Background/Purpose: Familial Mediterranean Fever (FMF) is the most common autoinflammatory monogenic disease worldwide, and it is associated with mutations in MEFV gene. Colchicine is the gold standard treatment to prevent disease attacks and its most severe complication, inflammatory amyloidosis (AA). In clinical practice, patients under 50 kg are often reluctant to take high dose of colchicine (2,5mg/day). At present, there are no data on the relationship between colchicine dose and weight in patients with FMF. 

We aimed at describing the daily colchicine dose in a cohort of FMF patients with two pathogenic MEFV mutations. In addition, we described clinical characteristics of patients taking 2.5 mg/day of colchicine, to determine the weight and body mass index (BMI) of these patients.

Methods: From 2016 to June 2023, a retrospective evaluation of prospectively-followed up homozygous FMF patients at the French National Reference Centre was performed.  Only patients with 2 pathogenic or likely pathogenic variants in MEFV exon 10 and fulfilling Livneh’s criteria were included.

Results: Out of 272 patients, 149 were women (57.8%), with a mean age at inclusion of 42.95 (±16.39) years. The homozygous M694V (p.(Met694Val)) pathogenic variant was present in 82.35% of patients. At inclusion, patients had a mean weight of 67.78 (± 14.78) kg, and a BMI of 24.17 (± 4.63) kg/m². Colchicine was taken by almost all patients (95.95%). Thirty patients (11.03%) were treated with a daily colchicine dose of 2.5 mg. Comparing these patients with others, we found that patients treated with 2.5 mg/day were mostly women (p=0.018), with a lower mean weight (p=0.019). In this context, 26 patients (87% of that subgroup treated with 2.5 mg/day) weighed less than 50 kg. In addition, female sex correlated with higher values of daily colchicine dose (p= 0.0208). Instead, weight was not associated with colchicine dose (p= 0.4073).

Conclusion: No toxicity has been noted in patients treated with 2.5 mg of colchicine, including patients weighting < 50kg. Of note, most of these patients were women. This gender difference may be related to the fact that women require a higher dose of colchicine because of a more severe clinical picture. In this regard, a recent study has described an unconventional activation of pyrin, caused by endogenous steroid catabolites [1]. It is possible to suggest that disease flare occurring during menstrual cycle may be associated with the peak of progesterone catabolism. We may speculate that in our cohort the clinical picture of female patients requiring an increased daily dose of colchicine may be related to the hormonal background of these women, with a possible exaggeration of pyrin activation. However, treatment adherence is unknown, and there may be a disparity between the dosage advised and that taken by the patient. This is the first study to examine the question of colchicine dosage in relation to weight of FMF adult patients and to highlight a possible link with female gender. We advise clinicians to explain that colchicine treatment may be used daily up to 2.5 mg without toxicity if renal function is normal and no drug interactions are present.

[1] Magnotti F, et al. Cell Rep 2022. https://doi.org/10.1016/j.celrep.2022.111472.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-needed-daily-dose-of-colchicine-in-patients-with-familial-mediterranean-fever-may-be-higher-in-women-a-study-on-behalf-of-the-jir-cohort/