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

Familial Mediterranean Fever: a single dose of anakinra to stop an acute attack

Article title: A single dose of anakinra for arresting Familial Mediterranean Fever attacks: a proof-of-concept study

First author: E. Giat

Journal: Clinical and Experimental Rheumatology

Link to the article: https://pubmed.ncbi.nlm.nih.gov/41133353/

Author of the abstract: Dr Catherine Grandpeix-Guyodo

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is characterized by recurrent febrile attacks of serositis (peritonitis, pleuritis, arthritis) and may, in the long term, be complicated by AA amyloidosis in cases of uncontrolled chronic inflammation. Colchicine is the standard long-term treatment; however, some patients experience incomplete response or intolerance, leading to the continuous use of IL-1 inhibitors (anakinra or canakinumab). Nevertheless, acute attacks may still occur despite treatment, and their management remains largely symptomatic, with limited efficacy of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs).

Patients and Methods

The objective of this prospective study was to evaluate the efficacy of a single dose of anakinra (100 mg subcutaneously) administered at the onset of an attack to interrupt its progression. The study included patients with typical FMF according to Tel Hashomer criteria, carrying one or two pathogenic MEFV mutations, treated with colchicine, and having experienced at least two serositis attacks in the previous year. Patients receiving continuous anti–IL-1 therapy were excluded, as were those with atypical attacks or chronic inflammatory states.

Patients were provided with a prefilled syringe of anakinra and received training in self-injection and early recognition of attack symptoms. The duration of treated attacks was compared with each patient’s usual attack duration.

Results

Thirty-five patients agreed to participate: five were excluded due to persistent inflammation; four experienced no attacks during the study period; two did not ultimately use anakinra during an attack; and one discontinued due to an adverse event. A total of 23 patients were analyzed, including 13 with two pathogenic MEFV mutations (considered to have “classical” FMF) and 10 with a single pathogenic MEFV mutation (considered “heterozygous” FMF).

The mean duration of treated attacks was 8.3 ± 6.8 hours, compared with 56.3 ± 16.8 hours under usual conditions. When anakinra was injected within the first 4 hours of attack onset, 85% of attacks were interrupted within 4 hours after injection. Later injections resulted in a less pronounced but still significant reduction compared with usual attack duration. Overall, 91% of treated attacks lasted less than 24 hours. Only one adverse event was reported (local injection-site reaction), highlighting the good tolerability of this strategy.

Six patients continued to use self-purchased anakinra to treat 43 additional attacks, with similar results, confirming the reproducibility and feasibility of this approach in real-life conditions.

Discussion

The authors emphasize that this strategy is not an alternative to continuous treatment in colchicine-resistant or -intolerant patients. Rather, it should be considered a “rescue” therapy, allowing rapid interruption of occasional acute attacks, reduction of pain, avoidance of emergency department visits, decreased absenteeism, and improved quality of life.

Conclusion

This prospective study demonstrates the efficacy and safety of a single, early injection of anakinra to significantly shorten FMF attacks (both classical and heterozygous forms) in adults. A randomized controlled trial is currently underway to confirm these findings and to better define the optimal role of this strategy within the therapeutic armamentarium.

EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update

First author : Ozen S

Review: Annals of the Rheumatic Diseases

Reference: Ann Rheum Dis. 2025 Apr 9:S0003-4967(25)00084-6

Link to pubmed: EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update - PubMed

2024 European Recommendations on Familial Mediterranean Fever (FMF) – Summary:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. Due to its clinical and genetic variability, specialized management is essential. In 2024, the EULAR and PReS societies updated their guidelines.

General Principles:

• FMF requires specialist expertise for both diagnosis and management.

• The primary goal is complete control of inflammation, including subclinical inflammation, to prevent complications such as AA amyloidosis.

• Lifelong treatment is necessary, with strict adherence, primarily based on daily colchicine therapy.

• Care should be patient-centered, aiming to preserve quality of life.

Key Recommendations:

• Colchicine should be initiated as soon as a clinical diagnosis is made.

• The dosage must be tailored to tolerance and adherence (single or divided daily doses).

• If symptoms persist or subclinical inflammation remains, the dose should be increased within recommended limits (maximum 2 mg/day in children, 3 mg/day in adults).

• If colchicine fails despite good adherence, interleukin-1 blockers (anakinra, canakinumab) are recommended.

• Chronic musculoskeletal manifestations may require additional treatments (DMARDs, biologics).

• Regular monitoring (clinical, biological, toxicity, adherence) is essential.

• Colchicine should be continued during pregnancy and breastfeeding.

• During acute attacks, colchicine should be maintained at the same dose, with symptomatic treatment added (e.g., NSAIDs).

• A minimum core set of assessment criteria is proposed: attack frequency, quality of life, biological markers (CRP, SAA).

Quality indicators, clinical priorities (especially adherence), and implementation strategies are provided to harmonize care across centers.

Recommandations approuvées par l’EULAR et la PReS FMF.pdf

Download PDF • 1.05MB