Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever

Abstract

IntroductionThis open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients.MethodPatients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36.ResultsThirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials.ConclusionCanakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab’s potential in the treatment of patients with colchicine resistant FMF.Trial registrationClinicalTrials.gov NCT01088880. Registered 16 March 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0765-4) contains supplementary material, which is available to authorized users.

<p>The Efficacy, Safety and Tolerability of Canakinumab in the Treatment of Familial Mediterranean Fever: A Systematic Review of the Literature</p>

“…Data on previous immunosuppressive therapy were available for 100 patients. [13][14][15][16][17][18][19][20][21] Forty-four patients used Anakinra prior to initiation of Canakinumab therapy. Of them, 26 had an intolerance to Anakinra and in 16 patients Anakinra was ineffective in preventing attacks.…”

“…13,17,18,[20][21][22][23][24][25][26][27][28] In case of inadequate disease control, an increase in dose to 3-4mg/kg in those below 40kg or 300mg in those over was used in 8 studies. 10,14,15,19,23,[29][30][31] In 8 studies, 10,19,22,[25][26][27][28]31 Canakinumab was given at 4-weekly intervals, in 3 studies 18,21,24 it was given at 8-weekly intervals, whereas the remaining studies had dosing frequencies tailored to clinical needs and/or protocols, with the medication being given every 4, 6 or 8 weeks.…”

“…The articles by Gul et al and Babaoglu et al reported on one Canakinumab-exposed pregnancy each. 14,19 The medication was discontinued in the peri-conception period and at 8 weeks' gestation, respectively. There were no signs of congenital malformations or intra-uterine growth retardation, both infants were carried to term and no developmental abnormalities were reported.…”

Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management

“…Eighteen reports were on treatment with anakinra (103–120), four on canakinumab (100, 101, 121, 122), four on patients treated with either anakinra or canakinumab (123–126), and the only placebo-controlled prospective trial was on treatment with rilonacept (102). A complete response to therapy was reported in 76.5% of patients on anakinra, and 67.5% of patients on canakinumab treatment (99).…”

Familial Mediterranean fever

“…Following the concept of FMF as an AID, in which hypersecretion of the proinflammatory cytokine IL-1b, IL-1 antagonists have been proposed as a possible treatment for colchicine-resistant FMF patients by IL-1 blockage [50]. Open-label pilot studies investigated the efficacy of canakinumab in a group of nine adult colchicine-resistant FMF patients [52], and later in seven children [53 && ], showing promising results. Canakinumab is a high affinity, fully human monoclonal anti-IL-1b antibody with a half-life of 4 weeks that binds human IL-1b and blocks its interaction with its receptors, thus functionally neutralizing cytokine bioactivity without preventing IL-1b binding to the natural inhibitor.…”