Effectiveness of Canakinumab in Colchicine- and Anakinra-Resistant or -Intolerant Adult Familial Mediterranean Fever Patients

Abstract

Objective We aimed to present our single-center real-life experience of canakinumab use in adult patients with familial Mediterranean fever (FMF). Methods Data were derived from the Gazi FMF cohort, which was established in 2010. From that year, all patients with FMF were registered. The impact of FMF on their lives was tracked by either an FMF diary or mobile phone application (FMF-AIDD, free to download in App Store and Google Play). The records of patients who were treated with canakinumab were reviewed. Results Twenty-three adult patients with FMF (65% female) were enrolled in this study. The median age was 32 years (min–max, 24–58 years), and the disease duration was 26 years (14–59 years). A total of 86% of patients harbored homozygous or compound heterozygous exon 10 MEFV mutations. Indications for interleukin 1 inhibitor use were colchicine resistance (n = 12) or intolerance (n = 2), amyloidosis (n = 7), and chronic manifestations of the disease (n = 2). All patients used anakinra before. The median duration of canakinumab use was 7 months (min–max, 1–44 months). Pre- and post-canakinumab periods were compared. Attack severity, duration, frequency, C-reactive protein level, and erythrocyte sedimentation rate were significantly improved (p ≤ 0.01), whereas serum creatinine and alanine aminotransferase levels remained the same (p = 0.27 and p = 0.74, respectively). Canakinumab achieved complete disease remission in 14 patients (60%). Canakinumab was discontinued in 7 patients. The reasons for discontinuation were pregnancy (n = 2), dominance of axial spondyloarthropathy (n = 2), inflammatory bowel disease, patient's refusal, and weight gain. Conclusions Canakinumab is effective in the prevention of FMF bouts without severe adverse effects. Treatment with canakinumab in an individualized dose and interval may be a reasonable choice for colchicine- and anakinra-resistant or -intolerant adult patients with FMF and those with chronic manifestations of disease.

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

“…Anakinra seems to be more often responsible for cases of leucopenia (28,37,40,62,66), whereas headache (considered occasionally to be severe) seems to be observed more frequently with canakinumab (25,38,48,55,57).…”

<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.…”

“…Information about the presence of renal or systemic amyloidosis could be obtained from 121 patients in 11 of the assessed studies. 14,17,24,[26][27][28] Twenty-four patients had type AA amyloidosis at the start of treatment. Of those, six had Notes: Data are provided as mean ± standard deviation or median and range.…”