Perioperative Biologic and Targeted DMARDs in Patients with Rheumatic Diseases Undergoing Orthopedic Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Biologic (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have revolutionized the management of inflammatory rheumatic diseases. However, their perioperative use in orthopedic surgery presents a clinical dilemma between increased infection risk and disease flare upon discontinuation. OBJECTIVES: To evaluate the impact of perioperative continuation versus withholding of bDMARDs/tsDMARDs on postoperative complications, inflammatory biomarkers, drug-related toxicities, and disease flare. METHODS: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched up to January 2025. Randomized controlled trials and observational studies were included. Risk of bias was assessed using RoB 2.0 and the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Certainty of evidence was evaluated using GRADE. RESULTS: Sixty-seven studies were analyzed (42 contributing quantitative data; 51,394 unique patients). The primary SSI outcome (k=16) encompasses the complete patient pool (N=51,394). Perioperative continuation of bDMARDs/tsDMARDs was associated with increased SSI risk (corrected OR 1.27; 95% CI 1.12-1.44) and a non-significant trend toward higher PJI risk after data correction (corrected OR 1.24; 95% CI 0.88-1.75). Continuation significantly reduced disease flare risk (OR 0.41; 95% CI 0.29-0.58). Continuation was also associated with lower perioperative CRP and IL-6 levels. CONCLUSIONS: Perioperative continuation of bDMARDs and tsDMARDs increases infection risk but reduces disease flare. Management should be individualized, considering drug-specific risks, including biomarker suppression and thromboembolism.