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

Abstract

İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed.Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3-30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m 2 , the median proteinuria decreased from 2390 mg/day (range, 1400-7200) to 890 mg/day (range, 120-2750) (p = 0.008). No serious infections were detected, except in one patient.Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m 2 , but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the longterm effects of these treatments.

Anakinra in familial Mediterranean fever: a profile of its use

“…anti-IL-1 biological treatments) supports the efficacy results observed during the pivotal phase 3 trial (Table 3) [14][15][16][17][18][19]. Decreases in FMF attack frequency [14][15][16][17][18], CRP levels [14,16,17,19], and/or reduction of disease activity [15][16][17]19] were reported with anti-IL-1 treatment across six studies that each included ≥ 20 patients treated with anakinra (Table 3). Improvements were also reported across all 36-item short form survey (SF-36) QoL domains following anti-IL-1 treatment in one study (Table 3) [18].…”

“…Real-world experience with anakinra and canakinumab (i.e. anti-IL-1 biological treatments) supports the efficacy results observed during the pivotal phase 3 trial (Table 3) [14][15][16][17][18][19]. Decreases in FMF attack frequency [14][15][16][17][18], CRP levels [14,16,17,19], and/or reduction of disease activity [15][16][17]19] were reported with anti-IL-1 treatment across six studies that each included ≥ 20 patients treated with anakinra (Table 3).…”

Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment

“…Anakinra is a recombinant IL-1R antagonist (rHIL-1Ra) and is the first IL-1 blocking biologic agent produced. Anakinra blocks the binding of both IL-1α and IL-1β to IL-1R, thereby inhibits the proinflammatory effects of IL-1 [59]. Anakinra was found to be beneficial in patients with severe sepsis without significant adverse effects based upon the data of phase 3 randomized clinical trial [60].…”

“…Hepatic disease does not require dose adjustment. Unlike TCZ, anakinra does not inhibit CRP synthesis directly; therefore, serum CRP levels can be used to follow up systemic acute phase response [59]. Another molecule produced for IL-blockage is canakinumab, which is a high affinity, fully humanized, monoclonal anti-IL-1β antibody with IgG1/κ isotype.…”

“…Following SC injection of 150 mg, peak serum concentration is achieved in 7 days. The recommended dose interval is every 2 months [59]. The third molecule developed for IL-1 blockade is Rilonacept, which is a recombinant soluble IL-1 receptor.…”