Early response to JAK inhibitors on central sensitization and pain catastrophizing in patients with active rheumatoid arthritis

Objectives: To evaluate the effect of 4 weeks of treatment with Janus kinase inhibitors (JAKis) on central sensitization (CS) and pain catastrophizing, and to determine the pain-related variables predictive of disease activity improvement, in patients with active rheumatoid arthritis (RA). Methods: Consecutive RA patients with active disease starting a JAKi have been enrolled in this prospective observational study. Patients have been assessed at baseline and after 4 weeks of treatment. The evaluation was comprehensive of disease activity [Simplified Disease Activity Index (SDAI) and ultrasonographic (US) score] and of questionnaires aimed at investigating primarily CS [Central Sensitization Inventory (CSI)] and pain catastrophizing [Pain Catastrophizing Scale (PCS)]. Differences (Δ values) between the final and baseline were studied with the t test, Δ values of the variables were correlated with each other using Pearson's test, and predictor variables for improvement in SDAI were also investigated using multivariate regression analysis. Results: A total of 115 patients were evaluated. Overall, all variables demonstrated significant improvement between baseline and final except the US score. In particular, CSI decreased from 36.73 to 32.57 (p < 0.0001), PCS decreased from 32.46 to 28.72 (p = 0.0001). ΔSDAI showed a significant correlation with both ΔPCS and ΔCSI (r = 0.466 and 0.386, respectively, p < 0.0001). ΔPCS was the only variable predictive of an improvement in SDAI (coefficient = 0.500, p = 0.0224). Conclusion: JAKis would appear to have a positive effect on pain-related variables, particularly CS and pain catastrophizing, for the genesis of which extra-synovial mechanisms are responsible.