BackgroundColchicine is the standard treatment for familial Mediterranean fever (FMF), preventing attacks and inflammatory complications. True resistance is rare and yet not clearly defined. We evaluated physicians’ definition of colchicine resistance and report how they manage it.Patients and methodsWe recruited patients with a clinical diagnosis of FMF, one exon-10 Mediterranean fever (MEFV) gene mutation and considered resistant to colchicine, via networks of expert physicians. Clinical, biological characteristics and information about colchicine treatment (dose adjustment, compliance) were collected. The severity of FMF was assessed by the Tel Hashomer criteria.ResultsWe included 51 patients, most females (55%), mean age 34 ± 23.1 years years (range 4.7–86.3). Overall, 58% (27/47) patients had homozygous M694 MEFV gene mutations. Seventeen of 42 patients (40%) declared full adherence to colchicine treatment, greater for children (48%) than adults (22%). Physicians considered colchicine resistance with > 6 attacks/year (n = 21/51, 42%), > 4 attacks in the last 6 months (n = 13/51, 26%), persistent inflammation (n = 23/51, 45%), renal amyloidosis in (n = 6/28, 22%) of adult patients and intolerance to an increase in colchicine dose (n = 10/51, 19%), and other reasons (n = 13/51, 23%), including chronic arthralgia (n = 6/51, 12%). Interleukin 1–targeting drugs represented the only alternative treatments in addition to daily colchicine.ConclusionResistance to colchicine is rare (<10% of patients) and mostly observed in severe MEFV genotypes. The main reasons for physicians assessing resistance were severe clinical symptoms, persistent subclinical inflammation, and secondary amyloidosis. Low adherence to colchicine treatment is a key component of resistance.

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BackgroundColchicine is the standard treatment of FMF, preventing attacks and inflammatory complications in more than 90% of cases. Some patients, especially those carrying 2 M694V mutations in MEFV gene, may require doses higher than recommended overcoming disease manifestations. True resistance to colchicine may be exceptional but is still not defined on a consensus basis.IL 1 targeting drugs are effective but are expensive alternative treatments requiring rigorous indications in FMF.ObjectivesTo survey when and how physicians consider resistance to colchicine in FMF patients and to report how they handle this situation in their practise.MethodsWe performed a retrospective chart review of patients identified through reference centers and networks of inflammatory diseases expert physicians. We asked them to report their patients with a clinical diagnosis of FMF and at least one pathogenic MEFV mutation, in whom they considered resistance to colchicine. Patients with concomitant SPA or Crohn's disease were excluded. We collected their clinical data, genotypes, and more detailed information on colchicine treatment dose adjustment and compliance. Finally we tried to analyse the reason(s) to consider their patients as resistant to treatment and we collected the alternative attitudes treatments used.ResultsWe identified 42 patients from 7 to 86 years old (mean age (±SD): 28,2 ± 22.1 years old) recruited from 10 centers. Thirty six of them could be fully analysed and consisted of 14 males and 22 females with a clinical diagnosis of FMF and, in whom 15 were children before 16 years. Sephardim Jews were the most represented. (n=23, 64%). All patients carried pathogenic mutations in the exon 10 of the MEFV gene except one girl and a woman with a complex allele including MEFV deletion. The mean (±SD) maximal dose of colchicine given in adult patients was 1.8± 0.65 mg, and it was 1.7 ± 0.6 mg (0.1 ± 0.01 mg/kg) in paediatric patients. The level of CRP in between attacks was evaluated in 40 patients and reached a mean of 35,8 mg/L. Fourty percent of patients declared to be fully observant to colchicine treatment. The main reasons to consider resistance to colchicine treatment were: >6 attacks/year (44%), >4 attacks in the last 6 months (20%), persistent inflammation (41%) and other reasons (44%). Twenty percent of patients were intolerant to an increase of colchicine dose. Concomitant treatments to overcome FMF symptoms were essentially NSAIDS, steroids, and analgesics. Sixty five percent of these patients are currently treated with IL-1 targeted drugs including anakinra (48%) and canakinumab (17%).ConclusionsOur study has confirmed that resistance to colchicine treatment is rare (0–10% of patients, per investigating center) and more likely observed in patients carrying severe MEFV genotypes. In most cases the mean reasons to consider resistance to treatment were severe clinical symptoms and persistent subclinical inflammation, however low compliance to high doses of colchicine seems to play a major role. Patient's education...