Effects of biologic and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on patient-reported outcome domains in rheumatoid arthritis: a systematic review and network meta-analyses

Introduction: Evidence from head-to-head comparisons of biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) is lacking. This systematic review and network meta-analysis (NMA) aims to evaluate the relative effects of b/tsDMARDs on the International Consortium for Health Outcomes Measurement (ICHOM) RA-relevant domains of pain, fatigue, activity limitation, and physical and mental health. Methods: A systematic literature search was conducted using the machine learning tool ASReview. Randomised controlled trials were included that compared DMARDs with placebo or other DMARDs and reported the effects on PROs from the ICHOM standard set for inflammatory arthritis. Random effects NMA were performed on PROs. Results: In total, 99 studies were included, with heterogeneity within comparisons ranging from low to very high (I²=0%–96%). Janus kinase inhibitors (mean difference (MD) Health Assessment Questionnaire: −0.13; 95% CI−0.23 to −0.04) and IL-6 inhibitors (MD: −0.13; 95% CI −0.27 to −0.00) were significantly better at reducing activity limitation than tumour necrosis factor inhibitors. Other significant differences between b/tsDMARD classes were not observed. The surface under the cumulative ranking curve demonstrated that rituximab was overall ranked best among b/tsDMARDs. IL-6 inhibitors ranked highest in the mental health domain (82%). Early RA (<3 years diagnosis) and worse baseline PRO scores were associated with larger improvements of PROs (p<0.05). Conclusions: Despite heterogeneity, the results of this study may help rheumatologists guide selection of b/tsDMARDs, taking into account PROs that are important to the patient or reflect their primary symptoms. Future research should investigate within-class differences between specific b/tsDMARDs and emphasise individualised, PRO-based augmentation within treat-to-target strategies.