Background/Purpose: TNF-receptor associated periodic syndrome (TRAPS) is a rare dominantly inherited periodic fever syndrome due to mutations of the TNFRSF1A gene. It is characterized by recurrent fever attacks associated with rash, musculoskeletal and abdominal pain, conjunctivitis, and periorbital edema. Approximately 10-20% of pts develop renal amyloidosis. The IL-1 receptor antagonist anakinra has been reported to be an efficacious treatment. Canakinumab (CAN) is a fully human monoclonal selective anti-IL-1β antibody with a T_1/2 of ~4 wks. Interim data of open label 4-months CAN therapy and 5-months follow-up in active TRAPS pts is presented.

Methods: 14 adults and 6 children (7 to 78 yrs, median 39 yrs) with active TRAPS entered a 3-part trial: 4 months open-label 150 mg (or 300 mg) CAN every 4 wks followed by up to 5 months treatment withdrawal, and then 24 months open-label CAN. Disease activity was evaluated by a 5-point physician’s global assessment (PGA) score and by CRP and SAA levels. Primary endpoint was complete or almost complete response at Day 15. Complete response was defined as clinical remission (PGA of 0 or 1 [absent or minimal signs/symptoms]) and normal CRP and/or SAA. Almost complete response was defined as clinical remission and elevated but ≥70% reduced from baseline CRP and/or SAA. Quality of life was assessed by the SF-36 in adults. Those without response by Day 8 were eligible for another 150 mg dose and then 300 mg thereafter. Pts were observed after last dose until relapse (5 month max) before restarting CAN.

Results: On Day 8, 16 (80%) achieved complete/almost complete response and 18 (90%) achieved clinical remission. Two pts without clinical remission were dose up-titrated to 300 mg. At Day 15, 19 (95%) achieved complete/almost complete response, including all 4 without it at Day 8. Clinical remission was maintained by all from Day 15 onwards except 1 who relapsed at Day 85, responding to that visit’s CAN dose. Median time to clinical remission was 4 days (95% CI: 3,8). Median baseline CRP (125 mg/L) and SAA (198 mg/L) both reduced to <5 mg/L from Day 15 onwards. All relapsed after stopping CAN at a median 91.5 days. The relapse graded by the PGA was mild in 11, moderate in 7, and severe in 2. Upon redose, 18 regained complete/almost complete response 8-27 days later and 2 relapsed at final visit with no follow-up available for this analysis. Baseline SF-36 components improved after CAN therapy. All pts reported ≥1 adverse event (AE). Infections, mostly of the upper respiratory tract (URI), was the most common (n=15, 75%) AE category. Headache (n=9) followed by abdominal pain (n=7) were the most common specific AEs reported. Two serious AEs, a URI and a TRAPS relapse, were reported. All pts are active in the 24-month open-label period.

Conclusion: Canakinumab produced a rapid and effective clinical and serological benefit which was maintained with continued dosing. Relapse occurred at a median of 3 months after last dose, was usually mild or moderate, and resolved upon re-dosing. Canakinumab demonstrated a favorable safety and tolerability profile in this small study. Data support IL-1β’s pivotal role in TRAPS and further study is needed to better define canakinumab treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-canakinumab-in-patients-with-tnf-receptor-associated-periodic-syndrome/