Background Systemic juvenile idiopathic arthritis (SJIA) is a rare autoinflammatory disease. Phase 3 data showed canakinumab (CAN), a fully human selective anti-IL-1β monoclonal antibody, provided robust initial adapted ACRpedi response in SJIA patients (pts) following a single dose.
Objectives Demonstrate sustained efficacy of CAN in the maintenance of adapted ACRpedi response.
Methods This was a two-part Phase 3 study in SJIA pts (2-20 yrs; CAN naïve or rolled-over from earlier studies). Part 1 (P1), an open label, active treatment maximum 33 wk long period (including a max 20 wk corticosteroid [CS] dose reduction subpart) was followed by Part 2 (P2), a randomized, DB, placebo-controlled, event-driven period. In P1, pts received CAN sc (4mg/kg to 300mg max) every 4 wks. Primary endpoint for P1 was the proportion of pts on CS at study entry who were able to taper it. We present data for the secondary endpoints: maintenance of adapted ACRpedi30/50/70/90/100 criteria, number of active joints and physician’s global assessment of disease activity (PGDA; 0-100 mm VAS) during P1. ACR response was assessed at Days 15, 29 and every 4 weeks thereafter. PGDA and number of active joints were assessed at these same visits and at Baseline (BL) and Day 3.
Results 177 pts (128 on CS; 49 steroid-free) entered P1, of which 100 pts (CAN, n=50; placebo, n=50) entered P2; most of the 77 pts who did not enter P2 were eligible (>ACR30 at Day 15) to enter an open-label extension study directly when they discontinued. Of 92 pts attempting CS taper according to pre-specified criteria, 57 (62%) were successful, representing 44.5% (57/128; p<0.0001) of all pts who entered the study on a CS. 42 of the 92 (46%) who attempted a CS reduction and 42/128 (33%) of those entered study on a CS completely discontinued the CS. At Days 15 and 57, 84% and 94% were responders (≥ACR30), 59% and 78% had a minimum ACR70, and 17% and 39% had an ACR100, respectively. During the CS tapering period of P1, the proportion of pts in each ACR category remained stable except for ACR100 category which decreased from 30% at the start to 16% at the end of the CS taper period. At the end of P1: 76% had a minimum ACR30, 63% had a minimum ACR70 and 34% had an ACR100. Median PGDA was 70mm at BL and improved to 30mm at the first post-BL visit on Day 3. It decreased to 5mm on Day 85, the start of the steroid tapering period, to 3mm (96% improvement) at the end of the taper period on Day 197 and was 7mm at the end of P1. Median no. of active joints decreased from 10 at BL to 2 at Day 15 (-75%) and 1 (-93%) at Day 57. The median no. active joints continued to remain low during the steroid taper period (1 at Day 85; 2 at Day 169). At the end of P1, the median active joint count was 1. In P1, 78% of pts had at least 1 AE, the most common being an infection, mostly involving the upper respiratory tract. SAEs were reported in 14 pts, mostly due to infection (7pts) and MAS (4pts). 1 fatal MAS case occurred in 1 pts on CAN in P1.
Conclusions CAN allowed for successful steroid tapering with sustained maintenance of high adapted ACRpedi response while demonstrating an acceptable safety and tolerability profile in pts with active SJIA.
Disclosure of Interest P. Quartier Grant/Research support from: Novartis, J. Anton Grant/Research support from: Novartis, Pfizer, Consultant for: Novartis, Roche, Paid Instructor for: Novartis, Roche, Abbot, Speakers Bureau: Novartis, Pfizer, Abbot, SOBI, J. Barash Grant/Research support from: Novartis, R. Berner Grant/Research support from: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, D. Kim Shareholder of: Novartis, Employee of: Novartis, N. Wulffraat: None Declared
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