August 2025 to November 2025
Author: Nikolaos Vlachogiannis
IL-17A Blockade Modulates Inflammatory and Stromal Pathways
in Peripheral Spondyloarthritis
Ihsan Hammoura et al. (10.1186/s13075-025-03638-0) found that IL-17A inhibition (IL-17Ai) profoundly alters synovial gene expression in peripheral spondyloarthritis, suppressing both inflammatory and stromal pathways. Transcriptomic analysis revealed that IL-17Ai independently regulated inflammation and bone-remodeling programs. While IL-17Ai consistently attenuated inflammation-related pathways in both psoriatic joints and skin, its effect on bone remodeling pathways was specific to the synovium. In contrast, IL-12/23 blockade did not affect tissue remodelling, despite mitigation of synovial proinflammatory pathways. These findings support tissue-specific mechanisms underlying the clinical efficacy of IL-17Ai in peripheral SpA.
Paternal DMARD Exposure and Adverse Birth Outcomes in Autoimmune Rheumatic Diseases
In a large population-based cohort, Yu-Hsuan Joni Shao et al. (10.1186/s13075-025-03641-5) found that paternal preconception exposure to DMARDs in fathers with autoimmune rheumatic diseases was associated with drug-specific risks for adverse birth outcomes (small for gestational age infants, preterm labour, and congenital abnormalities). Methotrexate showed no increased risk. Ciclosporin was linked to higher rates of preterm birth and very small for gestational age infants (~1.5-fold). Azathioprine (~1.5-fold), non-TNF biologics (~1.7-fold), and tsDMARDs (~5.2-fold) were associated with increased risk of congenital abnormalities, particularly cardiovascular, oral cleft, and musculoskeletal defects, especially when used in combination therapies.
Real-World Persistence of Secukinumab versus TNF Inhibitors
in Spondyloarthritis
In this real-world prospective cohort of 644 spondyloarthritis (SpA) patients, (10.1186/s13075-025-03664-y), secukinumab (n=214) demonstrated higher 4-year treatment persistence than TNF inhibitors (TNFi, n=430; 38.7% vs 30.5%, respectively), particularly in peripheral SpA (40% vs 18.2%, respectively). TNFi were more frequently discontinued due to both inefficacy and safety reasons. Persistence differed by patient characteristics: secukinumab performed better in obese female psoriatic arthritis patients (76% vs 39% for TNFi), while TNFi showed higher persistence in non-obese male axial SpA patients (78% vs 48% for secukinumab). Six-month clinical response rates were comparable between treatments across all SpA subtypes.
Comorbidity Burden Differentially Affects Olokizumab and Adalimumab Efficacy in Rheumatoid Arthritis
In this post hoc analysis of the CREDO-2 trial (10.1186/s13075-025-03682-w), baseline comorbidity burden, assessed by the modified Charlson Comorbidity Index, did not affect the clinical efficacy of the IL-6 inhibitor olokizumab in patients with active rheumatoid arthritis. Patients with and without comorbidities achieved similar CDAI, SDAI, and ACR50 responses at 3 and 6 months. In contrast, comorbidities were associated with reduced clinical responses to the TNF inhibitor adalimumab at 6 months. Comorbidity burden did not influence placebo responses or safety outcomes.
Machine Learning–Defined Psoriatic Arthritis Phenotypes
Predict Long-Term Response to Risankizumab
Using unsupervised machine learning (10.1186/s13075-025-03670-0), five distinct clinical phenotypes were identified among psoriatic arthritis (PsA) patients (n=1119) treated with the interleukin-23 inhibitor risankizumab in the KEEPsAKE trials. These phenotypes differed by joint distribution, enthesitis, and dactylitis patterns. Over four years of follow-up, risankizumab demonstrated sustained efficacy across all phenotypes. Highest rates of minimal disease activity or low DAPSA were observed in the “moderate-to-high disease activity” group (characterized by lower tender and swollen joint count, dactylitis, and enthesitis), and the “dactylitis and feet dominant” group (characterized by dactylitis and active joints primarily in the feet). This data-driven stratification supports future personalized treatment approaches in PsA.
Nikolaos Vlachogiannis
Nikos is a postdoctoral researcher in Rheumatology and Internal Medicine resident at the Medical School of the National and Kapodistrian University of Athens, Greece. His main clinical and research interests include systemic sclerosis, and specifically the pathogenetic mechanisms connecting vasculopathy / innate immunity with fibrosis. Nikos is also the EMEUNET country liaison for Greece and a member of the Social Media subcommittee.