Anti-IL-1 Agents Improve Growth in Children With Familial Mediterranean Fever

Anti-IL-1 agents were found to be safe and effective, and improve long-term growth, in children with colchicine-resistant Familial Mediterranean Fever.

Anti-interleukin (IL)-1 agents were found to improve growth in colchicine-resistant Familial Mediterranean Fever (FMF) among children.

FMF is the most common monogenic autoinflammatory disease that results in recurrent inflammatory attacks. FMF is thought to be caused by a gain of function mutation in MEFV innate immunity regulator, pyrin (MEFV). Anti-IL-1 agents have been used to treat FMF but long-term outcomes for pediatric patients have not been fully elucidated.

Data from pediatric patients who received anti-IL-1 agents for FMF between 2006 and 2022 were evaluated for long-term outcomes.

A complete response to treatment was defined as normal levels of inflammatory markers and a partial response was defined as reduced severity and frequency of inflammatory attacks without a complete response.

Of 646 pediatric patients with FMF, 22 (3.4%) required treatment with anti-IL-1 agents. Patients were diagnosed with FMF at an average age of 3.68±2.04 years and 63.6% were girls. Anti-IL-1 therapy was initiated 9.17±3.94 years after diagnosis. A total of 54.5% of patients had moderate disease.

The majority of patients received canakinumab (90.9%); 36% received anakinra. Patients received anti-IL-1 treatment due to colchicine resistance (66.6%) or intolerance (52.3%).

…we suggest considering early treatment when needed, especially for those who harbor the M694V homozygous mutation.

After an average of 3.05±1.75 years of anti-IL-1 treatment, 80% had a complete response and low rates of adverse effects.

Compared with baseline, both body weight (mean, 39.1% vs 29.5%; P =.043) and height (mean, 19.6% vs 30.8%; P =.007) increased significantly after treatment initiation, respectively.

During the 771 patient-months of anti-IL-1 treatment, 1 patient reported an injection site reaction and 2 had abdominal pain.

The researchers noted that compared with pediatric patients with FMF who received other treatments (n=517), those who received anti-IL-1 agents had a higher proportion of homozygosityfor MEFV p.M694V (30.5% vs 95.2%; P <.0001) and lesser heterozygosity (33.2% vs 0%; P =.0004) or compound heterozygosity (28.0% vs 4.7%; P =.021), respectively.

A major limitation of the study was the small sample size, which did not allow for the effects of anti-IL-1 treatment to be examined among subgroups based on age or sex.

“Our study shows that anti-IL-1 agents represent an effective and safe treatment and may improve growth in children with colchicine-resistant FMF. Therefore, we suggest considering early treatment when needed, especially for those who harbor the M694V homozygous mutation,” the study authors concluded.


Pinchevski-Kadir S, Gerstein M, Pleniceanu O, et al. Effect of interleukin‑1 antagonist on growth of children with colchicine resistant or intolerant FMF. Pediatr Rheumatol Online J. 2023;21(1):4. doi:10.1186/s12969-022-00784-6