Background Schnitzler syndrome is a chronic disabling autoinflammatory disorder, characterized by chronic urticaria, paraproteinemia and systemic inflammation. The interleukin-1 receptor antagonist (IL-1Ra) anakinra has been reported as very effective, but requires daily injection because of its short half-life, and is associated with injection site reactions. Canakinumab is a fully human monoclonal selective anti-IL-1β antibody with a half-life of ∼28-30 days in adults with CAPS.1
Objectives To investigate the efficacy, safety and drug dynamics of canakinumab in Schnitzler syndrome patients.
Methods Eight adults with active classical or variant type Schnitzler syndrome who previously responded to anakinra, entered a 9-month trial comprising 6 months of open-label 150mg canakinumab sc injections every 4 weeks and 3 months follow-up. Patients were evaluated clinically using 5-point Physician and Patient Global Assessment of disease activity scales and serologically by C-reactive protein (CRP) levels. The primary endpoint was the percentage of patients with complete or clinical remission at Day 14. Complete remission was defined as clinical remission with normal CRP and clinical remission was defined as having absent or minimal disease activity and >70% improved, but still elevated, CRP. Canakinumab disposition was characterized using pharmacokinetic modeling methodologies from blood samples collected throughout the trial.
Results Upon discontinuation of anakinra, all patients developed active Schnitzler syndrome characterized by general malaise, non-pruritic to burning urticaria, fever and arthralgia or arthritis. In all patients, complete or clinical remission was achieved at Day 14. Mean CRP concentrations decreased from 162 at baseline to <10 mg/L on Day 14 and remained low or undetectable afterwards. One patient discontinued on Day 39 because of return of symptoms while all other patients remained in complete or clinical remission for the remainder of the 6-month treatment period. Relapse in the follow-up period occurred in 4 patients and ranged between 1.5 and 3.5 months after the last canakinumab dose. For 2 patients, remission is continuing >6 months post-study to date. Five patients reported at least 1 adverse event with only rhinitis, pharyngitis and vertigo reported in >1 patient (N=2). One mild local site reaction was reported and 1 patient died in a traffic accident (Day 185). Preliminary analysis of pharmacokinetics results are comparable to the results obtained in previous trials in CAPS patients.
Conclusions In this 9-month study, monthly 150mg canakinumab injection was an effective and well-tolerated treatment in Schnitzler syndrome. Adverse events were manageable. Based on preliminary modeling, PK of canakinumab in patients with Schnitzler syndrome was similar to that in CAPS patients. Data suggest that IL-1β plays a pivotal role in this disease and further study is needed to better define canakinumab treatment.
Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 2009; 360(23):2416-2425.
Disclosure of Interest H. De Koning Grant/Research support from: Novartis, J. Schalkwijk: None Declared, J. van der Ven-Jongekrijg: None Declared, M. Stoffels: None Declared, J. van der Meer Consultant for: Novartis, A. Simon Grant/Research support from: Novartis, Consultant for: Novartis
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