Background/Purpose: Interleukin-1β (IL-1β) is a key cytokine in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA). Canakinumab (CAN), a selective fully human anti-IL-1β monoclonal antibody, is efficacious in the treatment of SJIA.¹ Limitation of use of corticosteroids (CS), a current mainstay of therapy for SJIA, is desirable given their well-known long-term side effects. The present study was aimed to determine patient characteristics that are associated with CS discontinuation with CAN therapy and provide details for the CS-reducing potential of CAN in SJIA.

Methods: As part of the phase 3 program of CAN, patients aged 2-19 years with active SJIA plus fever received CAN (4 mg/kg; max:300 mg) every 4 weeks subcutaneously.¹ During a CS-tapering phase of up to 20 weeks, CS were reduced as per pre-specified rules, provided patients achieved an adapted JIA ACR50.¹ Here, we present patient baseline features pertinent to CS tapering successes, defined as at least a 25% reduction of the baseline CS dose (primary endpoint), reaching a low-dose CS requirement, i.e. ≤0.2 mg/kg/day and CS-free status (secondary endpoints).

Results: At baseline, 128/177 patients used daily CS [median (range) mg/kg dose: 0.27 (0.02 – 1.00)] of whom 72% (92/128) entered the CS-tapering phase. Upon completion of the CS-tapering phase 57/128 patients (44.5%; p<0.0001; 90%CI: 37.1-52.2) qualified as CS-tapering successes (primary endpoint). Of note, the majority of the patients either discontinued CS entirely (n=42) or required only low-dose CS (n=24) (secondary endpoints). Compared to patients still on CS (n=86), the 42 patients achieving CS-free status [values are all medians (1^st, 3^rd quartile)] had fewer joints with active arthritis [15 (8, 29) vs. 7 (3, 13)], fewer joints with limitation on motion [14 (7, 33) vs. 5.5 (2, 12)] at baseline. The groups were no different in terms of gender, race, SJIA duration, CRP, number of flares in 6-months period preceding baseline, or specific types of systemic features (hepatosplenomegaly, lymphadenopathy or serositis). Additional associations of CS-free status, initial CAN response, and select laboratory baseline features will be provided.  

Conclusion:

Findings of the Phase III program of CAN in SJIA suggest that CS requirements are substantially reduced after as few as 4 injections. The CS-sparing potential of CAN appears to be great as CS were discontinued entirely in a sizeable proportion of patients with active SJIA in this study.

 

References: 1. Ruperto N. et al. N Engl J Med 2012;367:2396-406.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/baseline-characteristics-of-patients-with-active-systemic-jia-on-canakinumab-therapy-successfully-discontinuing-corticosteroids-secondary-analyses-from-a-pivotal-phase-3-study/