Anti-IL-1 Agents May Be Effective in the Treatment of Familial Mediterranean Fever in Patients With Colchicine Resistance/Intolerance

Woman looking at thermometer
Ill woman looking at thermometer at home.
Investigators assessed the effectiveness of anakinra and canakinumab in patients with familial Mediterranean fever who were resistant/intolerant to colchicine or who had complications with amyloidosis.

Anti-interleukin-1 (anti-IL-1) agents anakinra and canakinumab may be safe and effective in the treatment of familial Mediterranean fever (FMF), according to study results published in Advances in Rheumatology. Researchers showed that these anti-IL-1 agents were effective in reducing proteinuria but less effective in cases with FMF associated with arthritis and sacroiliitis.

Colchicine is typically the primary treatment for FMF attacks and amyloidosis; however, 5% to 15% of patients become resistant/unresponsive to colchicine for whom biologic agents including anti-IL-1 are indicated. In this study, the researchers investigated the safety and efficacy of anakinra and canakinumab in patients with colchicine-resistant FMF.

Investigators enrolled 65 patients (median age, 32 years [range, 17-60 years]; 50.8% men) from the Sivas Cumhuriyet University between January 2014 and March 2019 who were diagnosed with FMF, according to Tel-Hashomer criteria, and had colchicine resistance/intolerance. Researchers collected data from laboratory values, clinical features, and disease activities, and analyzed the information every 3 months. More than half (63.1%) of the patients received anakinra (100 mg/d subcutaneous) and 36.9% of the patients received canakinumab (150 mg/8 week subcutaneous). Median duration of the anti-IL-1 agents was 6 and 8 months for anakinra and canakinumab, respectively.

Researchers found a statistically significant improvement in the visual analog scale, erythrocyte sedimentation rate, C-reactive protein, and attack duration with anti-IL-1 treatment. A total of 96.9% patients (n=63) achieved FMF-50 score response for the anti-IL-1 treatments. Anti-IL-1 agents significantly decreased proteinuria in patients with glomerular filtration rate ≥60 mL/min/m2; the median proteinuria decreased from 2390 mg/d (range, 1400-7200 mg/d) to 890 mg/d (range, 120-2750 mg/d; P =.008). For the group with glomerular filtration rate <60 mL/min/m2, the median proteinuria decreased from 4472 mg/d (range, 1950-11,200 mg/d) to 3960 mg/d (range, 2050-12,200 mg/d), although the difference was not statistically significant (P =.345). In terms of safety issues, there were serious infections or tuberculosis or malignancy, except in 1 patient.

Related Articles

Study limitations included the small sample size, lack of a randomized controlled trial, and the fact that there was no adjustment for confounding factors such as blood pressure, use of angiotensin receptor blocker drugs, and diet.

“[Randomized controlled trials] should be conducted to demonstrate the efficiency of the treatment in these clinical situations. Further studies are needed to determine the safety and long-term side effects of anti-IL-1 therapies,” the researchers concluded.


Sahin A, Derin ME, Albayrak F, Karakas B, Karagoz Y. Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever. Adv Rheumatol. 2020;60(1):12.