Original Article
Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome
N Engl J Med 2009; 360:2416-2425June 4, 2009
- Abstract
Background
The cryopyrin-associated periodic syndrome (CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human anti–interleukin-1β monoclonal antibody.
Methods
We performed a three-part, 48-week, double-blind, placebo-controlled, randomized withdrawal study of canakinumab in patients with CAPS. In part 1, 35 patients received 150 mg of canakinumab subcutaneously. Those with a complete response to treatment entered part 2 and were randomly assigned to receive either 150 mg of canakinumab or placebo every 8 weeks for up to 24 weeks. After the completion of part 2 or at the time of relapse, whichever occurred first, patients proceeded to part 3 and received at least two more doses of canakinumab. We evaluated therapeutic responses using disease-activity scores and analysis of levels of C-reactive protein (CRP) and serum amyloid A protein (SAA).
Results
In part 1 of the study, 34 of the 35 patients (97%) had a complete response to canakinumab. Of these patients, 31 entered part 2, and all 15 patients receiving canakinumab remained in remission. Disease flares occurred in 13 of the 16 patients (81%) receiving placebo (P<0.001). At the end of part 2, median CRP and SAA values were normal (<10 mg per liter for both measures) in patients receiving canakinumab but were elevated in those receiving placebo (P<0.001 and P=0.002, respectively). Of the 31 patients, 28 (90%) completed part 3 in remission. In part 2, the incidence of suspected infections was greater in the canakinumab group than in the placebo group (P=0.03). Two serious adverse events occurred during treatment with canakinumab: one case of urosepsis and an episode of vertigo.
Conclusions
Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS. (ClinicalTrials.gov number, NCT00465985.)
Media in This Article
Figure 1
Response of Rash to Canakinumab in a Patient with the Cryopyrin-Associated Periodic Syndrome (CAPS).Figure 2
Response to Canakinumab, as Compared with Placebo.Article Activity
- Article
The cryopyrin-associated periodic syndrome (CAPS) comprises a spectrum of apparently distinct, rare, inherited inflammatory disorders of increasing severity, including the familial cold autoinflammatory syndrome, the Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disorder (also known as the chronic infantile neurologic, cutaneous, and articular syndrome). Patients with these disorders have severe fatigue, fever, and influenza-like myalgia from infancy, together with chronic anemia and inflammation of the skin, eyes, bones, joints, and meninges. Clinical features include rash, conjunctivitis, arthritis, chronic meningitis, sensorineural deafness, and intellectual impairment. Systemic AA amyloidosis that causes renal failure and usually results in death within 5 to 10 years develops in approximately 25% of patients.1-3
CAPS is associated with mutations in NLRP3, the gene encoding cryopyrin, a component of the interleukin-1 inflammasome that regulates the production of interleukin-1β.4-6 As a key proinflammatory cytokine mediating local and systemic responses to infection and tissue injury, interleukin-1β can induce a range of responses, including fever, pain sensitization, bone and cartilage destruction, and the acute-phase plasma protein response. The pivotal pathogenic role of interleukin-1 in CAPS has been demonstrated by the achievement of complete responses after treatment with the recombinant interleukin-1–receptor antagonist, anakinra.7-10
Canakinumab (ACZ885, Novartis Pharma) is a fully human anti–interleukin-1β monoclonal antibody that selectively blocks interleukin-1β and has no cross-reactivity with other characterized interleukin-1 family members, including interleukin-1α and interleukin-1Ra.11 A preliminary open-label study of canakinumab in patients with CAPS has been carried out.12-14 We describe here the response to treatment with canakinumab in patients with CAPS in a multicenter, randomized, double-blind, placebo-controlled clinical study.
Methods
Dose Determination
We selected a subcutaneous dose of 150 mg of canakinumab (or 2 mg per kilogram of body weight for patients weighing 40 kg [88 lb] or less) every 8 weeks on the basis of a pharmacokinetic and pharmacodynamic model showing a predicted relapse rate of 3% after the first dose and 1% subsequently.15 (For additional details, see the Supplementary Appendix, available with the full text of this article at NEJM.org.)
Study Design
The study, which was approved by the independent ethics committee at each participating center, consisted of three parts (Fig. 1 in the Supplementary Appendix). Part 1 was an open-label treatment period in which a single dose of canakinumab was administered; the response was assessed during the following 8 weeks. Part 2 was a double-blind withdrawal period, in which patients who had a sustained complete response in part 1 were randomly assigned to receive either canakinumab or placebo every 8 weeks for up to 24 weeks. At the end of part 2 or at the time of relapse, whichever occurred first, patients immediately entered the open-label part 3 of the study, in which they received canakinumab every 8 weeks for a minimum of 16 weeks, for a total study duration of 48 weeks.
All patients entering the study or their parents provided written informed consent. The sponsor (Novartis Pharma) funded the study and held the data. The investigators had unrestricted access to the data and to the analyses. All the authors vouch for the completeness and accuracy of the data and analyses presented. The decision to submit the manuscript for publication was made by the academic authors and the clinical communication leader at Novartis Pharma. Two of the academic authors wrote the first draft of the manuscript; all authors approved the final draft.
Patients
Patients who had CAPS associated with an NLRP3 mutation and who required treatment were eligible for enrollment if they were between the ages of 4 and 75 years and weighed at least 15 kg (33 lb) but less than 100 kg (220 lb). Patients who had previously received treatment with anakinra, rilonacept, or canakinumab were eligible to participate immediately after such treatment had been discontinued and their disease had relapsed. Administration of other investigational biologic agents was not permitted during the 8 weeks before the baseline visit (for details, see the Supplementary Appendix).
Assessments of Disease Activity
At screening and monthly follow-up visits, physicians assessed global disease activity and each of the following symptoms: urticarial rash, arthralgia, myalgia, headache or migraine, conjunctivitis, fatigue or malaise, and other symptoms related or unrelated to CAPS. The assessment was performed with the use of a 5-point scale for disease activity: absent, minimal, mild, moderate, or severe. Blood samples were collected to measure levels of acute-phase reactants, C-reactive protein (CRP), and serum amyloid A protein (SAA) and to assess hematologic and biochemical markers and immunogenicity. Blood samples were analyzed in a central laboratory by pathologists who were unaware of study-group assignments.
Patients performed a global assessment of their symptoms together with assessments of each of the following symptoms: fever or chills, rash, joint or muscle pain, eye discomfort or redness, fatigue, headache, and other symptoms. The assessments were performed with the use of the same 5-point scale used by physicians. Adverse events were recorded throughout the study; the severity of such events and their relationship to the administration of a study drug were recorded. Patients were asked about the occurrence of any injection-site reactions.
Study Definitions
A complete response to treatment was defined as a global assessment of no or minimal disease activity by a physician, an assessment of no or minimal rash, and a value for both serum CRP and SAA that was within the normal range (<10 mg per liter for both measures). Relapse was defined as a value for either CRP or SAA of more than 30 mg per liter, accompanied by a physician's assessment of global disease activity that was greater than minimal or that was minimal and accompanied by a rash that was assessed as more than minimal. Patients in part 1 were eligible for entry into part 2 if they had had a complete response to canakinumab by day 15 with no relapse by week 8.
Outcome Measures
The primary outcome measure was the proportion of patients with a relapse of CAPS during canakinumab treatment, as compared with placebo, in part 2. Secondary outcome measures included the proportion of patients with a complete response in part 1, values of inflammatory markers, global assessments by physicians and patients, and safety and tolerability.
Statistical Analysis
The primary analysis was based on the intention-to-treat population in part 2. Patients who met the criteria for relapse or who discontinued treatment prematurely in part 2 for any reason were considered to have had a disease relapse. The study groups were compared with the use of a stratified Fisher's exact test. The time until disease flare in part 2 was assessed with the use of a Cox proportional-hazards regression model. Kaplan–Meier estimates were plotted against time. Changes in inflammatory markers from week 8 were analyzed with the use of a stratified Wilcoxon rank-sum test. Fisher's exact test was used to compare the incidence of infections between study groups in part 2. All statistical tests were two-sided at a significance level of 0.05.
Results
Patients
We screened 41 patients for entry in the study; of these patients, 6 were deemed to be ineligible (Fig. 2 in the Supplementary Appendix). Thus, 35 patients from 11 centers in five countries (France, Germany, India, the United Kingdom, and the United States) were enrolled in the study. Demographic and disease characteristics are summarized in Table 1Table 1
Demographic and Disease Characteristics of the Patients, According to Study-Group Assignment in Part 2..Initial Open-Label Phase (Part 1)
Of 35 patients enrolled in part 1, 34 (97%) had a complete response to treatment with a single dose of canakinumab, according to the protocol definition. Symptoms of CAPS diminished within 24 hours in patients who had a response (Figure 1Figure 1
Response of Rash to Canakinumab in a Patient with the Cryopyrin-Associated Periodic Syndrome (CAPS).). A complete response was achieved by day 8 in 25 patients, by day 15 in 8 patients, and by day 29 in 1 patient. The patient who had a complete response on day 29 had a clinical response by day 15 but had elevated CRP and SAA values at this time, which were attributed to a self-limiting viral infection. The one patient who did not have a complete response had self-injected the medication. Canakinumab levels in this patient were substantially lower than expected and were consistent with administration of an incomplete dose. This patient was withdrawn from the study.Three patients who had a complete response after a single dose of canakinumab did not proceed to part 2: one patient withdrew from the study because of a failure to maintain a satisfactory therapeutic response, and two others had mild conjunctivitis on the day of randomization and were reluctant to receive placebo. Thus, 31 patients (89%) proceeded to part 2.
Double-Blind Withdrawal Phase (Part 2)
Relapse
During the double-blind period, all 15 patients in the canakinumab group remained in remission. In contrast, 13 of the 16 patients (81%) in the placebo group had a disease flare (P<0.001). The median time until the disease flare was 100 days from the start of part 2 (i.e., approximately 22 weeks after the initial dose of canakinumab in part 1) (Figure 2AFigure 2
Response to Canakinumab, as Compared with Placebo.).Inflammatory Markers
CRP levels remained within the normal range among patients in the canakinumab group (median, 2.3 mg per liter) but rose in the placebo group (median, 24.4 mg per liter) (Table 2Table 2
Inflammatory Markers and Assessments by Physicians and Patients, According to Study-Group Assignment in Parts 2 and 3. and Figure 2B). During the course of part 2, the mean increase in CRP level was 19.9 mg per liter in the placebo group, as compared with a mean increase of 1.1 mg per liter in the canakinumab group (P<0.001).SAA levels remained within the normal range among patients in the canakinumab group (median, 6.1 mg per liter) but rose in the placebo group (median, 43.4 mg per liter) (Table 2). Over the course of part 2, the mean increase in SAA level was 71.1 mg per liter in the placebo group, as compared with a mean increase of 2.3 mg per liter in the canakinumab group (P=0.002).
Assessments of Disease Activity
By the end of part 2, all patients in the canakinumab group were rated as having no or minimal disease activity by physicians, as compared with four patients (25%) in the placebo group (P<0.001). Rash was completely absent in 14 of 15 patients (93%) receiving canakinumab, as compared with 5 of 16 patients (31%) receiving placebo (Table 2).
At the end of part 2, 6 of 15 patients (40%) in the canakinumab group reported having a complete absence of symptoms, as compared with no patients in the placebo group (Table 2). Four patients in the canakinumab group reported having severe symptoms associated with other disorders: two patients in one household had acute gastroenteritis, a third patient had painful fibromyalgia, and a fourth had migraine (see Table 2 for details). No severe symptoms were reported by the patients in the placebo group at the end of part 2 (P=0.28 for the comparison between groups).
Subsequent Open-Label Phase (Part 3)
All 31 patients from part 2 entered part 3, and 29 patients (94%) completed the protocol. Two patients discontinued therapy, one because of a therapeutic response that the patient considered to be unsatisfactory 138 days after entering the study and the other because of recurrent Escherichia coli urinary tract infections.
Clinical and biochemical remission of CAPS was sustained in 28 of the 29 patients (97%) who completed part 3. One patient had a relapse on the last day (day 336), 62 days after receiving the last dose of canakinumab. Among patients who received placebo in part 2 and were in a CAPS flare state on entry to part 3, CRP and SAA values decreased to medians of 2.3 and 5.8 mg per liter, respectively, at the end of the study. Median CRP and SAA values remained suppressed, at 1.9 and 5.1 mg per liter, respectively, in the 15 patients who received canakinumab throughout the study.
At the final assessment of part 3, a total of 30 of the 31 patients who had entered this final phase of the study (97%) had no or minimal disease activity, according to the assessment of physicians, and the remaining patient had mild disease activity. Rash was absent in 29 of the 31 patients (94%) and was minimal in the other 2 patients. Either no or minimal symptoms were reported by 26 of the 31 patients (84%), mild symptoms were reported by 1 patient, moderate symptoms by 2 patients, and severe symptoms by 1 patient, who also had fibromyalgia; data were missing for 1 patient.
Adverse Events
No deaths or life-threatening adverse effects occurred. Two patients had serious adverse events while receiving canakinumab in part 3, and both of them discontinued therapy, as noted above. One of the two patients had a lower urinary tract infection requiring hospital admission; the other patient had an episode of vertigo accompanied by acute closed-angle glaucoma, which was attributable to CAPS, and withdrew from the study because of an unsatisfactory therapeutic effect. The use of canakinumab was not associated with any clear pattern of adverse events other than an increase in the rate of suspected infections (P=0.03) (Table 3Table 3
Adverse Events.). The fact that the mean study-drug exposure in part 2 was greater in the canakinumab group (169 days) than in the placebo group (118 days) may have contributed to this increased incidence of suspected infections.In parts 1 and 2, most patients (>91%) reported having no injection-site reactions; four patients reported a mild reaction. In part 2, a total of 13 of the 15 patients (87%) receiving canakinumab and 15 of the 16 patients (94%) receiving placebo reported no injection-site reactions. There were no reports of severe injection-site reactions. No immunogenicity against canakinumab was detected, and no safety issues emerged from hematologic monitoring, urinalysis, or other assessments (for details, see the Supplementary Appendix).
Discussion
Our study of canakinumab showed rapid, substantial, and sustained clinical efficacy of this interleukin-1β inhibitor in patients with CAPS. The safety data, though limited, were generally reassuring, with only two serious adverse events occurring, no evidence of immunogenicity, and only occasional, mild injection-site reactions.
The beneficial effect of canakinumab on patients' symptoms had a prolonged duration of action, probably because canakinumab has a plasma half-life of 28 to 30 days and perhaps because it has a disease-modifying effect through autocrine down-regulation of interleukin-1β production.15 Of the 35 patients who received canakinumab, 34 had a complete response after the administration of a single dose. At the end of the 24-week, double-blind, placebo-controlled phase, all patients who received canakinumab remained in remission, as compared with 25% of patients who received placebo. A noteworthy benefit of the complete clinical response to canakinumab and its associated effect in halting an extensive cascade of proinflammatory cytokine activity was a reduction of acute-phase SAA production to normal levels, which, in theory, should reduce the long-term risk of AA amyloidosis.3
Symptom assessments by patients also showed a sustained benefit of canakinumab therapy, with 40% reporting a complete absence of symptoms, as compared with none in the placebo group. However, a limitation of the study, which was associated with its necessarily small size, was the presence of symptoms (headache, fever, and fatigue) attributed to non-CAPS disorders in four patients at the key time point at the end of part 2. As a result, patient-reported symptoms at this time did not differ significantly between the canakinumab group and the placebo group. Detailed examination of the records for these four patients revealed that they had all had a good response to canakinumab, and their physicians had rated their CAPS disease activity as absent or minimal in association with normal CRP and SAA measurements. At the end of part 3, a total of 84% of patients assessed their symptoms as absent or minimal.
The study also had a number of other limitations. First, the use of a withdrawal design with an open-label run-in period and the selection of patients who had a response to treatment might have introduced a bias toward a higher response rate in the treatment group during the randomized phase of the study than in the overall patient population.16 On the other hand, the withdrawal of patients who had a relapse from the double-blind phase might have meant that the maximum difference between placebo and active treatment was not reached. However, the response rate in part 1 was high, and the criteria for response were stringent. Moreover, this type of study design is generally considered appropriate for rare, severe conditions, in which the anticipation of a good response (as seen in early-phase studies12-15) renders it unethical to treat patients for a prolonged period with placebo.16 Second, the small number of patients in the study meant that the analyses were not powered to detect statistically significant differences between the study groups in secondary end points, such as assessments by patients. There was also an imbalance in randomization, with more female patients in the group receiving canakinumab treatment, but it is unlikely that this was a significant confounding factor, since sex differences have not been observed in studies with respect to molecular features, symptoms, or treatment responses in patients with CAPS.
The efficacy of canakinumab in the treatment of CAPS demonstrates that interleukin-1β is an important factor in the pathogenesis of this disorder. The NLRP3 mutations that are associated with CAPS result in increased activity of the enzyme caspase-1, which increases secretion of interleukin-1β and downstream activation of other proinflammatory cytokines. Other interleukin-1 inhibitors (anakinra and rilonacept) also have demonstrated efficacy in CAPS.7,10 However, the prolonged duration of action of canakinumab and low incidence of injection-site reactions may confer certain advantages for canakinumab, since both anakinra and rilonacept are frequently associated with injection-site reactions, and both require more frequent administration (daily for anakinra and weekly for rilonacept).2,8,9,17-20
In general, the infections seen in this small study were not serious, though suspected infections were significantly more prevalent in patients receiving canakinumab than in those receiving placebo. One patient had recurrent urinary tract infections with an antibiotic-resistant organism, which may have been affected by interleukin-1 blockade. Vigilance with respect to such infections will continue to be required. In conclusion, administration of canakinumab once every 8 weeks was associated with substantial control of inflammatory disease in children and adults with CAPS.
Supported by Novartis Pharma.
Drs. Lachmann and Hawkins report receiving consulting fees from Novartis; Dr. Kone-Paut, receiving lecture fees from Novartis; Dr. Kuemmerle-Deschner, receiving consulting fees from Novartis, Bristol-Meyers Squibb, and Roche and grant support from Novartis; and Dr. Gitton, Mr. Widmer, and Ms. Patel, being employees of Novartis and having an equity interest in the company. No other potential conflict of interest relevant to this article was reported.
We thank the patients who participated in the study; Nicole Davis and Sigrid Malfait of Novartis Pharma for their help in running the study; Kerstin Kroeger of Novartis Pharma for performing the immunogenicity evaluations; Kirstin Stricker, clinical communication leader, Novartis Pharma, for her critical review; Karine Lheritier for assistance in statistical programming; and Oxford PharmaGenesis for assistance in collating the comments of authors and in the preparation of an earlier version of the manuscript.
Source Information
From the University College London Medical School, London (H.J.L., P.N.H.); Hôpital Kremlin Bicetre, Le Kremlin Bicetre (I.K.-P.), and Université Paris-Descartes and Hôpital Necker-Enfants Malades (P.Q.) — both in Paris; Universitätsklinik, Tübingen, Germany (J.B.K.-D.); the University of California at San Francisco, San Francisco (K.S.L.); Université de Lille 2, Hôpital Claude Huriez, Lille CEDEX, France (E.H.); Novartis Pharma, Basel, Switzerland (X.G., A.W.); and Novartis Pharma, East Hanover, NJ (N.P.).
Address reprint requests to Dr. Lachmann at the National Amyloidosis Centre, UCL Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom, or at h.lachmann@medsch.ucl.ac.uk.
Members of the Canakinumab in Cryopyrin-Associated Periodic Syndrome (CAPS) Study Group are listed in the Appendix.
Appendix
The following investigators were members of the Canakinumab in CAPS Study Group: S. Madhoo, UCL Medical School, London; J.-M. Berthelot, Hôpital Hôtel Dieu, Nantes, France; C. Jorgensen, Hôpital Lapeyronie, Montepellier, France; S. Morell-Dubois, Hôpital Claude Huriez, Lille, France; R. Mouy, Hôpital Necker–Enfants Malades, Paris; I. Marie and S. Lacassagne, Hôpital Kremlin Bicetre, Le Kremlin Bicetre, Paris; R. Chaturvedi, Pushpawati Singhania Research Institute, New Delhi, India; C. Vargas, Hospital Universitario Virgen Macarena, Seville, Spain; J.A. Block, Rush–Presbyterian–St. Luke's Medical Center, Chicago; and J. Smith, University of Wisconsin, Madison.
- References
References
1
Muckle TJ ,Wells M . Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. Q J Med 1962;31:235-248
Web of Science | Medline2
Hawkins PN ,Lachmann HJ ,Aganna E ,McDermott MF . Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthritis Rheum 2004;50:607-612
CrossRef | Web of Science | Medline3
Lachmann HJ ,Goodman HJ ,Gilbertson JA , et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med 2007;356:2361-2371
Full Text | Web of Science | Medline4
Church LD ,Cook GP ,McDermott MF . Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol 2008;4:34-42
CrossRef | Web of Science | Medline5
Dinarello CA . The many worlds of reducing interleukin-1. Arthritis Rheum 2005;52:1960-1967
CrossRef | Web of Science | Medline6
Maksimovic L ,Stirnemann J ,Caux F , et al. New CIAS1 mutation and anakinra efficacy in overlapping of Muckle-Wells and familial cold autoinflammatory syndromes. Rheumatology (Oxford) 2008;47:309-310
CrossRef | Web of Science | Medline7
Leslie KS ,Lachmann HJ ,Bruning E , et al. Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations. Arch Dermatol 2006;142:1591-1597
CrossRef | Web of Science | Medline8
Ross JB ,Finlayson LA ,Klotz PJ , et al. Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up. J Cutan Med Surg 2008;12:8-16
Web of Science | Medline9
Yamazaki T ,Masumoto J ,Agematsu K , et al. Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome. Arthritis Rheum 2008;58:864-868
CrossRef | Web of Science | Medline10
Hoffman HM ,Throne ML ,Amar NJ , et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum 2008;58:2443-2452
CrossRef | Web of Science | Medline11
Alten R ,Gram H ,Joosten LA , et al. The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis. Arthritis Res Ther 2008;10:R67-R67
CrossRef | Web of Science | Medline12
Lachmann HJ ,Jung T ,Felix SD , et al. Treatment of cryopyrin associated periodic fever syndrome with a fully human anti-IL-1beta monoclonal antibody (ACZ885): results from a subcutaneous administration study. Clin Exp Rheumatol 2008;26:181-181
Web of Science13
Kuemmerle-Deschner JB ,Tzaribachev N ,Hansmann S , et al. Long-lasting response to ACZ885 (a new human IgG1 anti-IL-1β monoclonal antibody) in patients with Muckle-Wells Syndrome (MWS). Clin Exp Rheumatol 2008;26:180-180
Web of Science14
Kummerle-Deschner J ,Tzaribachev N ,Hansmann S , et al. Long lasting response to ACZ885 in patients with Muckle-Wells-Syndrome (MWS). Ann Rheum Dis 2008;67:Suppl II:104-10415
Lachmann HJ, Lowe P, Felix SD, et al. In vivo regulation of interleukin-1beta in patients with cryopyrin associated periodic syndromes. J Exp Med 2009 April 13 (Epub ahead of print).
16
Temple RJ . Special study designs: early escape, enrichment, studies in non-responders. Commun Stat 1994;23:499-531
CrossRef | Web of Science17
Kalliolias GD ,Liossis SN . The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis. Expert Opin Investig Drugs 2008;17:349-359
CrossRef | Web of Science | Medline18
Karanikolas G ,Charalambopoulos D ,Vaiopoulos G , et al. Adjunctive anakinra in patients with active rheumatoid arthritis despite methotrexate, or leflunomide, or cyclosporin-A monotherapy: a 48-week, comparative, prospective study. Rheumatology (Oxford) 2008;47:1384-1388
CrossRef | Web of Science | Medline19
Maier J ,Birkenfeld G ,Pfirstinger J ,Scholmerich J ,Fleck M ,Bruhl H . Effective treatment of steroid refractory adult-onset Still's disease with anakinra. J Rheumatol 2008;35:939-941
Web of Science | Medline20
Furst DE ,Breedveld FC ,Kalden JR , et al. Updated consensus statement on biological agents, specifically tumour necrosis factor alpha (TNFalpha) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005. Ann Rheum Dis 2005;64:Suppl 4:iv2-iv14
CrossRef | Web of Science | Medline
- Citing Articles (122)
Citing Articles
1
Monique P. Curran. (2012) Canakinumab. BioDrugs 26:1, 53-59
CrossRef2
Shabina Habibi, Athimalaipet V Ramanan. (2012) Review of biologics in children with rheumatic diseases. International Journal of Clinical Rheumatology 7:1, 81-93
CrossRef3
R. Gurion, T. J. A. Lehman, L. N. Moorthy. (2012) Systemic Arthritis in Children: A Review of Clinical Presentation and Treatment. International Journal of Inflammation 2012, 1-16
CrossRef4
R W J Lee, A D Dick. (2012) Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation. Eye 26:1, 17-28
CrossRef5
M Dagenais, A Skeldon, M Saleh. (2012) The inflammasome: in memory of Dr. Jurg Tschopp. Cell Death and Differentiation 19:1, 5-12
CrossRef6
Jeffrey H. Dunn, Lixia Z. Ellis, Mayumi Fujita. (2012) Inflammasomes as molecular mediators of inflammation and cancer: Potential role in melanoma. Cancer Letters 314:1, 24-33
CrossRef7
B. Kortus-Gotze, J. Hoyer. (2011) Successful renal transplantation in Muckle-Wells syndrome treated with anti-IL-1 -monoclonal antibody. NDT Plus 4:6, 404-405
CrossRef8
Gareth Rees. (2011) Industry Update: The latest developments in therapeutic delivery. Therapeutic Delivery 2:12, 1527-1533
CrossRef9
Karoline Krause, Eugen Feist, Michael Fiene, Tilmann Kallinich, Marcus Maurer. (2011) Complete remission in 3 of 3 anti-IL-6–treated patients with Schnitzler syndrome. Journal of Allergy and Clinical Immunology
CrossRef10
Heleen D. de Koning, Joost Schalkwijk, Jos W.M. van der Meer, Anna Simon. (2011) Successful canakinumab treatment identifies IL-1β as a pivotal mediator in Schnitzler syndrome. Journal of Allergy and Clinical Immunology 128:6, 1352-1354
CrossRef11
Raquel Cuchacovich, Ignacio Garcia-Valladares, Luis R Espinoza. (2011) Pleiotropic effects of inflammasome modulation in chronic gout and associated comorbidities: potential therapeutic implications. International Journal of Clinical Rheumatology 6:6, 669-676
CrossRef12
Borbála Pazár Maldonado, Alexander So. (2011) Canakinumab for the treatment of gout. International Journal of Clinical Rheumatology 6:6, 605-615
CrossRef13
Giovanni Germano, Alberto Mantovani, Paola Allavena. (2011) Targeting of the innate immunity/inflammation as complementary anti-tumor therapies. Annals of Medicine 43:8, 581-593
CrossRef14
Isabelle Koné-Paut. (2011) Rhumatologie pédiatrique : quelles avancées ?. Revue du Rhumatisme Monographies
CrossRef15
Linda Rossi-Semerano, Isabelle Koné-Paut. (2011) Focus sur les inhibiteurs de l’interleukine 1. Revue du Rhumatisme Monographies
CrossRef16
Daria B Crittenden, Han Na Kim, Mark C Fisher, David S Goldfarb, Michael H Pillinger. (2011) New and emerging therapies for gout. Clinical Investigation 1:11, 1563-1575
CrossRef17
Aarat M. Patel, Kathryn S. Torok. (2011) Canakinumab for the treatment of adult and pediatric cryopyrin-associated periodic syndromes (CAPS). Drug Development Research 72:7, 553-560
CrossRef18
Raphaela Goldbach-Mansky. (2011) Update on Monogenic Autoinflammatory diseases: The role of IL-1 and an emerging role for cytokines beyond IL-1 …. Clinical & Experimental Immunologyno-no
CrossRef19
Varol Ulas Ozkurede, Luigi Franchi. (2011) Role of inflammasomes in autoinflammatory syndromes. Clinical & Experimental Immunologyno-no
CrossRef20
Luca Cantarini, Donato Rigante, Maria Giuseppina Brizi, Orso Maria Lucherini, Gian Domenico Sebastiani, Antonio Vitale, Valentina Gianneramo, Mauro Galeazzi. (2011) Clinical and biochemical landmarks in systemic autoinflammatory diseases. Annals of Medicine1-10
CrossRef21
Thirusha Lane, Helen J. Lachmann. (2011) The Emerging Role of Interleukin-1β in Autoinflammatory Diseases. Current Allergy and Asthma Reports 11:5, 361-368
CrossRef22
Paul M Ridker, Tom Thuren, Andrew Zalewski, Peter Libby. (2011) Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: Rationale and Design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). American Heart Journal 162:4, 597-605
CrossRef23
P. Menu, J. E. Vince. (2011) The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. Clinical & Experimental Immunology 166:1, 1-15
CrossRef24
Donato Rigante. (2011) The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmunity Reviews
CrossRef25
Gabor L. Horvath, Jacob E. Schrum, Christine M. De Nardo, Eicke Latz. (2011) Intracellular sensing of microbes and danger signals by the inflammasomes. Immunological Reviews 243:1, 119-135
CrossRef26
Robert Zeiser, Olaf Penack, Ernst Holler, Marco Idzko. (2011) Danger signals activating innate immunity in graft-versus-host disease. Journal of Molecular Medicine 89:9, 833-845
CrossRef27
Mohamed Lamkanfi, Lieselotte Vande Walle, Thirumala-Devi Kanneganti. (2011) Deregulated inflammasome signaling in disease. Immunological Reviews 243:1, 163-173
CrossRef28
Lori Broderick, Louanne M. Tourangeau, Arthur Kavanaugh, Stephen I. Wasserman. (2011) Biologic modulators in allergic and autoinflammatory diseases. Current Opinion in Allergy and Clinical Immunology 11:4, 355-360
CrossRef29
Yelda Bilginer, Tekin Akpolat, Seza Ozen. (2011) Renal amyloidosis in children. Pediatric Nephrology 26:8, 1215-1227
CrossRef30
Christine Bangert, Patrick M. Brunner, Georg Stingl. (2011) Immune functions of the skin. Clinics in Dermatology 29:4, 360-376
CrossRef31
Gerd Horneff. (2011) Treatment options with biologics for juvenile idiopathic arthritis. International Journal of Clinical Rheumatology 6:3, 305-323
CrossRef32
L. Newell, S. August, V. Foria, K. Godfrey. (2011) Lifelong urticaria and multiple unexplained systemic symptoms. Clinical and Experimental Dermatology 36:4, 431-433
CrossRef33
Charles A. Dinarello. (2011) A clinical perspective of IL-1β as the gatekeeper of inflammation. European Journal of Immunology 41:5, 1203-1217
CrossRef34
J. Schedel, B. Bach, J.B. Kümmerle-Deschner, I. Kötter. (2011) Autoinflammatorische Syndrome/Fiebersyndrome. Der Hautarzt 62:5, 389-402
CrossRef35
Eline A. Dubois, Robert Rissmann, Adam F. Cohen. (2011) Rilonacept and canakinumab. British Journal of Clinical Pharmacology 71:5, 639-641
CrossRef36
C. A. Dinarello. (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:14, 3720-3732
CrossRef37
I. Jéru, S. Amselem. (2011) Inflammasome et interleukine 1. La Revue de Médecine Interne 32:4, 218-224
CrossRef38
, Seza Ozen, Joost Frenkel, Nicola Ruperto, Marco Gattorno. (2011) The Eurofever Project: towards better care for autoinflammatory diseases. European Journal of Pediatrics 170:4, 445-452
CrossRef39
Raphaela Goldbach-Mansky. (2011) Current Status of Understanding the Pathogenesis and Management of Patients With NOMID/CINCA. Current Rheumatology Reports 13:2, 123-131
CrossRef40
L. De Monte, M. Reni, E. Tassi, D. Clavenna, I. Papa, H. Recalde, M. Braga, V. Di Carlo, C. Doglioni, M. P. Protti. (2011) Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. Journal of Experimental Medicine 208:3, 469-478
CrossRef41
Mohamed Lamkanfi. (2011) Emerging inflammasome effector mechanisms. Nature Reviews Immunology 11:3, 213-220
CrossRef42
Helen J. Lachmann, Pierre Quartier, Alexander So, Philip N. Hawkins. (2011) The emerging role of interleukin-1β in autoinflammatory diseases. Arthritis & Rheumatism 63:2, 314-324
CrossRef43
Justin R. Yu, Kieron S. Leslie. (2011) Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response. Current Allergy and Asthma Reports 11:1, 12-20
CrossRef44
Luciana Breda, Marianna Torto, Sara Sanctis, Francesco Chiarelli. (2011) Biologics in children’s autoimmune disorders: efficacy and safety. European Journal of Pediatrics 170:2, 157-167
CrossRef45
Athanassios Kolivras, Anne Theunis, Aline Ferster, Dan Lipsker, Ursula Sass, Anneliese Dussart, Josette André. (2011) Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement. Journal of Cutaneous Pathology 38:2, 202-208
CrossRef46
Ryosuke Osawa, Kristi L. Williams, Nina Singh. (2011) The inflammasome regulatory pathway and infections: Role in pathophysiology and clinical implications. Journal of Infection 62:2, 119-129
CrossRef47
C. A. Dinarello. (2011) Blocking interleukin-1β in acute and chronic autoinflammatory diseases. Journal of Internal Medicine 269:1, 16-28
CrossRef48
Xavier Carné. (2011) Canakinumab, un anticuerpo monoclonal frente a IL-1β, con utilidad potencial en distintos procesos inflamatorios. Medicina Clínica 136, 34-37
CrossRef49
Rieke Alten, Juan Gomez-Reino, Patrick Durez, Andre Beaulieu, Anthony Sebba, Gerhard Krammer, Ralph Preiss, Udayasankar Arulmani, Albert Widmer, Xavier Gitton, Herbert Kellner. (2011) Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study. BMC Musculoskeletal Disorders 12:1, 153
CrossRef50
Norman T. Ilowite, Ronald M. Laxer. 2011. PHARMACOLOGY AND DRUG THERAPY. , 71-126.
CrossRef51
Karyl Barron, Balu Athreya, Daniel Kastner. 2011. PERIODIC FEVER SYNDROMES AND OTHER INHERITED AUTOINFLAMMATORY DISEASES. , 642-660.
CrossRef52
Syuji Takei. (2011) Systemic JIA as an Autoinflammatory Disease. Inflammation and Regeneration 31:1, 52-62
CrossRef53
Juan I. Aróstegui. (2011) Etiopatogenia de los síndromes asociados a criopirina: genética, bases moleculares y el inflamasoma. Medicina Clínica 136, 22-28
CrossRef54
Isabelle Koné-Paut, Helen J Lachmann, Jasmin B Kuemmerle-Deschner, Eric Hachulla, Kieron S Leslie, Richard Mouy, Alberto Ferreira, Karine Lheritier, Neha Patel, Ralph Preiss, Philip N Hawkins, . (2011) Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Research & Therapy 13:6, R202
CrossRef55
Jasmin B Kuemmerle-Deschner, Peter Lohse, Ina Koetter, Guenther E Dannecker, Fabian Reess, Katharina Ummenhofer, Silvia Koch, Nikolay Tzaribachev, Anja Bialkowski, Susanne M Benseler. (2011) NLRP3 E311K mutation in a large family with Muckle-Wells syndrome - description of a heterogeneous phenotype and response to treatment. Arthritis Research & Therapy 13:6, R196
CrossRef56
Megumu K SAITO. (2011) Inflammasomes and related diseases. Japanese Journal of Clinical Immunology 34:1, 20-28
CrossRef57
Jasmin B Kuemmerle-Deschner, Eduardo Ramos, Norbert Blank, Joachim Roesler, Sandra D Felix, Thomas Jung, Kirstin Stricker, Abhijit Chakraborty, Stacey Tannenbaum, Andrew M Wright, Christiane Rordorf. (2011) Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Research & Therapy 13:1, R34
CrossRef58
Megumu K. SAITO. (2011) CAPS : Cryopyrin-associated periodic syndrome. Japanese Journal of Clinical Immunology 34:5, 369-377
CrossRef59
Naomi Schlesinger, Marc De Meulemeester, Andrey Pikhlak, A Eftal Yücel, Dominik Richard, Valda Murphy, Udayasankar Arulmani, Peter Sallstig, Alexander So. (2011) Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study. Arthritis Research & Therapy 13:2, R53
CrossRef60
Santiago Jiménez Treviño, Eduardo Ramos Polo. (2011) Tratamiento de los síndromes periódicos asociados a la criopirina (CAPS). Medicina Clínica 136, 29-33
CrossRef61
Katia Stankovic, Gilles Grateau. (2011) Is there any treatment for inflammatory amyloidosis?. Joint Bone Spine 78:1, 7-9
CrossRef62
Simon M. Mueller, Peter Itin, Peter Haeusermann. (2011) Muckle-Wells Syndrome Effectively Treated with Canakinumab: Is the Recommended Dosing Schedule Mandatory?. Dermatology 223:2, 113-118
CrossRef63
Nicolino Ruperto, Pierre Quartier, Nico Wulffraat, Patricia Woo, Angelo Ravelli, Richard Mouy, Brigitte Bader-Meunier, Sebastiaan J Vastert, Emanuele Noseda, Daniele D'Ambrosio, Jean Lecot, Abhijit Chakraborty, Alberto Martini, Andrea Chioato, . (2011) A phase II study to evaluate dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features. Arthritis & Rheumatismn/a-n/a
CrossRef64
Marco Gattorno, Alberto Martini. (2010) Treatment of autoinflammatory syndromes. Current Opinion in Pediatrics 22:6, 771-778
CrossRef65
Zachary Jacobs, Christina E. Ciaccio. (2010) Periodic Fever Syndromes. Current Allergy and Asthma Reports 10:6, 398-404
CrossRef66
László Maródi, Jean-Laurent Casanova. (2010) Primary immunodeficiencies may reveal potential infectious diseases associated with immune-targeting mAb treatments. Journal of Allergy and Clinical Immunology 126:5, 910-917
CrossRef67
Leigh D Church, Michael F McDermott. (2010) Canakinumab: a human anti-IL-1β monoclonal antibody for the treatment of cryopyrin-associated periodic syndromes. Expert Review of Clinical Immunology 6:6, 831-841
CrossRef68
Alexander So, Marc De Meulemeester, Andrey Pikhlak, A. Eftal Yücel, Dominik Richard, Valda Murphy, Udayasankar Arulmani, Peter Sallstig, Naomi Schlesinger. (2010) Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis & Rheumatism 62:10, 3064-3076
CrossRef69
Mario Abinun. (2010) An overview of infectious complications in children on new biologic response-modifying agents. Pediatric Health 4:5, 509-517
CrossRef70
Aaron L. Nelson, Eugen Dhimolea, Janice M. Reichert. (2010) Development trends for human monoclonal antibody therapeutics. Nature Reviews Drug Discovery 9:10, 767-774
CrossRef71
Tuhina Neogi. (2010) Interleukin-1 antagonism in acute gout: Is targeting a single cytokine the answer?. Arthritis & Rheumatism 62:10, 2845-2849
CrossRef72
Soomin Yoon, Yong-Sung Kim, Hyunbo Shim, Junho Chung. (2010) Current perspectives on therapeutic antibodies. Biotechnology and Bioprocess Engineering 15:5, 709-715
CrossRef73
Prudence Joan Manners, Robin Guttinger. (2010) Fevers and the Rheumatologist. The Indian Journal of Pediatrics 77:10, 1173-1181
CrossRef74
Wen Fury, Adriana H. Tremoulet, Virginia E. Watson, Brookie M. Best, Chisato Shimizu, Jennifer Hamilton, John T. Kanegaye, Yi Wei, Chiayi Kao, Scott Mellis, Calvin Lin, Jane C. Burns. (2010) Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance. Human Immunology 71:9, 865-873
CrossRef75
Manfred Kopf, Martin F. Bachmann, Benjamin J. Marsland. (2010) Averting inflammation by targeting the cytokine environment. Nature Reviews Drug Discovery 9:9, 703-718
CrossRef76
I. Kötter, G. Horneff. (2010) IL-1-Antagonisten. Zeitschrift für Rheumatologie 69:7, 581-593
CrossRef77
K. Krause, F. Degener, S. Altrichter, E. Ardelean, D. Kalogeromitros, M. Magerl, M. Metz, F. Siebenhaar, K. Weller, M. Maurer. (2010) Kälteinduzierte Quaddeln und Angioödeme. Der Hautarzt 61:9, 743-749
CrossRef78
G. Dückers, T. Niehues. (2010) Die Bedeutung von Biologika bei der Therapie der SoJIA (Morbus Still). Zeitschrift für Rheumatologie 69:6, 505-515
CrossRef79
Cailin Henderson, Raphaela Goldbach-Mansky. (2010) Monogenic autoinflammatory diseases: new insights into clinical aspects and pathogenesis. Current Opinion in Rheumatology1
CrossRef80
Loredana Lepore, Giulia Paloni, Roberta Caorsi, Maria Alessio, Donato Rigante, Nicola Ruperto, Marco Cattalini, Alberto Tommasini, Francesco Zulian, Alessando Ventura, Alberto Martini, Marco Gattorno. (2010) Follow-Up and Quality of Life of Patients with Cryopyrin-Associated Periodic Syndromes Treated with Anakinra. The Journal of Pediatrics 157:2, 310-315.e1
CrossRef81
Greta Guarda, Alexander So. (2010) Regulation of inflammasome activity. Immunology 130:3, 329-336
CrossRef82
Hal M. Hoffman, Alan A. Wanderer. (2010) Inflammasome and IL-1β-Mediated Disorders. Current Allergy and Asthma Reports 10:4, 229-235
CrossRef83
Charles A Dinarello, Marc Y Donath, Thomas Mandrup-Poulsen. (2010) Role of IL-1β in type 2 diabetes. Current Opinion in Endocrinology, Diabetes and Obesity1
CrossRef84
Ioannis Mitroulis, Panagiotis Skendros, Konstantinos Ritis. (2010) Targeting IL-1β in disease; the expanding role of NLRP3 inflammasome. European Journal of Internal Medicine 21:3, 157-163
CrossRef85
Tetsuo Kubota, Ryuji Koike. (2010) Cryopyrin-associated periodic syndromes: background and therapeutics. Modern Rheumatology 20:3, 213-221
CrossRef86
Bing Kuang, Lindsay King, Huifen Faye Wang. (2010) Therapeutic monoclonal antibody concentration monitoring: free or total?. Bioanalysis 2:6, 1125-1140
CrossRef87
I. Koné-Paut, I. Marie, V. Magrhraoui, T.-A. Tran. (2010) Traitement des maladies auto-inflammatoires : quelles avancées ?. Archives de Pédiatrie 17:6, 609-610
CrossRef88
Gilles Grateau, Mehmet Tuncay Duruöz. (2010) Autoinflammatory conditions: when to suspect? How to treat?. Best Practice & Research Clinical Rheumatology 24:3, 401-411
CrossRef89
Charles A. Dinarello. (2010) Why not treat human cancer with interleukin-1 blockade?. Cancer and Metastasis Reviews 29:2, 317-329
CrossRef90
Cailin Henderson, Raphaela Goldbach-Mansky. (2010) Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: Finding the right balance in response to danger signals. Clinical Immunology 135:2, 210-222
CrossRef91
Sharon F. Terry. (2010) Accelerate medical breakthroughs by ending disease earmarks. Nature Reviews Genetics 11:5, 310-311
CrossRef92
Bernard Bizzini, Béatrice Drouet, Daniel Zagury, Marc Abitbol, Arsène Burny, Marie-Christophe Boissier. (2010) Kinoids: a family of immunogens for active anticytokine immunotherapy applied to autoimmune diseases and cancer. Immunotherapy 2:3, 347-365
CrossRef93
Angelica Gierut, Harris Perlman, Richard M. Pope. (2010) Innate Immunity and Rheumatoid Arthritis. Rheumatic Disease Clinics of North America 36:2, 271-296
CrossRef94
PJ Lowe. (2010) Applying Physiological and Biochemical Concepts to Optimize Biological Drug Development. Clinical Pharmacology & Therapeutics 87:4, 492-496
CrossRef95
Cem Gabay, Céline Lamacchia, Gaby Palmer. (2010) IL-1 pathways in inflammation and human diseases. Nature Reviews Rheumatology 6:4, 232-241
CrossRef96
Charles A. Dinarello. (2010) Anti-inflammatory Agents: Present and Future. Cell 140:6, 935-950
CrossRef97
Daniel L. Kastner, Ivona Aksentijevich, Raphaela Goldbach-Mansky. (2010) Autoinflammatory Disease Reloaded: A Clinical Perspective. Cell 140:6, 784-790
CrossRef98
Thomas Mandrup-Poulsen, Linda Pickersgill, Marc Yves Donath. (2010) Blockade of interleukin 1 in type 1 diabetes mellitus. Nature Reviews Endocrinology 6:3, 158-166
CrossRef99
Guangxun Meng, Warren Strober. (2010) New insights into the nature of autoinflammatory diseases from mice with Nlrp3 mutations. European Journal of Immunology 40:3, 649-653
CrossRef100
Kate Schroder, Jurg Tschopp. (2010) The Inflammasomes. Cell 140:6, 821-832
CrossRef101
John S Sundy. (2010) Progress in the pharmacotherapy of gout. Current Opinion in Rheumatology 22:2, 188-193
CrossRef102
Charles A. Dinarello. (2010) IL-1: Discoveries, controversies and future directions. European Journal of Immunology 40:3, 599-606
CrossRef103
Argyrios N. Theofilopoulos, Rosana Gonzalez-Quintial, Brian R. Lawson, Yi T. Koh, Michael E. Stern, Dwight H. Kono, Bruce Beutler, Roberto Baccala. (2010) Sensors of the innate immune system: their link to rheumatic diseases. Nature Reviews Rheumatology 6:3, 146-156
CrossRef104
Graham P. Cook, Sinisa Savic, Miriam Wittmann, Michael F. McDermott. (2010) The NLRP3 inflammasome, a target for therapy in diverse disease states. European Journal of Immunology 40:3, 631-634
CrossRef105
Marjorie Makoni, Deepa Mukundan. (2010) Fever. Current Opinion in Pediatrics 22:1, 100-106
CrossRef106
John E. Sims, Dirk E. Smith. (2010) The IL-1 family: regulators of immunity. Nature Reviews Immunology 10:2, 117
CrossRef107
Fabio Martinon. (2010) Mechanisms of uric acid crystal-mediated autoinflammation. Immunological Reviews 233:1, 218-232
CrossRef108
Naotomo Kambe, Yuumi Nakamura, Megumu Saito, Ryuta Nishikomori. (2010) The Inflammasome, an Innate Immunity Guardian, Participates in Skin Urticarial Reactions and Contact Hypersensitivity. Allergology International 59:2, 105-113
CrossRef109
Raphaela Goldbach-Mansky. (2009) Blocking Interleukin-1 in Rheumatic Diseases. Annals of the New York Academy of Sciences 1182:1, 111-123
CrossRef110
Hal M. Hoffman. (2009) Therapy of autoinflammatory syndromes. Journal of Allergy and Clinical Immunology 124:6, 1129-1138
CrossRef111
Raphaela Goldbach-Mansky, Daniel L. Kastner. (2009) Autoinflammation: The prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. Journal of Allergy and Clinical Immunology 124:6, 1141-1149
CrossRef112
O. Blétry, T. Sene, J.-E. Kahn, F. Ackermann, P. Charles, J. Leport, A.-M. Piette. (2009) Quoi de neuf en médecine interne ?. Annales de Dermatologie et de Vénéréologie 136, S417-S425
CrossRef113
A A Wanderer. (2009) Rationale for IL-1β-targeted therapy to minimize hypoxic-ischemic encephalopathy. Journal of Perinatology 29:12, 785-787
CrossRef114
John Orloff, Frank Douglas, Jose Pinheiro, Susan Levinson, Michael Branson, Pravin Chaturvedi, Ene Ette, Paul Gallo, Gigi Hirsch, Cyrus Mehta, Nitin Patel, Sameer Sabir, Stacy Springs, Donald Stanski, Matthias R. Evers, Edd Fleming, Navjot Singh, Tony Tramontin, Howard Golub. (2009) The future of drug development: advancing clinical trial design. Nature Reviews Drug Discovery
CrossRef115
Adam C. Shaw, Raoul C.M. Hennekam. (2009) Interpreting humanity's genes. European Journal of Medical Genetics 52:6, 379-380
CrossRef116
I. Foeldvari, J. Kümmerle- Deschner. (2009) Klinik der autoinflammatorischen Erkrankungen im Kindesalter. Zeitschrift für Rheumatologie 68:9, 726-732
CrossRef117
, B. Manger, M. Gaubitz, H. Michels. (2009) Empfehlungen zur Therapie mit Interleukin-1β-blockierenden Wirkstoffen. Zeitschrift für Rheumatologie 68:9, 766-771
CrossRef118
Thomas Bardin. (2009) Acute inflammatory arthritis: Interleukin-1 blockade: a magic wand for gout?. Nature Reviews Rheumatology 5:11, 594-596
CrossRef119
Sinisa Savic, Michael F. McDermott. (2009) Inflammation: Canakinumab for the cryopyrin-associated periodic syndromes. Nature Reviews Rheumatology 5:10, 529-530
CrossRef120
Cem Gabay, Gaby Palmer. (2009) Genetics: Mutations in the IL1RN locus lead to autoinflammation. Nature Reviews Rheumatology 5:9, 480-482
CrossRef121
(2009) Regulatory watch: IL-1β-targeted antibody approved for rare autoinflammatory disorders. Nature Reviews Drug Discovery 8:8, 605-605
CrossRef122
Dinarello, Charles A., . (2009) Interleukin-1β and the Autoinflammatory Diseases. New England Journal of Medicine 360:23, 2467-2470
Full Text
