-11
Certolizumab pegol, a pegylated humanized Fab′ fragment of an anti–TNF-α monoclonal antibody, has several characteristics that differentiate it from infliximab and adalimumab. In vitro, certolizumab pegol has a higher affinity for TNF-α, is devoid of the Fc portion of the antibody, and does not induce complement activation, antibody-dependent cellular cytotoxicity, or apoptosis.11-13 One study by our group14 suggested that induction treatment with certolizumab pegol might be effective for the treatment of moderate-to-severe active Crohn's disease: a 400-mg dose of certolizumab pegol every 4 weeks was effective in patients with a serum C-reactive protein (CRP) level of at least 10 mg per liter; response rates at week 12 were significantly higher than those in the placebo group. In that study, however, we did not prospectively stratify patients according to CRP level; such stratification occurred later in the clinical trial program.
The Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy 1 (PRECISE 1) trial involved a placebo-controlled induction phase and a 26-week treatment phase in a population of patients with active Crohn's disease; it is reported on elsewhere in this issue of the Journal.15 PRECISE 2, which we present in this article, was a 26-week trial involving maintenance and withdrawal therapy with certolizumab pegol in patients with moderate-to-severe Crohn's disease who were selected for having a response to open-label induction therapy.
Methods
A committee of academic investigators and UCB Pharma scientists (the Study Advisory Board) designed the study. Data were collected by a contract research organization (ICON Clinical Research) and analyzed by the sponsor and external experts. The academic authors vouch for the veracity and completeness of the data and data analyses presented. Both the academic and industry authors wrote the first and subsequent drafts of the manuscript and hold the data, and the decision to publish was made by an academic author.
Patients
Our multicenter, randomized, double-blind, placebo-controlled trial was conducted worldwide at 147 centers, from February 2004 until May 2005. The protocol was approved by the institutional review board or ethics committee at each center. All patients gave written informed consent.
Adults were eligible if they had a 3-month history of active Crohn's disease, defined as a Crohn's Disease Activity Index (CDAI) score of 220 to 450.16 The CDAI is a weighted, composite index of eight items (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extraintestinal manifestations or fistula, use or nonuse of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight), with scores ranging from 0 to 600 and higher scores indicating more severe disease activity. Permitted concomitant therapies for Crohn's disease were stable doses of 5-aminosalicylates, 30 mg or less of prednisolone per day (or equivalent), azathioprine, 6-mercaptopurine, methotrexate, and antibiotics. Exclusion criteria were the presence of the short-bowel syndrome, ostomy, obstructive symptoms with strictures, abscess, history of tuberculosis, positive chest radiograph, positive tuberculin purified-protein-derivative (PPD) skin test, demyelinating disease, and cancer. (Exclusion criteria did not include a positive PPD skin test in combination with previous vaccination with bacille Calmette–Guérin and a negative chest radiograph.) Patients who had received any certolizumab pegol, who had received an anti-TNF agent or other biologic therapy within 3 months before enrollment, or who had a severe hypersensitivity reaction or no clinical response after initial dosing with an anti-TNF were also excluded. Reasons for discontinuation of any previous anti-TNF treatment were not reported.
Study Design
Eligible patients received induction therapy, consisting of subcutaneous injections of 400 mg of certolizumab pegol at weeks 0, 2, and 4. A clinical response was defined as a reduction of at least 100 from the baseline score on the CDAI; remission was defined as a CDAI score of 150 points or less.16 Patients who had a response to induction therapy at week 6 were randomly assigned to receive 400 mg of certolizumab pegol (certolizumab group) or placebo (placebo group) at weeks 8, 12, 16, 20, and 24 and were followed through week 26. The study was centrally randomized, and group assignment was stratified according to serum CRP level (≥10 mg per liter or <10 mg per liter), concurrent use of glucocorticoids (yes or no), and concurrent use of immunosuppressive agents (yes or no). The randomization code consisted of eight separate lists (one for each stratum) and was generated by an independent contractor. Randomization was centralized by means of an interactive voice-recognition system. Patients and investigators were unaware of the group assignment.
Doses of concomitant medications were kept constant except for those of glucocorticoids, for which the dose could be reduced but no forced tapering was required. Any escalation of dose above baseline levels qualified as a failure of therapy.
Follow-up and Efficacy and Safety Evaluations
Patients were followed up at weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, and 26. At each visit, diary data were collected, clinical assessments of Crohn's disease were undertaken, adverse events and the use of concomitant medications were recorded, and laboratory samples were collected. Data for determining the CDAI score were collected for 7 days by means of a diary card completed daily by the patient. Safety evaluations included the checking of vital signs, physical examinations, hematologic analysis, serum biochemistry tests, and urinalysis. Antibodies against certolizumab pegol were assayed with the use of previously published methods, with a lower detection limit of 2.4 U per milliliter (an increase by a factor of 2 over the level in a reference population).17 CRP measurements were made at a central laboratory (MDS Pharma Services, Central Lab) (normal range, 0 to 4 mg per liter). The health-related quality of life was assessed at weeks 0, 6, 16, and 26 with the use of the Inflammatory Bowel Disease Questionnaire, scores for which range from 32 to 224, with higher scores indicating a better quality of life.18
Statistical Analysis
The primary end point was a clinical response at week 26 in patients with a baseline CRP level of at least 10 mg per liter. Secondary end points included response at week 26, remission at week 26 in the intention-to-treat population, and remission in the group with a baseline CRP level of at least 10 mg per liter. If patients received rescue therapy during the study, their treatment was considered to have failed, starting at the time of the administration of the first rescue therapy. The intention-to-treat population included all patients who were randomly assigned to a study group, who received at least one injection of certolizumab pegol or placebo, and who had at least one efficacy evaluation after the first double-blind injection.
Percentages of patients having a response or remission were compared between the two study groups with the use of logistic regression (with adjustment for geographic region, use of glucocorticoids, use of immunosuppressive agents, and baseline CRP level in the intention-to-treat population only). A closed test procedure was used to control for multiple comparisons across secondary end points.19 A two-sided significance level of 0.05 was used in all comparisons. Hypothesis testing of major secondary variables was performed only if the primary end point was significant. Baseline characteristics were compared between the two study groups with the use of either the chi-square test or Fisher's exact test for categorical variables or analysis of variance for continuous variables. Safety variables were compared between the two groups with the use of Fisher's exact test. All efficacy analyses were performed according to the intention-to-treat principle. Post hoc analyses were performed to determine the CDAI scores with the last observation carried forward for each visit and to explore the effect of certolizumab pegol as compared with placebo in subpopulations receiving concomitant glucocorticoids, receiving concomitant immunosuppressants, or that previously received infliximab.
We anticipated that 55% of 712 patients receiving induction treatment with certolizumab pegol would have a response at week 6. We calculated that the random assignment of 392 patients who had a response (196 patients with a CRP level ≥10 mg per liter and 196 with a CRP level <10 mg per liter) would result in a statistical power of 80% to detect a difference in the response rate during the maintenance phase, assuming a rate of 45% in the certolizumab group and 25% in the placebo group.
Results
Patients
Figure 1Figure 1
Enrollment, Group Assignments, and Follow-up. shows the disposition of the study patients. Baseline demographic and disease characteristics were similar in the two study groups. Twenty-four percent (103 of 425) of patients in the intention-to-treat population had previously received infliximab (Table 1Table 1
Demographic and Disease Characteristics of Patients in the Intention-to-Treat Population, According to Type of Maintenance Therapy.).Efficacy
Response to Induction at Week 6
At week 6 (after three 400-mg doses of certolizumab pegol), 64% of patients (428 of 668) had a response and 43% (289 of 668) had a remission. The remaining 36% of patients who did not have a response (240 of 668) were not followed further for efficacy analyses.
Primary End Point
In total, 213 patients (32% of the 668 patients who entered the induction phase and 50% of the 428 who had a response to induction therapy) had a baseline serum CRP level of at least 10 mg per liter. During the maintenance phase, of these 213 patients, 62% in the certolizumab group (69 of 112) had a response at week 26, as compared with 34% in the placebo group (34 of 101) (P<0.001) (Figure 2AFigure 2
Efficacy of Maintenance Therapy with Certolizumab Pegol in Patients with a Response to Induction Therapy at Week 6.).Secondary End Points
Of the 428 patients in the intention-to-treat population who had a response to induction therapy at week 6, 63% in the certolizumab group (135 of 215) also had a response at week 26, as compared with 36% (76 of 210) in the placebo group (P<0.001) (Figure 2B). The difference in response between treatment with certolizumab pegol and treatment with placebo was sustained throughout the maintenance phase, and the magnitude of the difference was similar in the intention-to-treat population and in patients with a baseline CRP serum level of at least 10 mg per liter (Figure 2C). The response rate during the maintenance phase of 63% of patients in the intention-to-treat population who had a response to induction therapy at week 6 is equivalent to a combined response rate during the induction and maintenance phases of 40% (with a combined remission rate of 31%) in the 668 patients who entered the induction phase.
Among all patients in the intention-to-treat population who had a response at week 6, remission rates at week 26 were 48% (103 of 215) in the certolizumab group and 29% (60 of 210) in the placebo group (P<0.001) (Figure 2D). In the subgroup with baseline CRP serum levels of at least 10 mg per liter, remission rates at week 26 were 42% (47 of 112) in the certolizumab group and 26% (26 of 101) in the placebo group (P=0.01) (Figure 2D). Figure 2E depicts the results of an exploratory analysis, showing a reduction of the median CDAI scores in the intention-to-treat population after induction therapy with certolizumab pegol and the gradual rise in disease activity during the maintenance phase in the placebo group, as compared with the certolizumab group.
Fourteen percent of patients in the intention-to-treat population who had a response to induction therapy with certolizumab pegol (58 of 425) had draining fistulas at baseline (28 patients in the certolizumab group and 30 patients in the placebo group). During the study, of the 58 patients, 54% (15 of 28 patients) in the certolizumab group had fistula closure (defined as the absence of drainage on gentle compression at any two consecutive post-baseline visits at least 3 weeks apart), as compared with 43% (13 of 30) in the placebo group.
Among patients who had a response to induction therapy, a significantly greater percentage of patients in the certolizumab group (60% [129 of 214 patients]) also had a response as measured with the use of the Inflammatory Bowel Disease Questionnaire (an increase in the total score of at least 16 points) at week 26, as compared with those in the placebo group (43% [90 of 210 patients]) (P<0.001). Mean scores on the questionnaire were 123 at week 0 and 175 at week 6 among patients in the intention-to-treat population; during the maintenance phase, at week 16 mean scores were 169 in the certolizumab group and 158 in the placebo group and at week 26 they were 176 and 168, respectively. Adjusted mean scores were 170 in the certolizumab group and 162 in the placebo group (P=0.008) at week 16 and 171 and 163 (P=0.007), respectively, at week 26.
Exploratory Analyses
In the intention-to-treat population, response rates at week 26 were significantly greater among patients receiving maintenance therapy with certolizumab pegol than among those receiving placebo, both for patients receiving concomitant immunosuppressive agents (61% [53 of 87] vs. 33% [28 of 86], P<0.001) and those not receiving concomitant immunosuppressive agents (64% [82 of 128] vs. 39% [48 of 124], P<0.001). A significant difference in the response rates at week 26 between the certolizumab group and the placebo group was found for patients who had previously received infliximab (44% [23 of 52] vs. 25% [13 of 51], P=0.02) and those who had not previously received infliximab (69% [112 of 163] vs. 40% [63 of 159], P<0.001). Neither the response rate nor the remission rate differed significantly between the two groups for patients who were and those who were not receiving concomitant glucocorticoids, immunosuppressive agents, or both.
For rates of response and remission, there were no significant interactions between group assignment and smoking status or body-mass index. A response was maintained at 26 weeks in 56% of current smokers (36 of 64 patients) in the certolizumab group and 34% in the placebo group (26 of 76 patients).
Among patients with a baseline CRP serum level of less than 10 mg per liter, response rates at week 26 were significantly greater in the certolizumab group (64% [66 of 103]) than in the placebo group (39% [42 of 109], P<0.001). Remission rates were 54% (56 of 103 patients) in the certolizumab group, as compared with 31% (34 of 109 patients) in the placebo group (P<0.001).
Safety
Serious adverse events occurred in 6% (12 of 216) of patients in the certolizumab group and 7% (14 of 212) of those in the placebo group (Table 2Table 2
Summary of Adverse Events in the Safety Population.). Serious infection occurred in 3% (6 of 216) of patients in the certolizumab group and in less than 1% (2 of 212) of patients in the placebo group. The most frequently reported adverse events were similar in the two groups. One patient died of an accidental fentanyl overdose during the open-label phase of this trial. No deaths, solid-organ or hematologic cancers, demyelinating diseases, or lupus occurred during the maintenance phase. Despite the absence of a reaction to the PPD skin test at screening, one patient treated with five doses of certolizumab pegol and concomitant azathioprine had pulmonary tuberculosis, which responded to standard combination therapy with antibiotics. One or more local reactions to injection occurred in 3% (6 of 216) of patients in the certolizumab group and 15% (31 of 212) of patients in the placebo group (Table 2).Autoimmune Antibodies
Among patients for whom values were available at both the baseline visit and the final visit, new antinuclear antibodies developed in 8% (16 of 192) of patients receiving certolizumab pegol and in 1% (2 of 178) of patients receiving placebo. New antibodies against double-stranded DNA developed in 1% (2 of 192) of patients in the certolizumab group and in 1% (1 of 178) of patients in the placebo group.
Antibodies against Certolizumab Pegol
Of the 668 patients who entered the induction phase, 58 (9%) had detectable antibodies against certolizumab pegol at some point during the study (Table 3Table 3
Summary of Data on Antibodies against Certolizumab Pegol, According to Use of Immunosuppressive Agents.). Three of the four patients in whom antibodies developed during the induction phase were randomly assigned to receive maintenance therapy, one with certolizumab pegol and two with placebo. In the remaining 54 patients, antibodies developed during the maintenance phase. Eighty percent of the antibodies were neutralizing antibodies. Rates of antibody formation were low in patients who received concomitant immunosuppressive agents and in those who received continuous therapy with certolizumab pegol (during the induction and maintenance phases) (Table 3).The presence of certolizumab pegol in vivo may have interfered with the antibody assay because it can form complexes with drug antibodies. Therefore, in analyses of data for the certolizumab group during the maintenance phase, we also used a reduced-trough plasma certolizumab pegol level as an indirect measure of the presence of antibodies. The number of patients who were positive for antibodies against certolizumab pegol increased from the 17 detected with the use of the assay to 21. As a result, the number of patients who may have had false negative results on the antibody assay, owing to interference by circulating levels of certolizumab pegol forming complexes with drug antibodies, was low. Of the 17 patients with positive tests for antibodies against certolizumab pegol, 12 (71%) had a response through week 26, as compared with 121 of 196 patients (62%) with negative tests for the antibodies.
Discussion
The results of our trial show that continued administration of certolizumab pegol subcutaneously every 4 weeks is superior to administration of placebo in the 64% of our patients with moderate-to-severe active Crohn's disease (despite the use of conventional treatments) who had a response to 6 weeks of induction therapy with 400 mg of certolizumab pegol (given at weeks 0, 2, and 4). The combined response rate during the induction and maintenance phases was 40%. However, the open-label study design results in an overestimation of the rate of induction of a response, and response rates to placebo are substantial among patients with Crohn's disease. Contrary to a finding in a previous phase 2 study,14 continued treatment with certolizumab pegol was equally effective in patients with high baseline CRP serum levels and those with low levels, and the response rate at week 26 did not depend on the baseline CRP level. Long-term improvement in the health-related quality of life was greater in the certolizumab group than in the placebo group. Antinuclear antibodies developed in 8% of patients treated with certolizumab pegol, an incidence that does not exceed that in healthy persons.20 Antibodies to certolizumab pegol developed in 9% of patients.
Since only 14% of patients had draining fistulas and inclusion in the study was based primarily on the overall disease activity, our trial was not powered to examine the efficacy of certolizumab pegol for fistula closure. Additional studies will be required to address this issue.
Our results also show that certolizumab pegol was effective in patients who had previously taken infliximab. The efficacy of maintenance treatment with certolizumab pegol was also seen in patients with and those without concomitant therapy with immunosuppressants. The development of antibodies against certolizumab pegol during the maintenance phase differed modestly between patients receiving and those not receiving concomitant immunosuppressive agents (2% vs. 12% in the certolizumab group and 8% vs. 24% in the placebo group).
Maintenance therapy with certolizumab pegol was associated with a safety profile that was consistent with profiles in previous studies.14,17,21,22 Two patients in the placebo group and six in the certolizumab group had serious adverse events consisting of infection, including one case of pulmonary tuberculosis. No solid-organ or hematologic cancers, demyelinating disease, or lupus were reported during the maintenance phase. With regard to the patient who died of a fentanyl overdose, to our knowledge there is no specific interaction between fentanyl and certolizumab pegol. Ongoing follow-up of patients in open-label treatment programs has not resulted in any new safety signals to date. Longer-term exposure of large cohorts of patients will be required to better characterize the adverse events associated with certolizumab pegol.
In conclusion, patients with moderate-to-severe active Crohn's disease who had a response to induction therapy with certolizumab pegol and continued to receive certolizumab pegol as maintenance therapy were more likely to have a maintained response and remission at 26 weeks than were those who switched to placebo.
Supported by a research grant from UCB Pharma and a research grant for infrastructure from the German Federal Ministry of Education and Research (BMBF) Competence Network Inflammatory Bowel Disease.
Dr. Schreiber reports receiving consulting fees from Abbott Laboratories, Bayer, Berlex/Schering, Boehringer Ingelheim, Bristol-Myers Squibb, Centocor, Elan Pharmaceuticals, Otsuka America Pharmaceuticals, Schering Pharma, Schering-Plough and its subsidiary Essex Pharma Solvay, Teva Pharmaceuticals, and UCB Pharma; serving as an unpaid consultant for Chemocentryx; receiving lecture fees from AstraZeneca, Abbott Laboratories, Essex–Schering-Plough, Dr. Falk Pharma, Ferring, Genizon, and UCB Pharma; receiving grant support from AstraZeneca, Berlex/Schering, and UCB Pharma; holding stock in Conaris Research Institute; and serving on the scientific advisory board of Applied Biosystems (Applera). Dr. Lawrance reports serving as an unpaid consultant for UCB Pharma. Dr. Thomsen reports receiving consulting fees from Ferring, Pfizer, and UCB Pharma; lecture fees from AstraZeneca, Dr. Falk Pharma, Ferring, Otsuka America Pharmaceuticals, and UCB Pharma; and serving as an investigator for AstraZeneca, Elan, Ferring, InDex Pharmaceuticals, Otsuka America Pharmaceuticals, and UCB Pharma. Dr. Hanauer reports receiving grant support from Abbott Laboratories, Asahi, UCB Pharma, Centocor, Elan, Genentech, Otsuka America Pharmaceuticals, PDL BioPharma, Prometheus, Targacept, and Therakos; receiving consulting fees from Abbott Laboratories, Amgen, Asahi, UCB Pharma, Centocor, Elan, Genentech, GlaxoSmithKline, Novartis, Otsuka America Pharmaceuticals, PDL BioPharma, Targacept, Teva Pharmaceuticals, and Therakos; serving on speaker's bureaus of UCB Pharma and Centocor; and receiving travel grants from Centocor. Dr. McColm and Mr. Bloomfield report being employees of UCB Pharma. Dr. Sandborn reports receiving grant support from Abbott Laboratories, Bristol-Myers Squibb, Centocor, Otsuka America Pharmaceuticals, PDL BioPharma, Procter & Gamble, Shire Pharmaceuticals, and UCB Pharma; receiving consulting fees from Abbott Laboratories, ActoGeniX, AGI Therapeutics, Alba Therapeutics, Alizyme, Alza, AstraZeneca, Avidia, Berlex, Bexel Pharmaceuticals, BioBalance, Bristol-Myers Squibb, Celegene, Centocor, Cerimon Pharmaceuticals, Chemocentryx, CombinatoRx, CoMentis, Corautus Genetics, Cosmo Technologies, Effective Pharmaceuticals, Eisai Medical Research, Elan Pharmaceuticals, Enzo Therapeutics, Eurand, FlexPharm, Genentech, GlaxoSmithKline, Hoffmann–La Roche, Hutchison Medipharma, Inflabloc Pharmaceuticals, Inotek Pharmaceuticals, Isis Pharmaceuticals, Jacobus Pharmaceutical, LigoCyte Pharmaceuticals, Medarex, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceutical, Novartis, NPS Pharmaceuticals, Ocera Therapeutics, Ono Pharma USA, PDL BioPharma, Pfizer, Sandwich, Procter & Gamble, Prometheus Laboratories, Renovis, Salix Pharmaceuticals, Schering-Plough, Shire Pharmaceuticals, Synta Pharmaceuticals, Teva Pharmaceuticals, Therakos, UCB Pharma, and ViaCell; and participating in continuing-medical-education events sponsored by Abbott Laboratories, Axcan Pharmaceuticals, AstraZeneca, Centocor, Elan Pharmaceuticals, Dr. Falk Pharma, Otsuka America Pharmaceuticals, PDL BioPharma, Procter & Gamble, Prometheus Laboratories, Salix Pharmaceuticals, Schering-Plough, Shire Pharmaceuticals, and UCB Pharma. No other potential conflict of interest relevant to this article was reported.
Source Information
From the Hospital for General Internal Medicine, Christian Albrechts University, Kiel, Germany (S.S.); Dalhousie University, Halifax, NS, Canada (M.K.-K.); School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Australia (I.C.L.); Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark (O.O.T.), Section of Gastroenterology and Nutrition, University of Chicago Medical Center, Chicago (S.B.H.); UCB Pharma, Slough, Berkshire, United Kingdom (J.M., R.B.); and Division of Gastroenterology, Mayo Clinic, Rochester, MN (W.J.S.).
Address reprint requests to Dr. Schreiber at the Klinik für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Schittenhelmstr. 12, Kiel 24105, Germany, or at s.schreiber@mucosa.de.
The Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy 2 (PRECISE 2) investigators are listed in the Appendix.
Appendix
The following investigators participated in the PRECISE 2 trial: Australia: Flinders Medical Centre, Bedford Park — P. Bampton; Alfred Hospital, Melbourne — F. Dudley; Royal Adelaide Hospital, Adelaide — D. Hetzel; Fremantle Hospital, Fremantle — I.C. Lawrance; Canberra Hospital, Garran — P. Pavli; Royal Prince Alfred Hospital Medical Centre, Newtown — W. Selby; Canada: Liver and Intestinal Research Centre, Vancouver, BC — F. Anderson; Health Sciences Centre, Winnipeg, MB — C. Bernstein; Sir Mortimer B. Davis–Jewish General Hospital, Montreal — A. Cohen; St. Paul's Hospital, Vancouver, BC — R. Enns; Mount Sinai Hospital, Toronto — G. Greenberg; Dalhousie University, Halifax, NS — M. Khaliq-Kareemi; Centre Hospitalier Regionale de Lanaudiere, Quebec, QC — P. Laflamme; Denmark: Glostrup Hospital, Glostrup — P. Bytzer; Aarhus Hospital, Aarhus C — J.F. Dahlerup; Vejle Hospital, Vejle — E. Ejlersen; Aalborg Hospital, Aalborg — J. Fallingborg; Gentofte Hospital, Hellerup — E. Langholz; Odense University Hospital, Odense — K. Lauritsen; Hvidovre Hospital, Hvidovre — A. Mertz-Nielsen; Bispebjerg Hospital, Copenhagen — E. Philipsen; Rigshospital, Copenhagen — M. Staun; Herlev Hospital, University of Copenhagen, Herlev — O.O. Thomsen; Germany: Charite–Campus Virchow Klinikum, Berlin — A. Dignass; University Rostock, Rostock — J. Emmrich; Reinhard-Nieter-Krankenhaus, Wilhelmshaven — P. Herzog; Rothenbaumchaussee 26, Hamburg — S. Howaldt; Universität Freiburg, Freiburg — W. Kreisel; Heekweg 15, Münster — T. Krummenerl; Universitätsklinikum Göttingen, Göttingen — G. Ramadori; Hospital of the University of Leipzig, Leipzig — I. Schiefke; Hospital for General Internal Medicine, Christian Albrechts University, Kiel — S. Schreiber; Hospital Essen-Nord, Essen — A. Stallmach; University of Ulm, Ulm — C. von Tirpitz; Hungary: Peterfy Teaching Hospital, Peterfy, Budapest — L. Bene; Pándy Kálmán Hospital, Gyula — Z. Gurzó; Veszprém County Csolnoky Ferenc Hospital, Veszprém — L. Lakatos; Petz Aladar County Teaching Hospital, Gyor — I. Rácz; St. Janos Hospital, Budapest — G. Székely; Szent Pantaleon Hospital, Dunaújváros — L. Varga Szabó; Semmelweis University, Budapest — T. Zágoni; Ireland: St James' University Hospital, Dublin — D. Kelleher; Beaumont Hospital, Dublin — F. Murray; St. Vincent's Hospital, Dublin — D. O'Donaghue; Israel: Tel Aviv Sourasky Medical Center, Tel Aviv — I. Dotan; Rambam Medical Center, Haifa — R. Elyakim; the Soroka University Medical Center, Beer Sheva — A. Fich; Rabin Medical Center, Petah Tikva — G.M. Fraser; Hadassah Medical Organization, Jerusalem — E. Goldin; Bnai-Zion Medical Center, Haifa — A. Lavy; Assaf Harofeh Medical Center, Beer Yaakov — E. Scapa; Lithuania: Kaunas Medical University Hospital, Kaunas — L. Kupcinskas; Public Institution Vilnius University Hospital, Vilnius — J. Valantinas; New Zealand: Christchurch Hospital, Christchurch — M. Barclay; Auckland Hospital, Auckland — M. Lane; Tauranga Hospital, Tauranga — D. Shaw; Shakespeare Specialist Group, Auckland — I. Wallace; Waikato Hospital, Hamilton — F. Weilert; Wellington Hospital, Wellington — J. Wyeth; Norway: Haugesund Hospital, Bedriftspostkontoret Haugesund — K. Bakkevold; University Hospital of Tromsø, Tromsø — J.R. Florholmen; Aker University Hospital, Oslo — J. Jahnsen; Ullevål University Hospital, Oslo — I. Lygren; Diakonhsemaets Hospital, Oslo — N. Stray; Sentralsjukehuset I Hedmark, Hamar — R. Torp; Regionsykehuset I Trondheim, Trondheim — Waldum HL; Poland: Centrum Leczenia Chorob, Warsaw — A. Bochenek; Nzoz Polimedica, Lodz — E. Czajkowska-Kaczmarek; Centrum Medyczne SOPMED Sopot, Sopot — M. Horynski; EuroMediCare Instytut Medyczny Wrocław, Wrocław — J. Leszczyszyn; Niepubliczny Zaklad Opieki Zdrowotnej VIVAMED, Warsaw — R. Petryka; 10 Szpital Wojskowy w Bydgoszczy, Warszawy 5, Bydgoszcz — J. Rudzinski; Wojewódzki Szpital Zespolony im. J. Śniadeckiego, Białystok — J. Sasiewicz; Serbia: Klinički Bolnički Centar Zvezdara, Belgrade — N. Jojic; Klinički Bolnički Centar Srbije, Belgrade — M. Krstic; Klinički Bolnički Centar Bezanijska Kosa, Belgrade — N. Milinic; Klinički Bolnički Centar Nis, Nis — A. Nagorni; Military Medical Academy, Belgrade — D. Tarabar; Singapore: National University Hospital — K.Y. Ho; Singapore General Hospital — C.J. Ooi; South Africa: Greenacres Hospital, Port Elizabeth — E. Fredericks; Linksfield Park Clinic, Johannesburg — L. Jackson; Johannesburg General Hospital, Johannesburg — K. Karlsson; Pretoria Academic Hospital, Pretoria — O. Mwantembe; Parklands Hospital, Durban — K.E. Pettengell; Medpark Building, Cape Town — S.J. Schmidt; Kloof Hospital, Pretoria — P.R. Spies, C.C.M. Ziady; Rosebank Clinic, Johannesburg — M. Strimling; New Groote Schuur Hospital, Cape Town — G.A.A. Watermeyer; Spain: Hospital Clinic de Barcelona, Barcelona — J. Panés Díaz; Ukraine: City Hospital No. 7, Dniepropetrovsk — N. Chukhriyenko; Lviv City Clinic No. 5, Konovaltsa Str 22 — R. Dutka; Crimean Medical University, Autonomous Republic of Crimea — I. Klyaritskaya; Odessa Clinical Regional Hospital, Odessa — E. Levchenko; City Clinical Hospital No. 6, Dniepropetrovsk — T. Pertseva; Hospital of the Security Service of Ukraine, Kiev — M.P. Zakharash; United States: Medical Associates Research Group, San Diego, CA — M. Bennett; Center for Medicine Research, Manchester, CT — J. Breiter; Rochester Institute for Digestive Diseases, Rochester, NY — W. Chey; Mountain West Gastroenterology, Salt Lake City — S. Desautels; Houston — A. Ertan; Wasatch Clinical Research, Salt Lake City — E.J. Eyring; Wisconsin Center for Advanced Research, Milwaukee — D.J. Geenen; Clinical Research Associates, Huntsville, AL — C.A. Goetsch; Harmony Clinical Research, Oro Valley, AZ — C.G. Gross; Comprehensive Clinical Research, Berlin, NJ — D.R. Hassman; the Vancouver Clinic, Vancouver, WA — V. Hee; Lynn Health Science Institute, Oklahoma City — J. Hogin; Piedmont Medical Research Associates, Winston-Salem, NC — R. Holmes; Gastroenterology United of Tulsa, Tulsa, OK — D. James; Medical Center for Clinical Research, San Diego, CA — W.D. Koltun; University of Washington Medical Center, Seattle — S.D. Lee; Advanced Research Institute, South Ogden, UT — J.E. Lowe; Targeted Research, Dayton, OH — D. Lutter; Gastroenterology and Hepatology Associates, Alexandria, VA — S. Malhotra; Carolina Research Center, Greenville, NC — S.P. Marcuard; Midwest Clinical Research Associates, Moline, IL — R. Movva; Charlottesville Medical Research, Charlottesville, VA — D.J. Pambianco; Bethany Medical Center, High Point, NC — L. Peters; Southeastern Indiana Gastroenterology, Columbus, IN — S.D. Pletcher; Tacoma Digestive Research Center, Tacoma, WA — W.M. Priebe; Torrance Clinical Research, Torrance, CA — M. Raikhel; New River Valley Research Institute, Christiansburg, VA — M. Ringold; Atlanta Gastroenterology Associates, Atlanta — B.A. Salzberg; Southern Clinical Research Consultants, Hollywood, FL — W. Schonfeld; Vanderbilt University Medical Center, Nashville — D. Schwartz; Lynn Institute of the Rockies, Colorado Springs, CO — A. Shafii; Penn State Milton S. Hershey Medical Center, Hershey, PA — J.P. Smith; Community Clinical Trials, Orange, CA — D. Stanton; Washington University School of Medicine, St. Louis — C. Stone; Jefferson City Medical Group, Jefferson City, MO — J. Wang; Clinical Research of West Florida, Clearwater, FL — L.M. Weiss.
- References
References
1
MacDonald TT ,Hutchings P ,Choy MY ,Murch S ,Cooke A . Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 1990;81:301-305
CrossRef | Web of Science | Medline2
Murch SH ,Lamkin VA ,Savage MO ,Walker-Smith JA ,MacDonald TT . Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 1991;32:913-917
CrossRef | Web of Science | Medline3
Braegger CP ,Nicholls S ,Murch SH ,Stephens S ,MacDonald TT . Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992;339:89-91
CrossRef | Web of Science | Medline4
Schreiber S ,Nikolaus S ,Hampe J , et al. Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease. Lancet 1999;353:459-461
CrossRef | Web of Science | Medline5
Targan SR ,Hanauer SB ,van Deventer SJ , et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. N Engl J Med 1997;337:1029-1035
Full Text | Web of Science | Medline6
Hanauer SB ,Feagan BG ,Lichtenstein GR , et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-1549
CrossRef | Web of Science | Medline7
Colombel JF ,Sandborn WJ ,Rutgeerts PJ , et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 2007;132:52-65
CrossRef | Web of Science | Medline8
Scallon BJ ,Moore MA ,Trinh H ,Knight DM ,Ghrayeb J . Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 1995;7:251-259
CrossRef | Web of Science | Medline9
van den Brande JMH ,Braat H ,van den Brink GR , et al. Infliximab but not etanercept induces apopotosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 2003;124:1774-1785
CrossRef | Web of Science | Medline10
Lugering A ,Schmidt M ,Lugering N ,Pauels HG ,Domschke W ,Kucharzik T . Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 2001;121:1145-1157
CrossRef | Web of Science | Medline11
Fossati G ,Nesbitt AM . Effect of the anti-TNF agents, adalimumab, etanercept, infliximab, and certolizumab PEGOL (CDP870) on the induction of apoptosis in activated peripheral blood lymphocytes and monocytes. Am J Gastroenterol 2005;100:Suppl:S298-S299
Web of Science12
Nesbitt AM ,Henry AJ . High affinity and potency of the pegylated FAB' fragment CDP870 -- a direct comparison with other anti-TNF agents. Am J Gastroenterol 2004;99:Suppl:S253-S253
Web of Science13
Fossati G ,Nesbitt A . In vitro complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by the anti-TNF agents adalimumab, etanercept, infliximab, and certolizumab pegol (CDP870). Am J Gastroenterol 2005;100:Suppl:S299-S299
CrossRef | Web of Science14
Schreiber S ,Rutgeerts P ,Fedorak RN , et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 2005;129:807-818[Erratum, Gastroenterology 2005;129:1808.]
CrossRef | Web of Science | Medline15
Sandborn WJ ,Feagan BG ,Stoinov S , et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med 2007;357:228-238
Full Text | Web of Science | Medline16
Best WR ,Becktel JM ,Singleton JW ,Kern F Jr . Development of a Crohn's disease activity index: National Cooperative Crohn's Disease Study. Gastroenterology 1976;70:439-444
Web of Science | Medline17
Choy EH ,Hazleman B ,Smith M , et al. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology (Oxford) 2002;41:1133-1137
CrossRef | Web of Science | Medline18
Irvine EJ ,Feagan B ,Rochon J , et al. Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Gastroenterology 1994;106:287-296
Web of Science | Medline19
Koch GG ,Gansky SA . Statistical considerations for multiplicity in confirmatory protocols. Drug Inf J 1996;30:523-534
CrossRef20
Tan EM ,Feltkamp TE ,Smolen JS , et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997;40:1601-1611
CrossRef | Web of Science | Medline21
Winter TA ,Wright J ,Ghosh S ,Jahnsen J ,Innes A ,Round P . Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to-severe Crohn's disease: an exploratory study. Aliment Pharmacol Ther 2004;20:1337-1346
CrossRef | Web of Science | Medline22
Keystone E ,Choy EH ,Kalden J ,Klareskog L ,Sany J ,Smolen J . CDP870, a novel, PEGylated, humanized TNF-alpha inhibitor, is effective in treating the signs and symptoms of rheumatoid arthritis (RA). Arthritis Rheum 2001;44:2946-2946
Web of Science
- Citing Articles (216)
Citing Articles
1
Pal Miheller, Lajos Sandor Kiss, Katalin Lorinczy, Peter Laszlo Lakatos. (2012) Anti-TNF trough levels and detection of antibodies to anti-TNF in inflammatory bowel disease: are they ready for everyday clinical use?. Expert Opinion on Biological Therapy 12:2, 179-192
CrossRef2
Jean-Frédéric Colombel, Brian G. Feagan, William J. Sandborn, Gert Van Assche, Anne M. Robinson. (2012) Therapeutic drug monitoring of biologics for inflammatory bowel disease. Inflammatory Bowel Diseases 18:2, 349-358
CrossRef3
Katalin Lőrinczy, Pál Miheller, Sándor Lajos Kiss, Péter László Lakatos. (2012) A biológiai kezelés során bekövetkező hatásvesztés gyakorisága, okai és klinikai megközelítése gyulladásos bélbetegségek esetén. Orvosi Hetilap 153:5, 163-173
CrossRef4
Cem Kayhan, Bosny Pierre-Louis, David Sen, Mylene Serna. (2012) Efficacy of Certolizumab Pegol in Crohn's Disease: Response to Ford et al.. The American Journal of Gastroenterology 107:2, 321-321
CrossRef5
Tian-Lu Cheng, Kuo-Hsiang Chuang, Bing-Mae Chen, Steve R Roffler. (2012) Analytical measurement of PEGylated molecules. Bioconjugate Chemistry120115104848009
CrossRef6
Edouard Louis, Jean–Yves Mary, Gwenola Vernier–Massouille, Jean–Charles Grimaud, Yoram Bouhnik, David Laharie, Jean–Louis Dupas, Hélène Pillant, Laurence Picon, Michel Veyrac, Mathurin Flamant, Guillaume Savoye, Raymond Jian, Martine DeVos, Raphaël Porcher, Gilles Paintaud, Eric Piver, Jean–Frédéric Colombel, Marc Lemann. (2012) Maintenance of Remission Among Patients With Crohn's Disease on Antimetabolite Therapy After Infliximab Therapy Is Stopped. Gastroenterology 142:1, 63-70.e5
CrossRef7
Robert Löfberg, Edouard V. Louis, Walter Reinisch, Anne M. Robinson, Martina Kron, Anne Camez, Paul F. Pollack. (2012) Adalimumab produces clinical remission and reduces extraintestinal manifestations in Crohn's disease: Results from CARE. Inflammatory Bowel Diseases 18:1, 1-9
CrossRef8
Brian G. Feagan, Marc Lémann, Ragnar Befrits, William Connell, Geert D'Haens, Subrata Ghosh, Pierre Michetti, Thomas Ochsenkühn, Remo Panaccione, Stefan Schreiber, Mark Silverberg, Dario Sorrentino, C. Janneke van der Woude, Severine Vermeire, Paul Rutgeerts. (2012) Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: An expert consensus report. Inflammatory Bowel Diseases 18:1, 152-160
CrossRef9
G. Cullen, D. Kroshinsky, A. S. Cheifetz, J. R. Korzenik. (2011) Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature. Alimentary Pharmacology & Therapeutics 34:11-12, 1318-1327
CrossRef10
Mario Cottone, Sara Renna, Ambrogio Orlando, Filippo Mocciaro. (2011) Medical management of Crohn's disease. Expert Opinion on Pharmacotherapy 12:16, 2505-2525
CrossRef11
Sharmeel K Wasan, Sunanda V Kane. (2011) Adalimumab for the treatment of inflammatory bowel disease. Expert Review of Gastroenterology & Hepatology 5:6, 679-684
CrossRef12
Michael A. Kamm, Siew C. Ng, Peter De Cruz, Patrick Allen, Stephen B. Hanauer. (2011) Practical application of anti-TNF therapy for luminal Crohn's disease. Inflammatory Bowel Diseases 17:11, 2366-2391
CrossRef13
Alexander C Ford, Nicholas J Talley, Paul Moayyedi. (2011) Response to Atreja et al.. The American Journal of Gastroenterology 106:11, 2046-2046
CrossRef14
William J. Sandborn, Gert van Assche, Walter Reinisch, Jean–Frederic Colombel, Geert D'Haens, Douglas C. Wolf, Martina Kron, Mary Beth Tighe, Andreas Lazar, Roopal B. Thakkar. (2011) Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative Colitis. Gastroenterology
CrossRef15
Andrés Sansó Sureda, Vicenç Rocamora Durán, Amparo Sapiña Camaró, Vanesa Royo Escosa, María José Bosque López. (2011) Ustekinumab en paciente con enfermedad de Crohn y psoriasis inducida por anti-TNF-α. Gastroenterología y Hepatología 34:8, 546-550
CrossRef16
Glen A. Doherty, Adam S. Cheifetz. 2011. One Drug or Two: Do Patients on Biologics Need Concurrent Immunomodulation?. , 113-116.
CrossRef17
Jennifer L. Jones. 2011. Are all Anti-TNF Agents the Same?. , 107-112.
CrossRef18
David T. Rubin. 2011. What can we do with Crohn's Patients who Fail or Lose Response to Anti-TNF Therapy?. , 124-128.
CrossRef19
Ashwin N. Ananthakrishnan, Chin Hur, Joshua R. Korzenik. (2011) Certolizumab Pegol Compared to Natalizumab in Patients with Moderate to Severe Crohn’s Disease: Results of a Decision Analysis. Digestive Diseases and Sciences
CrossRef20
David T. Rubin, Remo Panaccione, Jingdong Chao, Anne M. Robinson. (2011) A practical, evidence-based guide to the use of adalimumab in Crohn’s disease. Current Medical Research and Opinion 27:9, 1803-1813
CrossRef21
Gert Van Assche, James D Lewis, Gary R Lichtenstein, Edward V Loftus, Qin Ouyang, Julian Panes, Corey A Siegel, William J Sandborn, Simon P L Travis, Jean-Frederic Colombel. (2011) The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organisation: Safety. The American Journal of Gastroenterology 106:9, 1594-1602
CrossRef22
William J. Sandborn, Stefan Schreiber, Brian G. Feagan, Paul Rutgeerts, Ziad H. Younes, Ralph Bloomfield, Geoffroy Coteur, Juan Pablo Guzman, Geert R. D'Haens. (2011) Certolizumab Pegol for Active Crohn's Disease: A Placebo-Controlled, Randomized Trial. Clinical Gastroenterology and Hepatology 9:8, 670-678.e3
CrossRef23
M. A. Kamm, S. B. Hanauer, R. Panaccione, J.-F. Colombel, W. J. Sandborn, P. F. Pollack, Q. Zhou, A. M. Robinson. (2011) Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn’s disease. Alimentary Pharmacology & Therapeutics 34:3, 306-317
CrossRef24
Meenu Wadhwa, Robin Thorpe. 2011. Guidance on Immunogenicity Assessment of Biologically Derived Therapeutic Proteins: A European Perspective. , 37-56.
CrossRef25
S. Danese, G. Fiorino, W. Reinisch. (2011) Review article: causative factors and the clinical management of patients with Crohn’s disease who lose response to anti-TNF-α therapy. Alimentary Pharmacology & Therapeutics 34:1, 1-10
CrossRef26
Stephan R. Vavricka, Alain M. Schoepfer, Georg Bansky, Janek Binek, Christian Felley, Martin Geyer, Michael Manz, Gerhard Rogler, Philippe de Saussure, Bernhard Sauter, Michael Scharl, Frank Seibold, Alex Straumann, Pierre Michetti, . (2011) Efficacy and safety of certolizumab pegol in an unselected crohn's disease population: 26-week data of the FACTS II survey. Inflammatory Bowel Diseases 17:7, 1530-1539
CrossRef27
O. H. Nielsen, J. B. Seidelin, L. K. Munck, G. Rogler. (2011) Use of biological molecules in the treatment of inflammatory bowel disease. Journal of Internal Medicine 270:1, 15-28
CrossRef28
I. Wakefield, S. Stephens, R. Foulkes, A. Nesbitt, T. Bourne. (2011) The Use of Surrogate Antibodies to Evaluate the Developmental and Reproductive Toxicity Potential of an Anti-TNF PEGylated Fab' Monoclonal Antibody. Toxicological Sciences 122:1, 170-176
CrossRef29
Dustin G. James, Da Hea Seo, Jiajing Chen, Caroline Vemulapalli, Christian D. Stone. (2011) Efalizumab, a Human Monoclonal Anti-CD11a Antibody, in the Treatment of Moderate to Severe Crohn’s Disease: An Open-Label Pilot Study. Digestive Diseases and Sciences 56:6, 1806-1810
CrossRef30
Heidi Waters, Julie Vanderpoel, Scott McKenzie, Orsolya Lunacsek, Meg Franklin, Barbara Lennert, John Goff, Damian H. Augustyn. (2011) Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review. Journal of Medical Economics397-402
CrossRef31
Michael V. Chiorean, Bhupesh Pokhrel, Jaya Adabala, Debra J. Helper, Cynthia S. Johnson, Beth Juliar. (2011) Incidence and Risk Factors for Lymphoma in a Single-Center Inflammatory Bowel Disease Population. Digestive Diseases and Sciences 56:5, 1489-1495
CrossRef32
S. Ben-Horin, Y. Chowers. (2011) Review article: loss of response to anti-TNF treatments in Crohn’s disease. Alimentary Pharmacology & Therapeutics 33:9, 987-995
CrossRef33
B. G. Feagan, S. B. Hanauer, G. Coteur, S. Schreiber. (2011) Evaluation of a daily practice composite score for the assessment of Crohn’s disease: the treatment impact of certolizumab pegol. Alimentary Pharmacology & Therapeutics 33:10, 1143-1151
CrossRef34
Eduardo J. Villablanca, Barbara Cassani, Ulrich H. von Andrian, J. Rodrigo Mora. (2011) Blocking Lymphocyte Localization to the Gastrointestinal Mucosa as a Therapeutic Strategy for Inflammatory Bowel Diseases. Gastroenterology 140:6, 1776-1784.e5
CrossRef35
Smriti Raychaudhuri. 2011. Biologics. , 147-163.
CrossRef36
Alexander C Ford, William J Sandborn, Khurram J Khan, Stephen B Hanauer, Nicholas J Talley, Paul Moayyedi. (2011) Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. The American Journal of Gastroenterology 106:4, 644-659
CrossRef37
Henit Yanai, Stephen B Hanauer. (2011) Assessing Response and Loss of Response to Biological Therapies in IBD. The American Journal of Gastroenterology 106:4, 685-698
CrossRef38
Arthur F. Kavanaugh, Lloyd F. Mayer, John J. Cush, Stephen B. Hanauer. (2011) Shared Experiences and Best Practices in the Management of Rheumatoid Arthritis and Crohn's Disease. The American Journal of Medicine 124:4, e1-e18
CrossRef39
Nicholas J Talley, Maria T Abreu, Jean-Paul Achkar, Charles N Bernstein, Marla C Dubinsky, Stephen B Hanauer, Sunanda V Kane, William J Sandborn, Thomas A Ullman, Paul Moayyedi. (2011) An Evidence-Based Systematic Review on Medical Therapies for Inflammatory Bowel Disease. The American Journal of Gastroenterology 106, S2-S25
CrossRef40
B. G. Feagan, W. J. Sandborn, D. C. Wolf, G. Coteur, O. Purcaru, Y. Brabant, P. J. Rutgeerts. (2011) Randomised clinical trial: improvement in health outcomes with certolizumab pegol in patients with active Crohn’s disease with prior loss of response to infliximab. Alimentary Pharmacology & Therapeutics 33:5, 541-550
CrossRef41
Ian C Lawrance. (2011) Certolizumab pegol in the treatment of Crohn’s disease: evidence from the PRECiSE clinical trial program. Clinical Investigation 1:3, 459-465
CrossRef42
Jasvinder A Singh, George A Wells, Robin Christensen, Elizabeth Tanjong Ghogomu, Lara Maxwell, John K MacDonald, Graziella Filippini, Nicole Skoetz, Damian Francis, Luciane C Lopes, Gordon H Guyatt, Jochen Schmitt, Loredana La Mantia, Tobias Weberschock, Juliana F Roos, Hendrik Siebert, Sarah Hershan, Michael PT Lunn, Peter Tugwell, Rachelle Buchbinder, Jasvinder A Singh. 2011. Adverse effects of biologics: a network meta-analysis and Cochrane overview. .
CrossRef43
Vicente Ruiz Garcia, Paresh Jobanputra, Amanda Burls, Juan B Cabello, José G Gálvez Muñoz, Encarnación SC Saiz Cuenca, Anne Fry-Smith, Vicente Ruiz Garcia. 2011. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. .
CrossRef44
Ashwin N. Ananthakrishnan, Emily L. McGinley, David G. Binion, Kia Saeian. (2011) A Nationwide Analysis of Changes in Severity and Outcomes of Inflammatory Bowel Disease Hospitalizations. Journal of Gastrointestinal Surgery 15:2, 267-276
CrossRef45
Geert R D'Haens, Remo Panaccione, Peter D R Higgins, Severine Vermeire, Miquel Gassull, Yehuda Chowers, Stephen B Hanauer, Hans Herfarth, Daan W Hommes, Michael Kamm, Robert Löfberg, A Quary, Bruce Sands, A Sood, G Watermayer, Bret Lashner, Marc Lémann, Scott Plevy, Walter Reinisch, Stefan Schreiber, Corey Siegel, Stephen Targan, M Watanabe, Brian Feagan, William J Sandborn, Jean Frédéric Colombel, Simon Travis. (2011) The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response?. The American Journal of Gastroenterology 106:2, 199-212
CrossRef46
Sophia Koo, Francisco M. Marty, Lindsey R. Baden. (2011) Infectious Complications Associated with Immunomodulating Biologic Agents. Hematology/Oncology Clinics of North America 25:1, 117-138
CrossRef47
Vincent Billioud, David Laharie, Jérôme Filippi, Xavier Roblin, Abderrahim Oussalah, Jean-Baptiste Chevaux, Xavier Hébuterne, Marc-André Bigard, Laurent Peyrin-Biroulet. (2011) Adherence to adalimumab therapy in Crohn's disease: A French multicenter experience. Inflammatory Bowel Diseases 17:1, 152-159
CrossRef48
Stephan R. Vavricka, Nicoletta Bentele, Michael Scharl, Gerhard Rogler, Jonas Zeitz, Pascal Frei, Alex Straumann, Janek Binek, Alain M. Schoepfer, Michael Fried, . (2011) Systematic assessment of factors influencing preferences of crohn's disease patients in selecting an anti-tumor necrosis factor agent (CHOOSE TNF TRIAL). Inflammatory Bowel Diseasesn/a-n/a
CrossRef49
Oliver Gouldthorpe, Anthony G. Catto-Smith, George Alex. (2011) Biologics in Paediatric Crohn's Disease. Gastroenterology Research and Practice 2011, 1-10
CrossRef50
Filomena Morisco, Fabiana Castiglione, Antonio Rispo, Tommaso Stroffolini, Roberto Vitale, Stefano Sansone, Rocco Granata, Ambrogio Orlando, Riccardo Marmo, Gabriele Riegler, Maurizio Vecchi, Livia Biancone, Nicola Caporaso. (2011) Hepatitis B virus infection and immunosuppressive therapy in patients with inflammatory bowel disease. Digestive and Liver Disease 43, S40-S48
CrossRef51
Charlotte I. de Bie, Johanna C. Escher, Lissy de Ridder. (2011) Antitumor necrosis factor treatment for pediatric inflammatory bowel disease. Inflammatory Bowel Diseasesn/a-n/a
CrossRef52
Byung Ik Jang. (2011) Is Certolizumab Pegol an Effective Longterm Maintenance Treatment for Moderate to Severe Crohn's Disease?. The Korean Journal of Gastroenterology 58:2, 121
CrossRef53
David T. Rubin, Parvez Mulani, Jingdong Chao, Paul F. Pollack, Arielle G. Bensimon, Andrew P. Yu, Subrata Ghosh. (2011) Effect of adalimumab on clinical laboratory parameters in patients with Crohn's disease: Results from the CHARM trial. Inflammatory Bowel Diseasesn/a-n/a
CrossRef54
Lajos Sandor Kiss, Maria Papp, Barbara Dorottya Lovasz, Zsuzsanna Vegh, Petra Anna Golovics, Eszter Janka, Eva Varga, Miklos Szathmari, Peter Laszlo Lakatos. (2011) High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: A marker for patient classification?. Inflammatory Bowel Diseasesn/a-n/a
CrossRef55
Sreedhar Subramanian, Vijay Yajnik, Bruce E. Sands, Garret Cullen, Joshua R. Korzenik. (2011) Characterization of patients with infliximab-induced lupus erythematosus and outcomes after retreatment with a second anti-TNF agent. Inflammatory Bowel Diseases 17:1, 99-104
CrossRef56
Shervin Rabizadeh, Jeffrey Hyams, Marla Dubinsky. 2011. Crohn’s Disease. , 472-489.
CrossRef57
Filippo Mocciaro, Ambrogio Orlando, Sara Renna, Maria Rosa Rizzuto, Mario Cottone. (2011) Oral lichen planus after certolizumab pegol treatment in a patient with Crohn's disease. Journal of Crohn s and Colitis 5:2, 173
CrossRef58
S. Schreiber, I. C. Lawrance, O. Ø. Thomsen, S. B. Hanauer, R. Bloomfield, W. J. Sandborn. (2011) Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease - subgroup results from a placebo-controlled study. Alimentary Pharmacology & Therapeutics 33:2, 185-193
CrossRef59
Steevens N. S. Alconcel, Arnold S. Baas, Heather D. Maynard. (2011) FDA-approved poly(ethylene glycol)–protein conjugate drugs. Polymer Chemistry 2:7, 1442
CrossRef60
Ambrogio Orlando, Sara Renna, Filippo Mocciaro, Maria Cappello, Roberto Di Mitri, Claudia Randazzo, Mario Cottone. (2011) Adalimumab in steroid-dependent Crohn's disease patients: Prognostic factors for clinical benefit. Inflammatory Bowel Diseasesn/a-n/a
CrossRef61
William J. Sandborn, Jean-Frédéric Colombel, Stefan Schreiber, Scott E. Plevy, Paul F. Pollack, Anne M. Robinson, Jingdong Chao, Parvez Mulani. (2011) Dosage adjustment during long-term adalimumab treatment for Crohn's disease: Clinical efficacy and pharmacoeconomics. Inflammatory Bowel Diseases 17:1, 141-151
CrossRef62
Norman T. Ilowite, Ronald M. Laxer. 2011. PHARMACOLOGY AND DRUG THERAPY. , 71-126.
CrossRef63
R. K. Burt, R. M. Craig, F. Milanetti, K. Quigley, P. Gozdziak, J. Bucha, A. Testori, A. Halverson, L. Verda, W. J. S. de Villiers, B. Jovanovic, Y. Oyama. (2010) Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up. Blood 116:26, 6123-6132
CrossRef64
Brendan Boyle, Laura Mackner, Christina Ross, Jonathan Moses, Soma Kumar, Wallace Crandall. (2010) A Single-center Experience With Methotrexate After Thiopurine Therapy in Pediatric Crohn Disease. Journal of Pediatric Gastroenterology and Nutrition 51:6, 714-717
CrossRef65
Jean–François Rahier, Sébastien Buche, Laurent Peyrin–Biroulet, Yoram Bouhnik, Bernard Duclos, Edouard Louis, Pavol Papay, Matthieu Allez, Jacques Cosnes, Antoine Cortot, David Laharie, Jean–Marie Reimund, Marc Lémann, Emmanuel Delaporte, Jean–Frédéric Colombel. (2010) Severe Skin Lesions Cause Patients With Inflammatory Bowel Disease to Discontinue Anti–Tumor Necrosis Factor Therapy. Clinical Gastroenterology and Hepatology 8:12, 1048-1055
CrossRef66
Fernando Magro, Francisco Portela. (2010) Management of Inflammatory Bowel Disease with Infliximab and Other Anti-Tumor Necrosis Factor Alpha Therapies. BioDrugs 24, 3-14
CrossRef67
Stephen B. Hanauer, Asher A. Kornbluth, Julie Messick, David T. Rubin, William J. Sandborn, Bruce E. Sands. (2010) Clinical scenarios in IBD: Optimizing the use of conventional and biologic agents. Inflammatory Bowel Diseases 16:S1, S1-S11
CrossRef68
Sara Renna, Ambrogio Orlando, Gaspare Solina, Mario Cottone. (2010) Combined treatment with adalimumab and surgery in a patient with steroid-dependent Crohn's disease complicated by perianal disease. Digestive and Liver Disease Supplements 4:1, 34-37
CrossRef69
C. Janneke van der Woude, Pieter Stokkers, Ad A. van Bodegraven, Gert Van Assche, Zbigniew Hebzda, Leszek Paradowski, Geert D'Haens, Subrata Ghosh, Brian Feagan, Paul Rutgeerts, Gerard Dijkstra, Dirk J. de Jong, Bas Oldenburg, Mahdi Farhan, Tristan Richard, Yann Dean, Daniel W. Hommes. (2010) Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of NI-0401 (a fully human anti-CD3 monoclonal antibody) in patients with moderate to severe active Crohn's disease. Inflammatory Bowel Diseases 16:10, 1708-1716
CrossRef70
Matthieu Allez, Konstantinos Karmiris, Edouard Louis, Gert Van Assche, Shomron Ben-Horin, Amir Klein, Janneke Van der Woude, Filip Baert, Rami Eliakim, Konstantinos Katsanos, Jørn Brynskov, Flavio Steinwurz, Silvio Danese, Severine Vermeire, Jean-Luc Teillaud, Marc Lémann, Yehuda Chowers. (2010) Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: Definitions, frequency and pharmacological aspects. Journal of Crohn's and Colitis 4:4, 355-366
CrossRef71
Faten N. Aberra, Gary R. Lichtenstein. 2010. Crohn Disease. , 225-235.
CrossRef72
Brian G Feagan, John WD McDonald. 2010. Crohn's Disease. , 211-231.
CrossRef73
Thomas W. Lee, Richard N. Fedorak. (2010) Tumor Necrosis Factor-α Monoclonal Antibodies in the Treatment of Inflammatory Bowel Disease: Clinical Practice Pharmacology. Gastroenterology Clinics of North America 39:3, 543-557
CrossRef74
&NA;. (2010) Tumour necrosis factor (TNF) inhibitors are an effective option in the management of Crohnʼs disease. Drugs & Therapy Perspectives 26:9, 15-18
CrossRef75
Gil Y. Melmed, Brennan M. Spiegel, Brian Bressler, Adam S. Cheifetz, Shane M. Devlin, Laura E. Harrell, Peter M. Irving, Jennifer Jones, Gilaad G. Kaplan, Patricia L. Kozuch, Fernando S. Velayos, Leonard Baidoo, Miles P. Sparrow, Corey A. Siegel. (2010) The Appropriateness of Concomitant Immunomodulators With Anti–Tumor Necrosis Factor Agents for Crohn's Disease: One Size Does Not Fit All. Clinical Gastroenterology and Hepatology 8:8, 655-659
CrossRef76
William J. Sandborn, Maria T. Abreu, Geert D'Haens, Jean–Frédéric Colombel, Severine Vermeire, Krassimir Mitchev, Corinne Jamoul, Richard N. Fedorak, Martina E. Spehlmann, Douglas C. Wolf, Scott Lee, Paul Rutgeerts. (2010) Certolizumab Pegol in Patients With Moderate to Severe Crohn's Disease and Secondary Failure to Infliximab. Clinical Gastroenterology and Hepatology 8:8, 688-695.e2
CrossRef77
S. B. Hanauer, J. Panes, J.-F. Colombel, R. Bloomfield, S. Schreiber, W. J. Sandborn. (2010) Clinical trial: impact of prior infliximab therapy on the clinical response to certolizumab pegol maintenance therapy for Crohn’s disease. Alimentary Pharmacology & Therapeutics 32:3, 384-393
CrossRef78
Anna Bellizzi, Valentina Barucca, Daniela Fioriti, Maria T. Colosimo, Monica Mischitelli, Elena Anzivino, Fernanda Chiarini, Valeria Pietropaolo. (2010) Early years of biological agents therapy in Crohn's disease and risk of the human polyomavirus JC reactivation. Journal of Cellular Physiology 224:2, 316-326
CrossRef79
William J. Sandborn, Stefan Schreiber, Stephen B. Hanauer, Jean–Frédéric Colombel, Ralph Bloomfield, Gary R. Lichtenstein. (2010) Reinduction With Certolizumab Pegol in Patients With Relapsed Crohn's Disease: Results From the PRECiSE 4 Study. Clinical Gastroenterology and Hepatology 8:8, 696-702.e1
CrossRef80
Athos Bousvaros. (2010) Use of immunomodulators and biologic therapies in children with inflammatory bowel disease. Expert Review of Clinical Immunology 6:4, 659-666
CrossRef81
Gary R. Lichtenstein, Ole Ø. Thomsen, Stefan Schreiber, Ian C. Lawrance, Stephen B. Hanauer, Ralph Bloomfield, William J. Sandborn. (2010) Continuous Therapy With Certolizumab Pegol Maintains Remission of Patients With Crohn's Disease for up to 18 Months. Clinical Gastroenterology and Hepatology 8:7, 600-609
CrossRef82
Brijen Shah, Lloyd Mayer. (2010) Current status of monoclonal antibody therapy for the treatment of inflammatory bowel disease. Expert Review of Clinical Immunology 6:4, 607-620
CrossRef83
Gargi Shikhare, Subra Kugathasan. (2010) Inflammatory bowel disease in children: current trends. Journal of Gastroenterology 45:7, 673-682
CrossRef84
Meenakshi Bewtra, James D Lewis. (2010) Update on the risk of lymphoma following immunosuppressive therapy for inflammatory bowel disease. Expert Review of Clinical Immunology 6:4, 621-631
CrossRef85
Charles N. Bernstein. (2010) Anti–Tumor Necrosis Factor Therapy in Crohn's Disease: More Information and More Questions About the Long Term. Clinical Gastroenterology and Hepatology 8:7, 556-558
CrossRef86
Michael F. Cunningham, Neil G. Docherty, J. Calvin Coffey, John P. Burke, P. Ronan O’Connell. (2010) Postsurgical Recurrence of Ileal Crohn’s Disease: An Update on Risk Factors and Intervention Points to a Central Role for Impaired Host-Microflora Homeostasis. World Journal of Surgery 34:7, 1615-1626
CrossRef87
Stefan Schreiber, Jean-Frédéric Colombel, Ralph Bloomfield, Susanna Nikolaus, Jürgen Schölmerich, Julian Panés, William J Sandborn. (2010) Increased Response and Remission Rates in Short-Duration Crohn's Disease With Subcutaneous Certolizumab Pegol: An Analysis of PRECiSE 2 Randomized Maintenance Trial Data. The American Journal of Gastroenterology 105:7, 1574-1582
CrossRef88
Ashwin N Ananthakrishnan, David G Binion. (2010) Editorial: Improved Efficacy of Biological Maintenance Therapy in “Early” Compared With “Late” Crohn's Disease: Strike While the Iron Is Hot With Anti-TNF Agents?. The American Journal of Gastroenterology 105:7, 1583-1585
CrossRef89
Veruscka Leso, Lorenzo Leggio, Alessandro Armuzzi, Giovanni Gasbarrini, Antonio Gasbarrini, Giovanni Addolorato. (2010) Role of the tumor necrosis factor antagonists in the treatment of inflammatory bowel disease: an update. European Journal of Gastroenterology & Hepatology 22:7, 779-786
CrossRef90
Yago González-Lama, María Isabel Vera, Marta Calvo, Lluís Abreu. (2010) Marcadores de evolución de la enfermedad inflamatoria intestinal tratada con inmunomoduladores o agentes biológicos. Gastroenterología y Hepatología 33:6, 449-460
CrossRef91
Inès Zidi, Souhir Mestiri, Aghleb Bartegi, Nidhal Ben Amor. (2010) TNF-α and its inhibitors in cancer. Medical Oncology 27:2, 185-198
CrossRef92
Sophia Koo, Francisco M. Marty, Lindsey R. Baden. (2010) Infectious Complications Associated with Immunomodulating Biologic Agents. Infectious Disease Clinics of North America 24:2, 285-306
CrossRef93
R. PANACCIONE, J.-F. COLOMBEL, W. J. SANDBORN, P. RUTGEERTS, G. R. D’HAENS, A. M. ROBINSON, J. CHAO, P. M. MULANI, P. F. POLLACK. (2010) Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn’s disease. Alimentary Pharmacology & Therapeutics 31:12, 1296-1309
CrossRef94
B. G. FEAGAN, M. C. REILLY, L. GERLIER, Y. BRABANT, M. BROWN, S. SCHREIBER. (2010) Clinical trial: the effects of certolizumab pegol therapy on work productivity in patients with moderate-to-severe Crohn’s disease in the PRECiSE 2 study. Alimentary Pharmacology & Therapeutics 31:12, 1276-1285
CrossRef95
Meenu Wadhwa, Robin Thorpe. (2010) Unwanted immunogenicity: lessons learned and future challenges. Bioanalysis 2:6, 1073-1084
CrossRef96
Andrew C. Chan, Paul J. Carter. (2010) Therapeutic antibodies for autoimmunity and inflammation. Nature Reviews Immunology 10:5, 301-316
CrossRef97
Waqqas Afif, Edward V Loftus, William A Faubion, Sunanda V Kane, David H Bruining, Karen A Hanson, William J Sandborn. (2010) Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Concentrations in Patients With Inflammatory Bowel Disease. The American Journal of Gastroenterology 105:5, 1133-1139
CrossRef98
Javier P. Gisbert. (2010) Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding. Inflammatory Bowel Diseases 16:5, 881-895
CrossRef99
Geert D'Haens. (2010) Editorial: Anti-TNF Treatment in Crohn's Disease: Toward Tailored Therapy?. The American Journal of Gastroenterology 105:5, 1140-1141
CrossRef100
F. Grimpen, P. Pavli. (2010) Advances in the management of inflammatory bowel disease. Internal Medicine Journal 40:4, 258-264
CrossRef101
Severine Vermeire, Stefan Schreiber, William J. Sandborn, Cécile Dubois, Paul Rutgeerts. (2010) Correlation Between the Crohn's Disease Activity and Harvey–Bradshaw Indices in Assessing Crohn's Disease Severity. Clinical Gastroenterology and Hepatology 8:4, 357-363
CrossRef102
Ming Valerie Lin, Wojciech Blonski, Gary R Lichtenstein. (2010) What is the optimal therapy for Crohn’s disease: step-up or top-down?. Expert Review of Gastroenterology & Hepatology 4:2, 167-180
CrossRef103
Jonas Zeitz, Milo Huber, Gerhard Rogler. (2010) Schwerer Verlauf einer Miliartuberkulose bei einem 34-jährigen Patienten mit Colitis ulcerosa und HIV-Infektion unter einer TNF-α-Antikörper-Therapie. Medizinische Klinik 105:4, 314-318
CrossRef104
Nazila Assasi, Gord Blackhouse, Feng Xie, John K Marshall, E Jan Irvine, Kathryn Gaebel, Diana Robertson, Kaitryn Campbell, Rob Hopkins, Ron Goeree. (2010) Patient outcomes after anti TNF-α drugs for Crohn’s disease. Expert Review of Pharmacoeconomics & Outcomes Research 10:2, 163-175
CrossRef105
W. Connell, J. M. Andrews, S. Brown, M. Sparrow. (2010) Practical guidelines for treating inflammatory bowel disease safely with anti-tumour necrosis factor therapy in Australia. Internal Medicine Journal 40:2, 139-149
CrossRef106
Nilanjan Ghosh, Rituparna Chaki, Vivekananda Mandal, G. David Lin, Subhash C. Mandal. (2010) Mechanisms and Efficacy of Immunobiologic Therapies for Inflammatory Bowel Diseases. International Reviews of Immunology 29:1, 4-37
CrossRef107
Shanika de Silva, Shane Devlin, Remo Panaccione. (2010) Optimizing the safety of biologic therapy for IBD. Nature Reviews Gastroenterology & Hepatology 7:2, 93-101
CrossRef108
Meenakshi Bewtra, James D. Lewis. (2010) Safety Profile of IBD: Lymphoma Risks. Medical Clinics of North America 94:1, 93-113
CrossRef109
Gert Van Assche, Axel Dignass, Walter Reinisch, C. Janneke van der Woude, Andreas Sturm, Martine De Vos, Mario Guslandi, Bas Oldenburg, Iris Dotan, Philippe Marteau. (2010) The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. Journal of Crohn s and Colitis 4:1, 63
CrossRef110
Fernando Gomollón, Javier P. Gisbert. (2010) ¿Es necesario asociar inmunomoduladores al tratamiento biológico en la enfermedad inflamatoria intestinal?. Gastroenterología y Hepatología 33:1, 43-53
CrossRef111
M. ALLEZ, S. VERMEIRE, N. MOZZICONACCI, P. MICHETTI, D. LAHARIE, E. LOUIS, M.-A. BIGARD, X. HÃBUTERNE, X. TRETON, A. KOHN, P. MARTEAU, A. CORTOT, C. NICHITA, G. VAN ASSCHE, P. RUTGEERTS, M. LÃMANN, J.-F. COLOMBEL. (2010) The efficacy and safety of a third anti-TNF monoclonal antibody in Crohnâs disease after failure of two other anti-TNF antibodies. Alimentary Pharmacology & Therapeutics 31:1, 92-101
CrossRef112
Jennifer Leong, Blanche Fung-Liu. (2010) A Case Report of Nephrotic Syndrome Due to Intake of Certolizumab Pegol in a Patient With Crohn's Disease. The American Journal of Gastroenterology 105:1, 234-234
CrossRef113
Shane M. Devlin, Remo Panaccione. (2010) Evolving Inflammatory Bowel Disease Treatment Paradigms: Top-Down Versus Step-Up. Medical Clinics of North America 94:1, 1-18
CrossRef114
Bret A. Lashner, Aaron Brzezinski. 2010. Crohn's Disease. , 297-303.
CrossRef115
Maria Josefina Etchevers, Ingrid Ordás, Elena Ricart. (2010) Optimizing the Use of Tumour Necrosis Factor Inhibitors in Crohnʼs Disease. Drugs 70:2, 109-120
CrossRef116
A. Dignass, G. Van Assche, J.O. Lindsay, M. Lémann, J. Söderholm, J.F. Colombel, S. Danese, A. D'Hoore, M. Gassull, F. Gomollón. (2010) The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management. Journal of Crohn s and Colitis 4:1, 28
CrossRef117
Shane M. Devlin, Remo Panaccione. (2009) Evolving Inflammatory Bowel Disease Treatment Paradigms: Top-Down Versus Step-Up. Gastroenterology Clinics of North America 38:4, 577-594
CrossRef118
Jason E. Gonzaga, Ashwin N. Ananthakrishnan, Mazen Issa, Dawn B. Beaulieu, Sue Skaros, Yelena Zadvornova, Kathryn Johnson, Mary F. Otterson, David G. Binion. (2009) Durability of infliximab in Crohn's disease: A single-center experience. Inflammatory Bowel Diseases 15:12, 1837-1843
CrossRef119
Marc Ferrante, Geert D’Haens, Paul Rutgeerts, Séverine Vermeire, Gert Assche. (2009) Optimizing biologic therapies for inflammatory bowel disease (ulcerative colitis and crohn’s disease). Current Gastroenterology Reports 11:6, 504-508
CrossRef120
Pascal Juillerat, John-Paul Vader, Christian Felley, Valérie Pittet, Jean-Jacques Gonvers, Christian Mottet, Willem A. Bemelman, Marc Lémann, Tom Öresland, Pierre Michetti, Florian Froehlich. (2009) Appropriate maintenance treatment for Crohn's disease: Results of a multidisciplinary international expert panel — EPACT II. Journal of Crohn's and Colitis 3:4, 241-249
CrossRef121
Meenakshi Bewtra, James D. Lewis. (2009) Safety Profile of IBD: Lymphoma Risks. Gastroenterology Clinics of North America 38:4, 669-689
CrossRef122
David Schwartz. (2009) Anti-IL-12/23: The next big thing in IBD?. Inflammatory Bowel Diseases 15:12, 1927-1928
CrossRef123
Rodney Tehrani, Rochella A Ostrowski, Richard Hariman, Walter M. Jay. (2009) Review of Biologic Therapies. Neuro-Ophthalmology 33:6, 286-299
CrossRef124
Siba P. Raychaudhuri, Caroline T. Nguyen, Smriti K. Raychaudhuri, M. Eric Gershwin. (2009) Incidence and nature of infectious disease in patients treated with anti-TNF agents. Autoimmunity Reviews 9:2, 67-81
CrossRef125
Pierre Michetti, Marc Stelle, Pascal Juillerat, Miquel Gassull, Franz Josef Heil, Eduard Stange, Christian Mottet, Jean-Jacques Gonvers, Valérie Pittet, John-Paul Vader, Florian Froehlich, Christian Felley. (2009) Appropriateness of therapy for active Crohn's disease: Results of a multidisciplinary international expert panel—EPACT II. Journal of Crohn's and Colitis 3:4, 232-240
CrossRef126
Gert Van Assche, Séverine Vermeire, Paul Rutgeerts. (2009) Infliximab therapy for patients with inflammatory bowel disease: 10years on. European Journal of Pharmacology 623, S17-S25
CrossRef127
Joaquín Borrás-Blasco, Andrés Navarro-Ruiz, Consuelo Borrás, Elvira Casterá. (2009) Adverse Cutaneous Reactions Induced by TNF-α Antagonist Therapy. Southern Medical Journal 102:11, 1133-1140
CrossRef128
Gary P Toedter, Marion Blank, Yinghua Lang, Dion Chen, William J Sandborn, Willem J S de Villiers. (2009) Relationship of C-Reactive Protein With Clinical Response After Therapy With Ustekinumab in Crohn's Disease. The American Journal of Gastroenterology 104:11, 2768-2773
CrossRef129
Danial E Baker. (2009) Certolizumab pegol for the treatment of Crohn’s disease. Expert Review of Clinical Immunology 5:6, 683-691
CrossRef130
Filippo Mocciaro, Sara Renna, Ambrogio Orlando, Mario Cottone. (2009) Severe Cutaneous Psoriasis After Certolizumab Pegol Treatment: Report of a Case. The American Journal of Gastroenterology 104:11, 2867-2868
CrossRef131
Aarat M. Patel, Larry W. Moreland. (2009) Certolizumab pegol in active rheumatoid arthritis. Current Rheumatology Reports 11:5, 311-312
CrossRef132
Michael C Grimm. (2009) New and emerging therapies for inflammatory bowel diseases. Journal of Gastroenterology and Hepatology 24, S69-S74
CrossRef133
Bincy P. Abraham, Selvi Thirumurthi. (2009) Clinical significance of inflammatory markers. Current Gastroenterology Reports 11:5, 360-367
CrossRef134
Meaghan St. Charles, Sheila R. Weiss Smith, Robert Beardsley, Donald O. Fedder, Olivia Carter-Pokras, Raymond K. Cross. (2009) Gastroenterologists' prescribing of infliximab for Crohn's disease: A national survey. Inflammatory Bowel Diseases 15:10, 1467-1475
CrossRef135
Stephen B. Hanauer. (2009) Positioning biologic agents in the treatment of Crohn's disease. Inflammatory Bowel Diseases 15:10, 1570-1582
CrossRef136
Jean-Frédéric Colombel, William J. Sandborn, Remo Panaccione, Anne M. Robinson, Winnie Lau, Ju Li, Alexandra T. Cardoso. (2009) Adalimumab safety in global clinical trials of patients with Crohn's disease. Inflammatory Bowel Diseases 15:9, 1308-1319
CrossRef137
Tamás Molnár. (2009) TNF-α-blokkoló kezelés krónikus, ismeretlen eredetű gyulladásos bélbetegségekben. Orvosi Hetilap 150:38, 1773-1779
CrossRef138
Andrea Cassinotti, Simon Travis. (2009) Incidence and clinical significance of immunogenicity to infliximab in Crohn's disease: A critical systematic review. Inflammatory Bowel Diseases 15:8, 1264-1275
CrossRef139
Darin S Krygier, Hin Hin Ko, Brian Bressler. (2009) How to manage difficult Crohn’s disease: optimum delivery of anti-TNFs. Expert Review of Gastroenterology & Hepatology 3:4, 407-415
CrossRef140
G. R. LICHTENSTEIN, R. H. DIAMOND, C. L. WAGNER, A. A. FASANMADE, A. D. OLSON, C. W. MARANO, J. JOHANNS, Y. LANG, W. J. SANDBORN. (2009) Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Alimentary Pharmacology & Therapeutics 30:3, 210-226
CrossRef141
Brian G Feagan, Geoffroy Coteur, Seng Tan, Dorothy L Keininger, Stefan Schreiber. (2009) Clinically Meaningful Improvement in Health-Related Quality of Life in a Randomized Controlled Trial of Certolizumab Pegol Maintenance Therapy for Crohn's Disease. The American Journal of Gastroenterology 104:8, 1976-1983
CrossRef142
Gert Van Assche, Séverine Vermeire, Paul Rutgeerts. (2009) Immunosuppression in inflammatory bowel disease: traditional, biological or both?. Current Opinion in Gastroenterology 25:4, 323-328
CrossRef143
Alfredo Papa, Giammarco Mocci, Michele Bonizzi, Carla Felice, Gianluca Andrisani, Gianfranco Papa, Antonio Gasbarrini. (2009) Biological therapies for inflammatory bowel disease: controversies and future options. Expert Review of Clinical Pharmacology 2:4, 391-403
CrossRef144
Laura Yun, Stephen Hanauer. (2009) Selecting appropriate anti-TNF agents in inflammatory bowel disease. Expert Review of Gastroenterology & Hepatology 3:3, 235-248
CrossRef145
Anastasia Rivkin. (2009) Certolizumab pegol for the management of Crohn's disease in adults. Clinical Therapeutics 31:6, 1158-1176
CrossRef146
G. COTEUR, B. FEAGAN, D. L. KEININGER, M. KOSINSKI. (2009) Evaluation of the meaningfulness of health-related quality of life improvements as assessed by the SF-36 and the EQ-5D VAS in patients with active Crohn’s disease. Alimentary Pharmacology & Therapeutics 29:9, 1032-1041
CrossRef147
Anthony K Akobeng, Pieter C Stokkers, Anthony K Akobeng. 2009. Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. .
CrossRef148
Ramesh Srinivasan, Anthony K Akobeng, Anthony K Akobeng. 2009. Thalidomide and thalidomide analogues for induction of remission in Crohn's disease. .
CrossRef149
Paul Rutgeerts, Severine Vermeire, Gert Van Assche. (2009) Biological Therapies for Inflammatory Bowel Diseases. Gastroenterology 136:4, 1182-1197
CrossRef150
G. T. HO, A. MOWAT, L. POTTS, A. CAHILL, C. MOWAT, C. W. LEES, N. C. HARE, J. A. WILSON, R. BOULTON-JONES, M. PRIEST, D. A. WATTS, A. G. SHAND, I. D. ARNOTT, R. K. RUSSELL, D. C. WILSON, A. J. MORRIS, J. SATSANGI. (2009) Efficacy and complications of adalimumab treatment for medically-refractory Crohn’s disease: analysis of nationwide experience in Scotland (2004-2008). Alimentary Pharmacology & Therapeutics 29:5, 527-534
CrossRef151
L.-M. SHAO, M.-Y. CHEN, Q.-Y. CHEN, J.-T. CAI. (2009) Meta-analysis: the efficacy and safety of certolizumab pegol in Crohn’s disease. Alimentary Pharmacology & Therapeutics 29:6, 605-614
CrossRef152
Debra J. Helper. (2009) Medical management of Crohn's disease: A guide for radiologists. European Journal of Radiology 69:3, 371-374
CrossRef153
C. W. LEES, A. I. ALI, A. I. THOMPSON, G.-T. HO, R. O. FORSYTHE, L. MARQUEZ, C. J. COCHRANE, S. AITKEN, J. FENNELL, P. ROGERS, A. G. SHAND, I. D. PENMAN, K. R. PALMER, D. C. WILSON, I. D. R. ARNOTT, J. SATSANGI. (2009) The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Alimentary Pharmacology & Therapeutics 29:3, 286-297
CrossRef154
Ole Haagen Nielsen, Gerhard Rogler, Dieter Hahnloser, Ole Østergaard Thomsen. (2009) Diagnosis and management of fistulizing Crohn's disease. Nature Clinical Practice Gastroenterology & Hepatology 6:2, 92-106
CrossRef155
Gary R Lichtenstein, Stephen B Hanauer, William J Sandborn. (2009) Management of Crohn's Disease in Adults. The American Journal of Gastroenterology 104:2, 465-483
CrossRef156
A. OUSSALAH, A. BABOURI, J.-B. CHEVAUX, L. STANCU, I. TROUILLOUD, M. BENSENANE, T. BOUCEKKINE, M.-A. BIGARD, L. PEYRIN-BIROULET. (2009) Adalimumab for Crohn’s disease with intolerance or lost response to infliximab: a 3-year single-centre experience. Alimentary Pharmacology & Therapeutics 29:4, 416-423
CrossRef157
Alain M. Schoepfer, Stephan R. Vavricka, Janek Binek, Christian Felley, Martin Geyer, Michael Manz, Gerhard Rogler, Philippe de Saussure, Bernhard Sauter, Frank Seibold, Alex Straumann, Pierre Michetti. (2009) Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: Results of the FACTS survey. Inflammatory Bowel Diseasesn/a-n/a
CrossRef158
Tadakazu HISAMATSU, Toshifumi HIBI. (2009) Biologics in Current Therapy for Inflammatory Bowel Disease. Japanese Journal of Clinical Immunology 32:3, 168-179
CrossRef159
Marla C. Dubinsky, Ling Mei, Madison Friedman, Tanvi Dhere, Talin Haritunians, Hakon Hakonarson, Cecilia Kim, Joseph Glessner, Stephan R. Targan, Dermot P. McGovern, Kent D. Taylor, Jerome I. Rotter. (2009) Genome wide association (GWA) predictors of anti-TNFα therapeutic responsiveness in pediatric inflammatory bowel disease. Inflammatory Bowel Diseasesn/a-n/a
CrossRef160
Johannes Hausmann, Kai Zabel, Eva Herrmann, Oliver Schr
der. (2009) Methotrexate for maintenance of remission in chronic active Crohn's disease: Long-term single-center experience and meta-analysis of observational studies. Inflammatory Bowel DiseasesNA-NA
CrossRef161
Marla Dubinsky, Bincy Abraham, Uma Mahadevan. (2008) Management of the pregnant IBD patient. Inflammatory Bowel Diseases 14:12, 1736-1750
CrossRef162
Kelvin T. Thia, William J. Sandborn, James D. Lewis, Edward V. Loftus, Jr, Brian G. Feagan, A. Hillary Steinhart, Stephen B. Hanauer, Tore Persson, Bruce E. Sands. (2008) Defining the Optimal Response Criteria for the Crohn's Disease Activity Index for Induction Studies in Patients With Mildly to Moderately Active Crohn's Disease. The American Journal of Gastroenterology 103:12, 3123-3131
CrossRef163
Dennis J. Cada, Terri L. Levien, Danial E. Baker. (2008) Formulary Drug Reviews - Certolizumab Pegol. Hospital Pharmacy 43:12, 998-1010
CrossRef164
Gert Van Assche, Séverine Vermeire, Paul Rutgeerts. (2008) Management of loss of response to anti-TNF drugs: Change the dose or change the drug?. Journal of Crohn's and Colitis 2:4, 348-351
CrossRef165
Gert Assche, Séverine Vermeire, Paul Rutgeerts. (2008) Optimizing treatment of inflammatory bowel diseases with biologic agents. Current Gastroenterology Reports 10:6, 591-596
CrossRef166
Jean Bousquet, Raphael Chiron, Marc Humbert. (2008) Biologics in asthma: difficulties and drawbacks. Expert Opinion on Biological Therapy 8:12, 1921-1928
CrossRef167
Jakko van Ingen, Martin J Boeree, PN Richard Dekhuijzen, Dick van Soolingen. (2008) Mycobacterial disease in patients with rheumatic disease. Nature Clinical Practice Rheumatology 4:12, 649-656
CrossRef168
William J. Sandborn. (2008) Current Directions in IBD Therapy: What Goals Are Feasible With Biological Modifiers?. Gastroenterology 135:5, 1442-1447
CrossRef169
Michaell A. Huber. (2008) Gastrointestinal Illnesses and Their Effects on the Oral Cavity. Oral and Maxillofacial Surgery Clinics of North America 20:4, 625-634
CrossRef170
Klaus Kannengiesser, Christian Maaser, Torsten Kucharzik. (2008) Molecular pathogenesis of inflammatory bowel disease: relevance for novel therapies. Personalized Medicine 5:6, 609-626
CrossRef171
Robert Burakoff. (2008) Is it always therapeutically important to distinguish between Crohn's disease and ulcerative colitis?. Inflammatory Bowel Diseases 14:S2, S202-S203
CrossRef172
A. OUSSALAH, C. LACLOTTE, J.-B. CHEVAUX, M. BENSENANE, A. BABOURI, A.-A. SERRE, T. BOUCEKKINE, X. ROBLIN, M.-A. BIGARD, L. PEYRIN-BIROULET. (2008) Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience. Alimentary Pharmacology & Therapeutics 28:8, 966-972
CrossRef173
Edwin de Zoeten, Petar Mamula. (2008) What are the guidelines for using biologics in pediatric patients?. Inflammatory Bowel Diseases 14:S2, S259-S261
CrossRef174
Andre Franke, Annegret Fischer, Michael Nothnagel, Christian Becker, Nils Grabe, Andreas Till, Tim Lu, Joachim Müller–Quernheim, Michael Wittig, Alexander Hermann, Tobias Balschun, Sylvia Hofmann, Regina Niemiec, Sabrina Schulz, Jochen Hampe, Susanna Nikolaus, Peter Nürnberg, Michael Krawczak, Manfred Schürmann, Philip Rosenstiel, Almut Nebel, Stefan Schreiber. (2008) Genome-Wide Association Analysis in Sarcoidosis and Crohn's Disease Unravels a Common Susceptibility Locus on 10p12.2. Gastroenterology 135:4, 1207-1215
CrossRef175
William J. Sandborn, Brian G. Feagan, Richard N. Fedorak, Ellen Scherl, Mark R. Fleisher, Seymour Katz, Jewel Johanns, Marion Blank, Paul Rutgeerts. (2008) A Randomized Trial of Ustekinumab, a Human Interleukin-12/23 Monoclonal Antibody, in Patients With Moderate-to-Severe Crohn's Disease. Gastroenterology 135:4, 1130-1141
CrossRef176
R. Caprilli, E. Angelucci, V. Clemente. (2008) Recent advances in the management of Crohn's disease. Digestive and Liver Disease 40:9, 709-716
CrossRef177
Sandro Ardizzone, Gabriele Bianchi Porro. (2008) Is it possible to modify the clinical course of Crohn's disease?. Nature Clinical Practice Gastroenterology & Hepatology 5:8, 428-429
CrossRef178
David Schwartz. (2008) FIRST DO NO HARM??? RISK FACTORS FOR OPPORTUNISTIC INFECTIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. Evidence-Based Gastroenterology 9:3, 41-42
CrossRef179
Nils Lonberg. (2008) Fully human antibodies from transgenic mouse and phage display platforms. Current Opinion in Immunology 20:4, 450-459
CrossRef180
S. Nikolaus, S. Schreiber. (2008) Anti-TNF-Biologika in der Therapie chronisch-entzündlicher Darmerkrankungen. Der Internist 49:8, 947-954
CrossRef181
M Oliva-Hemker, JC Escher, D Moore, M Dubinksy, H Hildebrand, YKL Koda, S Murch, B Sandhu, JK Seo, MN Tanzi, B Warner. (2008) Refractory Inflammatory Bowel Disease in Children. Journal of Pediatric Gastroenterology and Nutrition 47:2, 266-272
CrossRef182
Gil Y. Melmed, Stephan R. Targan, Uma Yasothan, Delphine Hanicq, Peter Kirkpatrick. (2008) Certolizumab pegol. Nature Reviews Drug Discovery 7:8, 641-642
CrossRef183
Silvio Danese, Filippo Mocciaro, Luisa Guidi, Maria Lia Scribano, Michele Comberlato, Vito Annese, Elisabetta Colombo, Tommaso Stefanelli, Manuela Marzo, Marcello Vangeli, Raffaella Pulitano', Aldo Manca, Alessandro Armuzzi, Alberto Malesci, Cosimo Prantera, Mario Cottone. (2008) Successful induction of clinical response and remission with certolizumab pegol in Crohn's disease patients refractory or intolerant to infliximab: A real‐life multicenter experience of compassionate use. Inflammatory Bowel Diseases 14:8, 1168-1170
CrossRef184
A. Armuzzi, B. De Pascalis, P. Fedeli, F. De Vincentis, A. Gasbarrini. (2008) Infliximab in Crohn's disease: early and long-term treatment. Digestive and Liver Disease 40, S271-S279
CrossRef185
Helga-Paula Török, Burkhard Göke, Astrid Konrad. (2008) Pharmacogenetics of Crohn’s disease. Pharmacogenomics 9:7, 881-893
CrossRef186
Shane M Devlin, Remo Panaccione. (2008) Adalimumab for the treatment of Crohn's disease. Expert Opinion on Biological Therapy 8:7, 1011-1019
CrossRef187
J. LINDSAY, Y. S. PUNEKAR, J. MORRIS, G. CHUNG-FAYE. (2008) Health-economic analysis: cost-effectiveness of scheduled maintenance treatment with infliximab for Crohn’s disease - modelling outcomes in active luminal and fistulizing disease in adults. Alimentary Pharmacology & Therapeutics 28:1, 76-87
CrossRef188
Jennifer Jones, Remo Panaccione. (2008) Biologic therapy in Crohn??s disease: state of the art. Current Opinion in Gastroenterology 24:4, 475-481
CrossRef189
Laurent Peyrin–Biroulet, Pierre Deltenre, Nicolas de Suray, Julien Branche, William J. Sandborn, Jean–Frédéric Colombel. (2008) Efficacy and Safety of Tumor Necrosis Factor Antagonists in Crohn's Disease: Meta-Analysis of Placebo-Controlled Trials. Clinical Gastroenterology and Hepatology 6:6, 644-653
CrossRef190
Arthur Kaser, Herbert Tilg. (2008) Novel therapeutic targets in the treatment of IBD. Expert Opinion on Therapeutic Targets 12:5, 553-563
CrossRef191
Edward V. Loftus. (2008) CERTOLIZUMAB PEGOL REDUCES SYMPTOMS IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN??S DISEASE. Evidence-Based Gastroenterology 9:2, 32-33
CrossRef192
R Atreya, M F Neurath. (2008) New therapeutic strategies for treatment of inflammatory bowel disease. Mucosal Immunology 1:3, 175-182
CrossRef193
Csaba P Kovesdy, Kamyar Kalantar-Zadeh. (2008) Novel targets and new potential: developments in the treatment of inflammation in chronic kidney disease. Expert Opinion on Investigational Drugs 17:4, 451-467
CrossRef194
M. Cottone, A. Orlando, F. Mocciaro. (2008) Improving patients' QoL: how the success of treatment can improve workability. Digestive and Liver Disease Supplements 2:1, 17-18
CrossRef195
S. Ghosh. (2008) Top down therapy in Crohn's disease. Digestive and Liver Disease Supplements 2:1, 15-16
CrossRef196
Paul Rutgeerts, Stefan Schreiber, Brian Feagan, Dorothy L. Keininger, Liz O’Neil, Richard N. Fedorak, . (2008) Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFα, improves health-related quality of life in patients with moderate to severe Crohn’s disease. International Journal of Colorectal Disease 23:3, 289-296
CrossRef197
A. Armuzzi, F. De Vincentis, P. Fedeli, A. Gasbarrini. (2008) New developments in biologics therapy: what about from the medical point of view?. Digestive and Liver Disease Supplements 2:1, 25-26
CrossRef198
Andrew B Grossman, Robert N Baldassano. (2008) Specific considerations in the treatment of pediatric inflammatory bowel disease. Expert Review of Gastroenterology & Hepatology 2:1, 105-124
CrossRef199
David Schwartz. (2008) MAINTENANCE THERAPY WITH CERTOLIZUMAB PEGOL FOR CROHN??S DISEASE: A BETTER MOUSETRAP?. Evidence-Based Gastroenterology 9:1, 13-15
CrossRef200
G.-T. HO, L. SMITH, S. AITKEN, H. M. LEE, T. TING, J. FENNELL, C. W. LEES, K. R. PALMER, I. D. PENMAN, A. G. SHAND, I. D. ARNOTT, J. SATSANGI. (2008) The use of adalimumab in the management of refractory Crohn’s disease. Alimentary Pharmacology & Therapeutics 27:4, 308-315
CrossRef201
Silvio Danese, Tommaso Stefanelli, Paolo Omodei, Stefania Zatelli, Cristiana Bonifacio, Luca Balzarini, Alessandro Repici, Alberto Malesci. (2008) Successful treatment of fistulizing Crohn's disease with certolizumab pegol. Inflammatory Bowel Diseases 14:2, 292-293
CrossRef202
A. K. AKOBENG. (2008) Review article: the evidence base for interventions used to maintain remission in Crohn’s disease. Alimentary Pharmacology & Therapeutics 27:1, 11-18
CrossRef203
V. S. THEIS, J. M. RHODES. (2008) Review article: minimizing tuberculosis during anti-tumour necrosis factor-alpha treatment of inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 27:1, 19-30
CrossRef204
Brian W Behm, Stephen J Bickston, Stephen J Bickston. 2008. .
CrossRef205
Francesco M Veronese, Anna Mero. (2008) The Impact of PEGylation on Biological Therapies. BioDrugs 22:5, 315-329
CrossRef206
Tim Bourne, Gianluca Fossati, Andrew Nesbitt. (2008) A PEGylated Fab′ Fragment against Tumor Necrosis Factor for the Treatment of Crohn Disease. BioDrugs 22:5, 331-337
CrossRef207
Stephen B. Hanauer. (2007) Biologic therapy for inflammatory bowel disease comes of age. Current Gastroenterology Reports 9:6, 485-488
CrossRef208
Fernando S. Velayos, William J. Sandborn. (2007) Positioning biologic therapy for Crohn’s disease and ulcerative colitis. Current Gastroenterology Reports 9:6, 521-527
CrossRef209
Carmen Cuffari. (2007) Anti-TNF therapy in Crohn’s disease: a balance between a targeted therapeutic approach and drug-induced immunogenicity. Expert Review of Gastroenterology & Hepatology 1:2, 233-237
CrossRef210
J.C. Preiß, R. Duchmann. (2007) Neue Therapieverfahren bei chronisch-entzündlichen Darmerkrankungen. Der Gastroenterologe 2:6, 423-429
CrossRef211
(2007) Anti-TNF Antibodies for Crohn's Disease. New England Journal of Medicine 357:16, 1662-1662
Full Text212
Trevor A Winter, William J Sandborn, Willem JS de Villiers, Stefan Schreiber. (2007) Treatment of Crohn’s disease with certolizumab pegol. Expert Review of Clinical Immunology 3:5, 683-694
CrossRef213
Lewis, James D., . (2007) Anti-TNF Antibodies for Crohn's Disease — In Pursuit of the Perfect Clinical Trial. New England Journal of Medicine 357:3, 296-298
Full Text214
Sandborn, William J., Feagan, Brian G., Stoinov, Simeon, Honiball, Pieter J., Rutgeerts, Paul, Mason, David, Bloomfield, Ralph, Schreiber, Stefan, . (2007) Certolizumab Pegol for the Treatment of Crohn's Disease. New England Journal of Medicine 357:3, 228-238
Full Text215
Pascal Juillerat, Valérie Pittet, Christian Felley, Christian Mottet, Florian Froehlich, John-Paul Vader, Jean-Jacques Gonvers, Pierre Michetti. (2007) Drug Safety in Crohn’s Disease Therapy. Digestion 76:2, 161-168
CrossRef216
Pierre Michetti, Christian Mottet, Pascal Juillerat, Valérie Pittet, Christian Felley, John-Paul Vader, Jean-Jacques Gonvers, Florian Froehlich. (2007) Severe and Steroid-Resistant Crohn’s Disease. Digestion 76:2, 99-108
CrossRef
- Letters
