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To evaluate the efficacy of on-demand use of anakinra in patients with crFMF. The Gazi FMF cohort was established in the year 2010, and from that date, 689 patients with FMF diagnosed according to the Tel Hashomer criteria were registered. Attack type, duration, severity, and their impact on life were collected either by disease diaries or a mobile phone application (FMF AIDD, AppStore, and Playstore). A retrospective cohort analysis was made from records of patients who have ever been treated with IL-1 inhibitors. A total of 78 patients were treated with IL-1 inhibitors in our cohort. Among these, 15 patients were identified who received on-demand anakinra. Rationale for on-demand use was prominent prodrome or trigger for attacks and patient's personal claim. Six patients were switched from regular use and nine were directly started as on-demand use. All were using background colchicine in maximum tolerated doses. None of the patients had evidence of persistently elevated acute phase reactants or proteinuria. The median duration of on-demand anakinra use was 6 (3-36) months. Pre- and post- on-demand anakinra periods were compared. Patient reported attack severity (p = 0.002), duration (p = 0.001), frequency (p = 0.001), absenteeism (p = 0.002), and presenteeism (p = 0.002) were significantly improved. On-demand anakinra prevented progression of prodromes to full-blown attacks which was demonstrated by decrease in the rate of attack/prodrome ratio (p = 0.02). On-demand anakinra can be continued in ten subjects on long-term. On-demand anakinra significantly improved FMF attacks in certain patients which suggest this approach would be of benefit in daily practice in selected patients.

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.

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Objective Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items. Methods This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months’ follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items. Results One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency. Conclusion We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.