THU0570 Long-term efficacy and safety of canakinumab in patients with colchicine-resistant fmf (CRFMF), traps and hids/mkd: results from the pivotal phase 3 cluster trial

Abstract

Background: Canakinumab (CAN), a selective, human anti‐interleukin (IL)‐1β mAb, has demonstrated efficacy and safety in patients (pts) with colchicine‐resistant familial Mediterranean fever (crFMF), TNF receptor‐associated periodic syndrome (TRAPS), and hyper‐IgD syndrome (HIDS)/mevalonate kinase deficiency (MKD) in the epoch 2 and 3 (E2 and E3) of the CLUSTER study (NCT02059291).1 2 Objectives: To evaluate the long‐term maintenance of optimal control of disease activity (median of no or 1 flare, and no uptitration) and safety on every 4 weeks (q4w) and every 8 weeks (q8w) dosing regimens of CAN in pts with crFMF, TRAPS or HIDS/MKD from the epoch 4 (E4; 112 weeks) of the CLUSTER study. Methods: The study comprised 4 epochs (E1‐E4). Study design for E2 and E3 have been reported earlier.1 After lead‐in E1, in E2, a 16 wk randomised, doubleblind, placebo (PBO)‐controlled epoch, efficacy of CAN 150/300 mg q4w to induce complete response (absence of flares) was assessed. E3 (24 wks) evaluated whether responders to CAN 150/300 mg q4w in E2 could maintain clinical efficacy on 150/300 mg q8w or PBO. In E4, a 72 wk, open‐label epoch, the longterm maintenance of efficacy and safety of CAN 150/300 mg q4w or q8w in pts with crFMF, TRAPS or HIDS/MKD was evaluated. Pts who did not maintain clinical response on q8w could be uptitrated to 150/300 mg q4w. Safety assessments included adverse events (AEs) and serious AEs. Results: At the end of E4 (Wk 112), a substantial proportion of pts maintained optimal control of disease activity following treatment with 150/300 mg q4w or q8w in all 3 cohorts (figure 1). HIDS/MKD pts more often required uptitration to 300 mg q4w. Majority of pts in all 3 cohorts had 1 or no new flare (crFMF: 96.6%, TRAPS: 94.3%, HIDS/MKD: 83.3%) and physician global assessment <2 (no or minimal disease activity). In all 3 cohorts, the median SAA levels decreased rapidly from baseline and remained suppressed through E4 (crFMF: 618 to 21 mg/L, TRAPS: 243 to 12 mg/L and HIDS/MKD: 2061 to 16 mg/L). No new safety findings were reported in CAN‐treated pts through E4. Conclusions: Epoch 4 of the CLUSTER study demonstrated that optimal control of disease activity in the crFMF, TRAPS and HIDS/MKD patients can be maintained following long‐term treatment with canakinumab 150/300 mg q4w. For all 3 cohorts, patients requiring 150/300 mg q8w in epoch 3 to maintain disease control were less likely to control disease during epoch 4 and therefore a substantial number of these patients were uptitrated to q4w regimen by the end of epoch 4. No new or unexpected safety issues were reported over 112 weeks of canakinumab treatment. (Figure Presented).