Background/Purpose:

Treatment with canakinumab (CAN), a selective, human anti-IL-1β monoclonal antibody, has shown sustained therapeutic effect along with corticosteroid dose reduction/discontinuation in patients with systemic juvenile idiopathic arthritis (SJIA), in a long-term extension study (NCT00891046).¹ Herein, we report the efficacy and safety results from a study evaluating 2 different CAN tapering regimens in SJIA patients who were in clinical remission (NCT02296424).

Methods:

This Phase 3b/4 study had two parts. In Part I, 182 patients with inactive disease from the extension study¹ (cohort 1) and CAN-naïve patients (cohort 2) with active disease were administered subcutaneous CAN 4 mg/kg q4w. Per protocol titration off corticosteroids and/or methotrexate was attempted during Part I. Eligible patients (inactive disease for 24 consecutive weeks and being corticosteroid- and methotrexate-free for at least 4 weeks) advanced to Part II. Patients were randomized to either a 3-step CAN dose reduction regimen (2mg/kg/q4w, followed by tapering to 1 mg/kg/q4w and then discontinuation) or dose interval prolongation regimen (4mg/kg q8w, followed by tapering to 4 mg/kg/q12w and then discontinuation); patients advanced to the next tapering step if inactive disease was maintained for 24 weeks. The primary objective was to evaluate if at least 40% of patients were able to maintain inactive disease status for at least 24 consecutive weeks on either 2mg/kg q4w or 4mg/kg q8w.

Results:

In Part II, a total of 75 patients were randomized to a dose reduction (n=38) or dose interval prolongation (n=37) CAN tapering regimen. The proportion of patients who maintained inactive disease for 24 consecutive weeks exceeded the predefined threshold of 40% for Step 1 of: the reduced CAN dose (71%; 2 mg/kg q4w) and prolonged dose interval (84%; 4 mg/kg q8w) treatment arms. A total of 68% (26/38) and 79% (30/37) of the dose reduction and interval prolongation arms, respectively were successful in Step 2, while only 33% (25/75) of patients successfully discontinued CAN and maintained inactive disease for 24 consecutive weeks. Adverse events (AEs) and serious AEs observed within the 2 treatment cohorts and across Parts I and II were similar without any specific pattern or relationship to patients’ disease status at baseline or treatment regimen. The most frequent AEs were common infections such as nasopharyngitis, upper respiratory tract infection, and pharyngitis followed by SJIA-related events such as rash, pyrexia and arthralgia. Clinical laboratory abnormalities were consistent with expected findings in patients with active SJIA and the known safety profile of CAN.

Conclusion:

SJIA patients who are able to maintain inactive disease status on CAN monotherapy can successfully taper CAN by either reducing the dose or prolonging the dosing interval. However, only a minority of patients successfully discontinued CAN treatment for 24 weeks. The safety profile for both CAN titration regimens was similar and consistent with other CAN SJIA studies; no new signals were identified.

Reference: 1. Brunner et al. Arthritis Rheumatol.2016; 68 (S10).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/canakinumab-on-a-reduced-dose-or-a-prolonged-dose-interval-without-concomitant-corticosteroids-and-methotrexate-maintains-efficacy-in-systemic-juvenile-idiopathic-arthritis-patients-in-clinical-remi/