IL1-blocking therapy in colchicine-resistant familial Mediterranean fever

Abstract

ObjectiveApproximately 10%–20% of patients with familial Mediterranean fever (FMF) show an inadequate response to colchicine. In our cohort study, patients with FMF with or without amyloidosis and with an inadequate response to colchicine were treated with anakinra or canakinumab.MethodsClinical and laboratory parameters, Mediterranean fever (MEFV) mutations, and patient-reported outcomes were analyzed in 31 patients treated with anakinra or canakinumab.ResultsIn a cohort of 250 adult patients with FMF, 31 patients were treated with anakinra (n=29) or canakinumab (n=2). The median Pras FMF severity score was 8 (range, 5–14) and correlated with the presence of high-penetrance MEFV mutations (p.Met-694-Val or p.Met-680-Ile). The FMF severity score was 11 in patients with two high-penetrance MEFV mutations (68%), 9 in those with a single high-penetrance MEFV mutation (19%), and 7.5 in those without high-penetrance MEFV mutations (13%, p=0.2). FMF-related amyloid A amyloidosis was diagnosed in 12 (39%) patients. Anakinra was used daily in 20 patients, thrice a week in 7, and upon demand during attacks in 2. Two patients were treated with canakinumab. IL-1-blocking treatment showed a rapid (2±3 days) and persistent suppression of FMF symptoms and inflammatory parameters. The frequency of FMF attacks was significantly reduced (p<0.003). Both patient- and physician-reported FMF activity significantly improved (p<0.0001).ConclusionIL-1-blocking therapy was well tolerated over a median period of 2 years and reduced the frequency of FMF attacks in patients with colchicine-resistant FMF.

Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever

“…Moreover, the serum acute phase reactants of these patients returned to normal levels [10]. Kohler et al achieved a 90% FMF-50 score with IL-1blocking therapy in 31 FMF patients [11]. In our study, we achieved a 96% FMF-50 response rates for the anti-IL-1 treatments, which is similar to previous studies.…”

Effect of anti‐interleukin‐1 treatment on quality of life in children with colchicine‐resistant familial Mediterranean fever: A single‐center experience

“…Local reactions with anakinra are reported in 25% of patients, which were transient and tolerable. In this study, the quality of life in patients treated with canakinumab was better than anakinra due to daily injection 23. In our study, local reactions with anakinra and headache were more frequent, whereas these side effects were not observed in canakinumab.…”

“…Recently, studies have shown that anti-IL-1 treatment is effective and safe in children with FMF. 22 Köhler et al 23…”

“…Recently, studies have shown that anti‐IL‐1 treatment is effective and safe in children with FMF 22 . Köhler et al 23 demonstrated that anakinra and canakinumab treatment were effective and safe in colchicine‐resistant FMF patients, and significant improvements in the modified FMF 50 score were demonstrated. Both agents have been shown to reduce acute‐phase reactants and attack frequency in colchicine‐resistant FMF.…”

The Use of Interleukine-1 Inhibitors in Familial Mediterranean Fever Patients: A Narrative Review

“…Significant reasons to prescribe anakinra rather than canakinumab are the price and/or reimbursement conditions of the drugs, explaining probably partially why the experience in the literature with anakinra is more substantial than with canakinumab. By analyzing studies in which patients have switched from one treatment to another, it seems that the main reason for switching is the ease of administration of canakinumab and/or the loss of compliance to anakinra after longer periods of use (36,43,56,61,64,66,72). A second reason for switching from anakinra to canakinumab is the occurrence of injection site reactions or other side effects with anakinra (such as urticaria or the rise of liver enzymes) which seem less prominent when taking canakinumab (40,42,43).…”