Background/Purpose:

Schnitzler’s syndrome (SchS) is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy in combination with episodes of fever, arthralgia, fatigue, and bone and muscle pain. Anti-IL-1 targeting therapies in small patient numbers including an open-label study with canakinumab (CAN) showed to be effective in reducing the clinical symptoms of SchS. 

Methods:

The current placebo-controlled study was designed to assess the effects of the selective anti-IL-1ß humanized monoclonal antibody CAN on the clinical signs and symptoms of SchS in a larger patient cohort. A total of 20 patients with active disease enrolled in this multi-center trial. After a baseline period of up to 4 weeks, patients were randomized to receive a single CAN 150mg or placebo s.c. injection (day 0) and were evaluated for treatment response at day 7. This initial study period was followed by a 16-week open label phase with CAN injections upon confirmed relapse of clinical symptoms. Efficacy was determined by changes in the physician’s global assessment (PGA; range 0-20), a combined symptom score which includes 5 key symptoms of SchS (urticarial rash, fever, fatigue, arthralgia and myalgia), measurement of the inflammation markers C-reactive protein (CRP) and serum amyloid A (SAA) as well as changes in quality of life assessment (SF-36).

Results:

CAN was highly effective (P=0.001) in reducing median PGA total scores (14.0 to 2.0) within 7 days after first administration as compared to placebo treatment (15.0 to 13.0) in SchS patients. Also, significant (P<0.0001 – P<0.05) improvements were observed for each key symptom score. Median CRP reduced from 9.3mg/dL at baseline to 0.6mg/dL at day 7 in the CAN group vs increase from 3.0mg/dL to 5.0mg/dL for the placebo group. Similarly, median SAA levels reduced from 428mg/L to to 13mg/L for the CAN group vs increase from 160mg/L to 205mg/L for the placebo group.  The median change from baseline between treatment groups for CRP (p=0.004) and SAA (p=0.002) was significant.  Likewise, quality of life as measured by SF-36 significantly improved (P=0.001) for the CAN vs placebo groups at day 7. These improvements were maintained during the 16-week open label phase of the study. A total of 22 adverse events (AEs) were reported during the study including 3 serious AEs (2 hypertensive episodes in 1 patient and severe lumbago in another patient).

Conclusion:

In this 4-month study, CAN s.c. injections significantly improved the clinical signs and symptoms of SchS, reduced inflammation markers, and enhanced quality of life. CAN treatment may be considered a promising therapeutic option in these patients.

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« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/canakinumab-treatment-in-schnitzlers-syndrome-a-multi-center-randomized-placebo-controlled-4-month-study/