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Previous Volume 360:2416-2425 June 4, 2009 Number 23 Next

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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 [ClinicalTrials.gov] .)

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{at}medsch.ucl.ac.uk.

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