Sustained pain improvement and IL-12-related biomarker changes in rheumatoid arthritis patients initiating baricitinib or TNF inhibitor therapy

Objectives The Janus kinase (JAK) inhibitor baricitinib has demonstrated analgesic effects that may extend beyond anti-inflammatory mechanisms. This study investigated longitudinal pain trajectories and their association with interleukin (IL)-6 and IL-12 changes in patients with rheumatoid arthritis (RA) initiating baricitinib or tumour necrosis factor inhibitor (TNFi) therapy. Methods In this single-centre prospective study, 60 patients with RA initiating baricitinib (n = 29) or TNFi therapy (n = 31) were followed at baseline, 2 weeks and 3 months. Healthy donors (n = 15) served as a biomarker reference. IL-6, IL-12p40, and IL-12p70 were measured using Enzyme-Linked Immunosorbent Assay (ELISA) and multiplex technology. Pain was assessed using numerical rating scales, and disease activity and function using 28-joint Disease Activity Score–erythrocyte sedimentation rate and Health Assessment Questionnaire Disability Index. Analyses were within-group and exploratory; adjusted mixed-effects models assessed between-group trajectories. Results Within both groups, disease activity, function, and all 3 pain domains improved significantly over 3 months. Under baricitinib, average pain and swollen joint count (SJC) improved further between 2 weeks and 3 months, whereas TNFi showed earlier improvement at 2 weeks. IL-6, IL-12p40, and IL-12p70 showed within-group reductions under baricitinib, reaching significance at 3 months. Adjusted models showed no robust between-group differences. Conclusions In this small prospective pilot cohort, both therapies were associated with early, clinically relevant pain improvement, with continued improvement in average pain and SJC under baricitinib. This sustained response was accompanied by within-group reductions in IL-6 and, notably, the IL-12 subunits, a JAK/tyrosine kinase(TYK)-linked pathway that has been less explored in relation to RA pain. These exploratory observations are hypothesis-generating and warrant confirmation in larger, adequately powered studies.