Familial Mediterranean Fever (FMF) and psoriatic arthritis: a higher risk than expected

Article title: Increased risk of psoriatic arthritis in patients with familial Mediterranean fever: a population-based cohort study.

First author: Amir Haddad

Journal: Rheumatology (Oxford)

Link to the article: https://doi.org/10.1093/rheumatology/keaf607

Author of the abstract: Dr Rim Bourguiba

Summary

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is associated with mutations in the MEFV gene and characterized by excessive activation of the interleukin-1 (IL-1)β pathway. Psoriatic arthritis (PsA) is a chronic inflammatory disease belonging to the spectrum of spondyloarthritis, whose pathophysiology notably involves the IL-23/IL-17 pathways and Th17 lymphocytes. Data concerning the association between FMF and PsA have remained limited until now.

This retrospective population-based cohort study was conducted using the database of the main Israeli health insurance organization (Clalit Health Services), covering approximately 4.9 million individuals, between 2010 and 2023. The authors identified 9,736 adults with FMF treated with colchicine, with no history of PsA, matched by age and sex to 97,360 non-FMF controls. Participants were followed until the occurrence of PsA, death, or the end of the study period.

The incidence of PsA was significantly higher in FMF patients than in controls (3.26 vs 0.9 per 1,000 person-years). After adjustment for demographic factors and comorbidities, FMF was associated with a more than three-fold increased risk of developing PsA (HR 3.52; 95% CI 2.48–5.0). Other factors independently associated with PsA in FMF patients were age, smoking, and high socioeconomic status. The presence of psoriasis was, as expected, the major predictive factor.

The clinical characteristics and therapeutic strategies of PsA were overall similar in patients with or without FMF, with the exception of more frequent use of targeted synthetic DMARDs in FMF-PsA patients.

These results suggest an increased susceptibility to PsA in FMF patients, possibly related to common immunopathological mechanisms involving IL-1β and Th17 activation. They highlight the need for increased clinical vigilance regarding inflammatory joint manifestations in FMF patients.

In practice, this work encourages active screening for symptoms suggestive of psoriatic arthritis (persistent joint pain, enthesitis, dactylitis) in patients with FMF, particularly in cases of psoriasis or associated risk factors.

VEXAS syndrome through a rheumatologist's lens: insights from a Spanish national cohort

Summarized by: le Pr Sophie Georgin-Lavialle

Reference: Garcia-Escudero P, VEXAS syndrome through a rheumatologist’s lens: insights from a Spanish national cohort, Rheumatology, 2025, 00, 1-9

PubMed link: https://pubmed.ncbi.nlm.nih.gov/39937690/

Summary:

VEXAS syndrome is a rare, acquired autoinflammatory disease first described in 2020, associated with somatic mutations in the UBA1 gene. This article presents a Spanish multicenter case series of 39 Caucasian male patients followed in rheumatology, with a mean age at diagnosis of 73 years and an average age at symptom onset of 67. Prior diagnoses included seronegative polyarthritis (n=9), relapsing polychondritis (n=6), Sweet syndrome (n=4), polymyalgia rheumatica (n=4), systemic lupus erythematosus (n=3), and medium-vessel vasculitis (n=3). The most frequent clinical features, in decreasing order, were skin lesions (87%)—mainly neutrophilic dermatosis—polyarthritis (82%), fever (79%), chondritis (51.3%), ophthalmologic involvement (48.7%) mainly periorbital edema, pulmonary involvement (38%), deep vein thrombosis (30.8%), and renal involvement (20%).

From a hematological perspective, 92% of patients had macrocytic anemia, and 46% had myelodysplastic syndrome. A monoclonal gammopathy was present in 25.6% of cases. Cytoplasmic vacuoles were found in 82% of patients.

The three main UBA1 mutations identified were M41T (36%), M41V (15.7%), and M41L (47%). A genotype-phenotype correlation was observed: M41V was associated with renal involvement, and M41T with deep vein thrombosis and thrombocytopenia. A novel mutation (c.209T>A; p.L70H) in exon 4 was also reported.

Most patients presented with macrocytic anemia (92%), sometimes associated with myelodysplasia (46%) or monoclonal gammopathy (26%). Bone marrow examination showed vacuoles in 72% of cases.

All patients received corticosteroids, with significant improvement after diagnosis, likely due to increased doses. IL-6 inhibitors (75%) and JAK inhibitors (77%)—especially ruxolitinib (90%)—showed good efficacy. TNF inhibitors were ineffective.

Eight patients (20.5%) died during follow-up, with 5 deaths directly attributed to VEXAS syndrome.

This study highlights the crucial role of rheumatologists in identifying VEXAS syndrome, particularly in men over 50 with atypical inflammatory presentations, macrocytic anemia, and corticosteroid dependence. The described genotype-phenotype correlations may be validated in larger cohorts and could help refine diagnostic strategies and guide treatment choices.

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX

First author: Hadjadj et al.

Link to article: DOI: 10.1136/ard-2024-225640

Summary:

Study Objective:

To assess the efficacy and safety of targeted therapies in VEXAS syndrome, an adult-onset autoinflammatory disease associated with somatic mutations in the UBA1 gene.

Methodology:

A multicenter retrospective study including 110 patients who received at least one targeted therapy. Complete response (CR) and partial response (PR) were defined based on specific clinical and biological criteria.

Results:

A total of 110 patients received 194 targeted therapies: 78 (40%) JAK inhibitors (JAKi), 51 (26%) IL-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) TNFα blockers, and 12 (6%) other targeted therapies.

At 3 months, the overall response rate (CR and PR) was 24% with JAKi, 32% with IL-6 inhibitors, 9% with IL-1 inhibitors, and 0% with TNFα blockers or other targeted therapies.

At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors.

Treatment-free survival was significantly longer with JAKi compared to other targeted therapies.

Among patients who discontinued treatment, reasons included primary failure, secondary failure, serious adverse events, or death, with varying rates depending on the therapy.

Conclusions:

JAK and IL-6 inhibitors show clinical benefits, while other therapies demonstrate lower efficacy. These findings require confirmation in prospective trials.