Familial Mediterranean Fever and infertility: a possible role of inflammation

Article title: Novel use of interleukin-1 antagonists in male familial Mediterranean

fever patients with infertility: Case series

First author: Bugra Egeli

Journal: Archives of rheumatology

Link to the article: https://pubmed.ncbi.nlm.nih.gov/39507831/

Author of the abstract: Dr. Catherine Grandpeix-Guyodo

Introduction:

The main treatment for familial Mediterranean fever (FMF) is colchicine. Interleukin-1 (IL-1) inhibitors are used in cases of colchicine resistance in FMF.

Fertility disorders with azoospermia or oligospermia have been described in FMF; colchicine is often held responsible but this could be related to chronic inflammation induced by FMF.

Patients and methods: This article reports the cases of 2 men followed for FMF and suffering from infertility who successfully conceived embryos in vitro after stopping colchicine and starting treatment with IL-1 inhibitors.

Results:

Case N°1: A 38-year-old man with FMF, with homozygous M69V mutation of MEFV, treated with 2 mg colchicine/day had failed to conceive for 15 years despite 5 IVF attempts and stopping colchicine after the first 2 IVF. Semen analysis was macroscopically normal, with normal sperm count but decreased motility. Treatment with anakinra (IL-1 RA) was started, resulting in satisfactory semen analysis after 4 months and the obtaining of 2 genetically normal embryos compatible with transfer.

• Case N°2: A 33-year-old man suffering from FMF, with a heterozygous M694V mutation of MEFV, treated with colchicine for 14 years, presented with infertility with azoospermia. The failure of a first IVF under colchicine motivated its discontinuation and the prescription of Canakinumab. Successive sperm analyses showed progressive improvement in sperm motility which allowed, during the 5th IVF, the conception of a child.

Discussion:

These two cases show reversibility of Infertility under IL-1 inhibitors in FMF in 2 men: The introduction of anti-IL1 instead of colchicine allowed improvement in sperm quality in both cases.

Colchicine resistance is suggested as a predictive factor for infertility in FMF patients, suggesting that better control of inflammation may improve it.

Conclusion:

Infertility in men with FMF could be reversible and anti-IL1 could become the treatment of choice in FMF men with fertility disorders.

2025: A Year Rich in Autoinflammation, FMF, and VEXAS

In 2025, together with the team of the CEREMAIA Reference Center (Tenon Hospital, AP-HP / Sorbonne University), within the FAI2R network and the European Reference Network ERN RITA, we carried out extensive work focused on:

Familial Mediterranean Fever (FMF) and pyrin-associated diseases,

VEXAS syndrome, a prototype of hemato-inflammatory diseases,

AA amyloidosis and other rarer autoinflammatory diseases.

🔬 FMF and pyrin

We contributed to the update of the international EULAR/PReS recommendations for FMF, which incorporate recent advances regarding colchicine resistance and the use of biologic therapies (published in Annals of the Rheumatic Diseases, 2025).

Several studies based on the adult cohort of our reference center explored the following aspects: iron deficiency, liver involvement, FMF onset after the age of 65, the optimal daily dose of colchicine, and patients’ and prescribers’ perceptions of colchicine treatment.

We also conducted biological and genetic research on variants of the MEFV gene and pyrin-associated diseases, as well as on the role of IL-18 as a monitoring biomarker and as a specific signature of diseases involving the pyrin inflammasome.

🧬 VEXAS syndrome

In collaboration with the French VEXAS group and the MINHEMON club:

international reviews and recommendations were developed to structure the diagnosis and management of VEXAS syndrome, including a consensual definition of “flares,” infectious risks, and therapeutic strategies;

studies focused on specific organ involvement (kidney, nervous system, erythroblastopenia), as well as a multicenter study on VEXAS in women and across different ethnic backgrounds.

🧩 AA amyloidosis and other rare autoinflammatory diseases

We participated in a systematic review on AA amyloidosis in inflammatory rheumatic diseases, highlighting the importance of long-term strict control of inflammation.

We authored literature reviews on autoinflammatory actinopathies, A20 haploinsufficiency, and undifferentiated autoinflammatory diseases.

We also published work on diagnostic delay and the clinical presentation of cryopyrin-associated periodic syndromes (CAPS) in adulthood.

🧠 Therapeutic patient education programs

We continued the deployment of our three therapeutic education programs dedicated to AA amyloidosis, cryopyrinopathies (CAPS), and FMF. These programs aim to help patients and their relatives better understand the disease, treatments, monitoring, and warning signs.

In 2025, we notably led a session dedicated to CAPS during the weekend organized in July by the Muckle-Wells / CINCA association, in close collaboration with patient associations.

🎥 Patient webinars and online information

We launched a series of informational webinars for patients and their relatives on FMF, as well as educational videos on rare autoinflammatory diseases (AA amyloidosis, VEXAS syndrome, etc.), freely available on the CEREMAIA Tenon YouTube channel: CEREMAIA Tenon – Patient Webinars. These formats allow us to translate research findings and recommendations into practical messages for patients’ daily lives.

• All of this work shares a common goal:

• to better characterize these rare diseases,

• to refine diagnostic and monitoring strategies,

and ultimately, to provide more personalized and safer care for patients.

We warmly thank the patients, healthcare teams, colleagues from rare disease networks, and international partners for their commitment.

For those who would like to access specific articles in more detail, please feel free to contact us via private message or by email at:

ceremaia-medecine-int.tenon@aphp.fr

Happy New Year 2026, A new year to advance autoinflammation, together

The entire CEREMAIA Tenon team sends you our best wishes for the new year.

The past year has been rich in exchanges, scientific progress, and collaborations around autoinflammatory diseases, Familial Mediterranean Fever (FMF), VEXAS syndrome, AA amyloidosis, and other rare diseases. Above all, it has been marked by a shared commitment: to better understand these complex diseases and improve patient care in a concrete way.

In 2026, we will continue this commitment by:

• Developing clinical, biological, and genetic research,

• Elaborating and sharing international recommendations,

• Strengthening patient education programs,

• Continuing accessible information initiatives for patients and their families.

• We warmly thank all patients, care teams, associations, and our national and international partners for their trust and collaboration throughout the year.

May this new year bring progress, hope, and shared projects for the benefit of rare diseases and autoinflammation.

Wishing you a wonderful year ahead.

The CEREMAIA Team – Tenon Hospital, AP-HP / Sorbonne University