Treatment of colchicine-resistant familial Mediterranean fever: a retrospective cohort study

Lifelong administration of colchicine is the mainstay of treatment for familial Mediterranean fever (FMF), whereas canakinumab, a monoclonal antibody that blocks the effects of interleukin (IL)-1β, can be used in case of colchicine resistance or its poor tolerability.

Aim

To evaluate the effectiveness of canakinumab in the treatment of FMF patients with colchicine resistance or intolerance.

Material and methods

We followed 23 patients with FMF who received canakinumab at a starting dose of 150 mg every 4 or 8 weeks. In 20 patients, the indication for the use of canakinumab was colchicine resistance, that is, persistence of FMF symptoms and elevated C-reactive protein (CRP) levels between attacks. Treatment response criteria included reduction in frequency, severity, or complete cessation of FMF attacks and reduction in CRP levels.

Results

The median duration of canakinumab therapy was 23 months (7-47). In 18 (78.2%) of 23 patients, canakinumab was used in combination with colchicine at a dose of 0.5-2 mg/day. In the whole population, median CRP decreased from 35 (20; 67) to 4 (3; 12) mg/L. Remission of FMF, characterized by alleviation of disease attacks and normalization of CRP level, was achieved in 15 (65.2%) cases, whereas in 8 (34.8%) patients there were significant clinical improvement and reduction in CRP level, although the latter did not reach the normal values. In 8 of 14 patients, canakinumab therapy resulted in relief of nephrotic syndrome. Treatment with canakinumab was more effective at a dose of 150 mg every 4 weeks.

Conclusion

Laboratory disease activity should be carefully monitored to assess colchicine resistance in FMF. The use of the long-acting IL-1 inhibitor canakinumab is effective and safe for colchicine-resistant FMF.

Key words

familial Mediterranean fever, autoinflammation, colchicine resistance, colchicine intolerance, IL-1 inhibitors, canakinumab.