April 2026 to July 2026
Author: Omar Dhrif
Sex-specific autosomal susceptibility loci in systemic sclerosis: a genome-wide association study
Rodriguez-Martin et al. (doi: 10.1016/S2665-9913(25)00376-5) performed a sex-stratified genome-wide association study in 10,653 patients with systemic sclerosis (1,556 men, 9,097 women) and 18,043 controls. Eight sex-specific loci were identified, including one male-specific signal (BCL11A, odds ratio [OR] 1.32, 95% CI 1.20–1.45, p=8.4×10⁻⁹) and two novel female-specific signals (IRF4, OR 0.78, 95% CI 0.71–0.85; RPL3-PDGFB, OR 1.19, 95% CI 1.12–1.26). Functional analyses prioritised 39 candidate genes and flagged fostamatinib and dasatinib as repurposing candidates.
Efficacy and safety of enpatoran, a Toll-like receptor 7/8 inhibitor, in patients with skin manifestations of cutaneous or systemic lupus erythematosus: Cohort A of the phase 2 WILLOW trial
Morand et al. (doi: 10.1016/S2665-9913(25)00337-6) reported Cohort A of WILLOW, a double-blind dose-finding phase 2 trial of enpatoran, an oral Toll-like receptor 7/8 inhibitor, in 100 patients with cutaneous or systemic lupus erythematosus and a Cutaneous Lupus Disease Area and Severity Index-activity (CLASI-A) score ≥8. At week 16, adjusted mean change in CLASI-A was −64, −68 and −72 percentage points with enpatoran 25, 50 and 100 mg twice daily versus −44 with placebo (p=0.0002 for dose–response). Upper respiratory tract infection was the commonest adverse event.
Repurposing leflunomide and hydroxychloroquine to treat Sjögren’s disease (RepurpSS-II): a randomised, double-blind, placebo-controlled, phase 2b trial
Wong et al. (doi: 10.1016/S2665-9913(26)00075-5) randomised 46 patients with Sjögren’s disease and a EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) ≥5 to leflunomide 20 mg plus hydroxychloroquine 400 mg once daily (n=21) or placebo (n=25) for 24 weeks. The mean between-group difference in ESSDAI at 24 weeks was −4.14 (95% CI −6.56 to −1.71, p=0.0012). One serious adverse event, probably unrelated, occurred; gastrointestinal discomfort was most frequent (29% vs 16%). These results replicate RepurpSS-I.
Long-term durability of a time-limited methotrexate intervention in arthralgia at increased risk for rheumatoid arthritis (TREAT EARLIER): 5-year data from a randomised, placebo-controlled trial
van Mulligen et al. (doi: 10.1016/S2665-9913(26)00109-8) reported 5-year outcomes of TREAT EARLIER, in which 236 patients with clinically suspect arthralgia and subclinical joint inflammation received intramuscular methylprednisolone plus one year of methotrexate or placebo. Among 120 participants at increased predicted risk, benefit was restricted to anti-citrullinated protein antibody (ACPA)-negative patients: rheumatoid arthritis developed in 3/35 (9%) versus 10/31 (32%) (hazard ratio 0.24, 95% CI 0.07–0.87, p=0.018; number needed to treat 4), with sustained lower disability. No sustained effect was seen in ACPA-positive patients.
Effectiveness and persistence of biological and targeted synthetic treatment in patients with rheumatoid arthritis and chronic kidney disease: a multicentre, prospective cohort study
Fukui et al. (doi: 10.1016/S2665-9913(26)00046-9) analysed 12,123 initiations of biological or targeted synthetic disease-modifying antirheumatic drugs in the US CorEvitas registry, of which 1,266 (10.4%) occurred in patients with an estimated glomerular filtration rate below 60 mL/min per 1.73 m². Clinical Disease Activity Index remission was reached by 246/1,266 (19.4%) of those with reduced kidney function versus 3,025/10,857 (27.9%) with preserved function (adjusted hazard ratio 0.76, 95% CI 0.66–0.88). Treatments were generally well tolerated.
Omar Dhrif MD in Internal Medicine
Country: Tunisia / France
Omar is a Clinical Immunology and Internal Medicine
MD, from University Tunis El Manar currently working
in University Hospital Dijon Bourgogne, France.
His main clinical and research interests are focused
on Vasculitis, Global access to health care and
educational therapy. Omar is the past-Treasurer of the
Tunisian Association of Young Internists, Co-Founder
of the Francophonic Young Internists Group, member
of the Research Committee of the Tunisian Society of
Internal Medicine and American College of
Rheumatology Social Media Ambassador. Omar is a
member of the EMEUNET Social Media
sub-committee.