Essential elements for guiding patient segmentation in precision pharmacotherapy for rheumatoid arthritis: lessons up to 2025

INTRODUCTION: Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) have transformed rheumatoid arthritis (RA) management; however, individualizing treatment, balancing efficacy and safety remains challenging. AREAS COVERED: This narrative review summarized evidence guiding b/tsDMARD selection based on a literature search conducted in PubMed. First, we outlined efficacy-driven factors, including concomitant csDMARD use, serological markers, and C-reactive protein/interleukin-6-related pathways, that may support selecting particular mechanisms of action. Second, we discussed safety-oriented prescriptions in the context of heart failure, demyelinating disease, infection, malignancy. Third, we addressed organ-specific comorbidities, including interstitial lung disease, cardiovascular disease, osteoporosis and renal impairment. These comorbidities require proactive management and appropriate control of RA activity. We reviewed emerging evidence on difficult-to-treat RA, including registry findings suggesting beneficial therapies for patients with multi-drug refractory synovitis. EXPERT OPINION: Precision pharmacotherapy in RA requires cautious interpretation of complex 'precision medicine' studies, with close attention to study populations, reproducibility. We believe optimal care combines treat-to-target principles, structured safety screening, and shared decision-making. This approach uses comorbidity-based risk stratification to define safe options and then chooses among them based on expected efficacy. Long-term registry experience indicates that such a balanced strategy can reduce adverse events while maintaining high drug retention and remission rates.