Background: Familial Mediterranean Fever (FMF) is the most common autoinflammatory monogenic disease worldwide, and it is associated with mutations in MEFV (MEditerranean FeVer) gene [1]. Colchicine is the gold standard treatment to prevent disease attacks and its most severe complication, inflammatory amyloidosis (AA) [2]. At present, there are no data on the relationship between colchicine dose and weight in patients with FMF.

Objectives: We aimed at describing the daily colchicine dose in a cohort of FMF patients. In addition, we described clinical characteristics of patients taking the maximum daily colchicine dose (2.5 mg), to determine the weight and body mass index (BMI) of these patients. In fact, patients under 50 kg are often reluctant to take such a daily dose of colchicine in clinical practice.

Methods: From 2016 to June 2023, a retrospective evaluation of prospectively followed homozygous FMF patients at the French National Reference Centre was performed. All patients consented to anonymous collection of their medical data via the JIR cohort.

Results: Out of 272 patients, 149 were women (57.8%) and 123 men (45.2%), with a median age at inclusion of 39 years [min 18- max 84]. The median age at onset of symptoms was 5.8 [0.2-33] years and at diagnosis 13.56 [1-56] years. The homozygous M694V (p.(Met694Val)) pathogenic variant was present in 82.35% of patients. Colchicine was taken by almost all patients and 18.38% were receiving biological DMARDs, mainly interleukin-1 inhibitors: anakinra (50%), canakinumab (35.7%) or anti-TNF (11.9%). AA amyloidosis complicated FMF in 4.2% of cases. At inclusion, patients had a mean weight of 67.78 (± 14.78) kg [min 37 – max 109], and a BMI of 24.17 (± 4.63) [min 15.2 – max 44.9]. Median serum creatinine was 64 mmol/L [34-721]. Median CRP was 6.4 mg/L [0.25-250], and median SAA was 7 [3-388]. Thirty patients (11.03%) were treated with a daily colchicine dose of 2.5 mg. Of these, 23 (76.67%) were women with a mean age of 36.57 (± 12.84) years. The mean weight was 61.74 (± 12.27) [min 37 – max 109], with a BMI of 22.83 (± 4.12) [min 15.2 – max 44.9]. In this context, 26 patients (87% of that subgroup) weighed less than 50 kg. In multivariate analysis, female gender was associated with higher values of daily colchicine dose (β=0.18, [0.03; 0.33], p= 0.0208). Amyloidosis (β=-0.74, [-1.09; -0.38], p <0.0001) and age (β=-0.01, [-0.01; -0.0], p= 0.0009) were associated with lower values of daily colchicine dose. Weight (β=0.0, [-0.01; 0.0], p= 0.4073) was not associated with colchicine dose.

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 since women require a higher dose of colchicine because of a more demanding clinical and laboratory picture. In this regard, a recent study has described an unconventional activation of pyrin, caused by endogenous steroid catabolites [3]. It is possible to suggest that disease flare occurring during menstrual cycle may be associated with the peak of progesterone catabolism. Overall, 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. It should be pointed out that 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. The importance of discussion with patients, is pointed out. 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.

REFERENCES: [1] Savey L, et al. Nephrol Ther. 2021. doi:10.1016/j.nephro.2020.02.013.

[2] Ozen S, et al. Ann Rheum Dis 2016. https://doi.org/10.1136/annrheumdis-2015-208690.

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

Acknowledgements: NIL.

Disclosure of Interests: None declared.