Springer 2026 Press Review – Annals of Rheumatic Diseases

December 2025 to March 2026

Author: Elvis Hysa

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update

This 2025 update of the EULAR RA management recommendations was developed by 50 international experts. Methotrexate (MTX) with short-term glucocorticoids remains the first-line strategy; leflunomide or sulfasalazine are alternatives if MTX is contraindicated. Upon insufficient response after 3-6 months, a biological disease modifying anti-rheumatic drug (bDMARD) should be added directly, without switching to another conventional synthetic DMARD. JAK inhibitors may be considered after careful cardiovascular/malignancy risk assessment. In sustained remission, dose reduction is preferred over stopping DMARDs.

Risk of first and second keratinocyte cancers with JAKi, TNFi, and non-TNFi bDMARDs in RA

Huss et al. investigated the risk of keratinocyte cancer (KC) across biological and targeted synthetic disease modifyinganti-rheumatic drugs (b/tsDMARD) classes. KC incidence is rising and may be influenced by immunomodulatory therapies. Using the Swedish RheumatologyQuality Register (n=21,121), this study compared KC risk across drug classes. Compared with tumour necrosis factor alpha inhibitors (TNFi), the HR for first KC was 1.72 for JAKi and 0.81 for non-TNFi bDMARDs. Among patients with prior KC, the HR for a second KC was 2.76 for JAKi vs TNFi. The risk was primarily driven by basal cell carcinoma, supporting dermatological surveillance in JAKi-treated patients.

Results of a 1-year randomised double-blind placebo-controlled trial with methotrexate 25 mg/week in recently diagnosed polymyalgia rheumatica

Bolhuis et al. conducted a 52-week double-blind, placebo-controlled randomized controlled trial evaluating higher-dose methotrexate (MTX) in polymyalgia rheumatica (PMR). MTX is recommended as a glucocorticoid (GC)-sparing agent, but previous RCTs used low doses (7.5-10 mg/weekly) with conflicting results. Sixty-four recently diagnosed PMR patients wererandomised to MTX 25 mg/wk or placebo, alongside a 24-week GC-tapering protocol. GC-free remission (polymyalgia rheumatica activity score <10, no GCs) atweek 52 was achieved in 80% of the MTX group vs 46% placebo (risk difference34%, 95% CI ≥14%, p=0.004), supporting early introduction of higher-dose MTX in PMR.

Transcriptomic stratification predicts response to rituximab, abatacept, or the association of hydroxychloroquine and leflunomide in 3 randomised controlled clinical trials of Sjögren’s disease

Chevet et al. demonstrated that transcriptomic endotyping may guide treatment selection in Sjögren’s disease (SjD). Using whole-blood RNA sequencing, 210 SjD patients from 3 RCTs (hydroxychloroquine-leflunomide [HCQ-LEF], rituximab [RTX], abatacept) were classified into 4 endotypes. Cluster 1 (strong type I interferon [IFN] signature) showed higherSjögren’s Tool for Assessing Response (STAR) rates vs placebo (61.5% vs 32.6%, p=0.016), confirmed for RTX (61.1% vs 15.8%, p=0.012). Cluster 3 (B-cell/IFN signature) responded to HCQ-LEF (77.8% vs 0%, p=0.046). Cluster 2 (healthy-like) showed no response to any therapy, supporting their exclusion from future trials.

EULAR recommendations for the management of Behçet’s syndrome: 2025 update

Hatemi et al. updated the EULAR recommendations for Behçet’s syndrome through a 29-member multidisciplinary task force, producing 5 overarching principles and 12 organ-based recommendations. Colchicine remains first-line for mucocutaneous and joint involvement; apremilast or tumor necrosis factor alpha inhibitors (TNFαi) are recommended for refractory cases. The major change is the shift toward early use of monoclonal anti-TNFα antibodies (especially infliximab) as first-line for eye, vascular, and nervous system involvement, replacing the previous step-up approach with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). A randomized controlled trial showed infliximab superior to cyclophosphamide for vascular/central nervous system disease.

Identification of novel fibroblast subsets in diffuse cutaneous systemic sclerosis

Rosendahl et al. identified novel profibrotic fibroblast subpopulations in systemic sclerosis (SSc). Fibroblast activation drives excessive extracellular matrix (ECM) deposition in SSc, but the specific subpopulations involved remain unclear. Using single-cell RNA sequencing on 37,343 cultured dermal fibroblasts from 4 early diffuse cutaneous SSc patients and 4 controls, SSc-specific clusters with strong upregulation of CD9 and four and a halfLIM domain 1 (FHL1) were found (p≤0.0001). FHL1 protein was >4-fold higher in dcSSc vs controls. small interfering RNA knockdown of FHL1 downregulated the profibrotic cofactor vestigial-like family member 3 (VGLL3) and multiple collagens, while CD9 knockdown reduced FHL1 expression and ECM genes, suggestingCD9/FHL1 as potential biomarkers and therapeutic targets.

Treatment nonresponders in lupus nephritis exhibit persistent type I interferon signalling in monocytes

Kim et al. performed longitudinal single-cell RNA sequencing of peripheral blood mononuclear cells from 10 biopsy-proven lupus nephritis (LN) patients during induction with high-dose glucocorticoids and mycophenolate mofetil (MMF). Monocytes showed the most differentially expressed genes. Complete responders progressively suppressed type I interferon (IFN-I) signalling (β=-0.753, p<0.001), whereas nonresponders maintained persistent IFN-I activation (β=0.769, p<0.001). Bulk RNA-seq validation (n=13) confirmed 6 interferon-stimulated genes were downregulated by 3 months only in responders. Thissignature correlated with proteinuria (R²=0.435, p<0.0001) and disease activity (SLEDAI-2K; R²=0.352, p=0.0005).

Inhibition of the type I interferon receptor pathway protects against muscle weakness induced by dermatomyositis serum

Kaewin et al. showed that type I interferon (IFN) receptor signalling causally mediates muscle weakness in dermatomyositis (DM). Isolated murine muscles incubated with DM serum (n=9) developed significant force reduction, whereas healthy serum did not. Blocking the type I IFN receptor α/β subunit 1 (IFNAR1) or using the Janus kinase (JAK) inhibitor ruxolitinib abolished DM serum-induced weakness (p<0.01). Combined IFN-α and IFN-β — but neither alone — reproduced the effect. Transcriptomics confirmed downregulation of 10 IFN-inducible genes (including Ifit1, Mx2, Xaf1) upon IFNAR1 blockade, supporting pharmacological targeting of the IFNAR1/JAK-STAT pathway in DM.

Blinatumomab induces rapid B-cell depletion but short-lived clinical benefit in refractory systemic sclerosis

Scherlinger et al. evaluated the CD19-directed bispecific T-cell engager blinatumomab in 5 patients with severe, treatment-refractory anti-topoisomerase I-positive systemic sclerosis (SSc). A 14-day continuous intravenous infusion (9→28 µg/day) achieved rapid peripheral CD19⁺ B-cell depletion in all patients, with acceptable safety (grade 1-2 cytokine release syndrome [CRS] in 3, no neurotoxicity or severe infections). At 3 months, modified Rodnanskin score (mRSS) decreased by a median of 4 points and lung function transiently improved. However, B-cell repopulation occurred within 1 month and all patients relapsed by months 3-6, suggesting single-cycle treatment is insufficient for durable disease modification.

Intra-articular injection of autologous tolerogenic dendritic cells modifies the synovial immune landscape in rheumatoid and inflammatory arthritis

Nicorescu et al. evaluated the synovial immune landscape following intra-articular injection of autologous tolerogenic dendritic cells(tolDC) in patients with autoimmune arthritis. Analysing paired synovial biopsies from 7 participants (baseline and 14 days post-injection), they found no changes in global histopathology or adaptive immune cell subsets. However, tolDC treatment induced a significant, dose-dependent increase in myeloid cells expressing high levels of the inflammation-resolution marker MerTK. Furthermore, total MerTK+ myeloid cells inversely correlated with arthroscopic synovitis scores, suggesting tolDC therapy promotes a local pro-resolving immune environment.