Background Colchicine 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.
Objectives To survey when and how physicians consider resistance to colchicine in FMF patients and to report how they handle this situation in their practise.
Methods We 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.
Results We 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%).
Conclusions Our 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 and additional behavioural approaches preventing disease flares could probably reduce the use of biologics.
Disclosure of Interest A. Corsia: None declared, S. Georgin-Lavialle: None declared, G. Grateau Consultant for: Novartis, SOBI, V. Hentgen Consultant for: Novartis, SOBI, A. Faye: None declared, P. Quartier Consultant for: Novartis, SOBI, Speakers bureau: Novartis, SOBI, I. Koné-Paut Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI