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
Authors: F. De Benedetti, J. Frenkel, A. Simon, J. Anton, H. Lachmann, M. Gattorno, S. Ozen, I. Kone-Paut, E. Ben-Chetrit, M.B. Wozniak, J.G. Wang, E. Vritzali
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> 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).<sup>1 2</sup> <h3>Objectives</h3> 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. <h3>Methods</h3> The study comprised 4 epochs (E1-E4). Study design for E2 and E3 have been reported earlier.<sup>1</sup> After lead-in E1, in E2, a 16 wk randomised, double-blind, 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 long-term 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. <h3>Results</h3> 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 &lt;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. <h3>Conclusions</h3> 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. <h3>References</h3> [1] De Benedetti F, et al. Ann Rheum Dis2016;75:615–6. [2] De Benedetti F, et al. Arthritis Rheumatol2016;68(suppl 10). <h3>Disclosure of Interest</h3> F. De Benedetti Grant/research support from: Novartis, Roche, Pfizer, SOBI, AbbVie, Novimmune, BMS, Sanofi, J. Frenkel Grant/research support from: Novartis and SOBI, A. Simon Grant/research support from: Novartis, Xoma/Servier, CSL Behring, Consultant for: Novartis, Takeda, SOBI, Xoma, J. Anton Grant/research support from: Novartis, Consultant for: Novartis, H. Lachmann Consultant for: Novartis, SOBI, Takeda and GSK, Speakers bureau: Novartis and SOBI, M. Gattorno Grant/research support from: Novartis and SOBI, Consultant for: Novartis and SOBI, Speakers bureau: Novartis and SOBI, S. Ozen Speakers bureau: Novartis and SOBI, I. Kone-Paut Grant/research support from: Novartis, SOBI and Roche, Consultant for: Novartis, SOBI, Pfizer, AbbVie and Roche, E. Ben-Chetrit Consultant for: Novartis, M. Wozniak Employee of: Novartis, J. Wang Employee of: Novartis, E. Vritzali Employee of: Novartis