Abstract
Background:Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with mutations in theMEFVgene. Colchicine is the cornerstone of current therapy for FMF; however, a subset of patients are resistant or intolerant to it. Previously published results from the CLUSTER trial [NCT02059291] demonstrated that canakinumab, a fully human anti-interleukin-1β monoclonal antibody, was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever (crFMF).1Objectives:To evaluate the long-term efficacy and safety of canakinumab to treat patients with crFMF during Epoch 4 of the CLUSTER study.Methods:Patients with active crFMF (baseline flare) were enrolled in the CLUSTER study. During Epoch 4 (weeks 40 to 113), patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks (q4w or q8w). Patients started Epoch 4 on the same regimen that they were receiving at the end of Epoch 3, and stepwise up-titration of canakinumab was allowed in patients who experienced a flare, to a maximum dose of 300 mg q4w. We evaluated disease activity every 8 weeks using the physician global assessment of disease activity (PGA), counting the number of flares (defined as PGA ≥2 and CRP >30 mg/L), and measuring serum concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was assessed by the determination and classification of adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of canakinumab lower than 2700 mg, or equal or higher than 2700 mg.Results:Of the 61 patients with active crFMF who started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one single flare, as compared with a median of 17.5 flares per year reported at baseline. The incidence of flares was similar in the two cumulative dose groups. PGA scores indicated no disease activity for the majority of patients throughout the study, in both cumulative dose groups. 23/57 (40%) of patients remained in the lower dosing group (150 mg q8w) until study end, whereas 9/57 (16%) required the highest dose allowed (300 mg q4w). Patients with higher body weight had an increased probability to require up-titration of canakinumab to control disease activity. Median CRP concentrations were lower than 10 mg/L at every time point in both cumulative dose groups, while median SAA concentrations remained in the 16-70 mg/L range, and were higher in the group receiving ≥2700 mg canakinumab (Figure 1). No opportunistic infections, renal disease caused by amyloidosis, new or unexpected AEs were reported.Figure 1.SAA and CRP blood levels in Epoch 4 of the CLUSTER study, in two subgroups of patients treated with a cumulative dose of canakinumab <2700 mg or ≥2700 mgConclusion:Patients with crFMF treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety signals reported.
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