Use of canakinumab in the cryopyrin-associated periodic syndrome.
Author(s): Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier
P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group.
Collaborators: Madhoo S, Berthelot JM, Jorgensen C, Morell-Dubois S, Mouy R,
Marie I, Lacassagne S, Chaturvedi R, Vargas C, Block JA, Smith J.
Affiliation(s): University College London Medical School, London, United Kingdom.
h.lachmann@medsch.ucl.ac.uk
Publication date & source: 2009, N Engl J Med. , 360(23):2416-25
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-1beta 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.)
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