Efficacy and safety of intra-articular disease-modifying osteoarthritis drugs (DMOADs) for knee osteoarthritis: a Bayesian network meta-analysis of randomised controlled trials.

Abstract

Knee osteoarthritis (KOA) is the most common degenerative joint disease and a major global health burden. Disease-modifying osteoarthritis drugs (DMOADs) aim to slow, halt, or reverse structural progression while relieving symptoms. This review evaluated the efficacy and safety of intra-articular DMOADs in patients with Kellgren-Lawrence grade 2-3 KOA. MEDLINE, EMBASE, ClinicalTrials.gov, WHO ICTRP, and Cochrane CENTRAL databases were searched from inception to 28 January 2026 for randomised controlled trials (RCTs) comparing outcomes between DMOADs and placebo or between different DMOADs. Bayesian network meta-analysis was performed to compare outcomes between DMOADs. Six RCTs with 2267 patients were included, involving four different DMOADs (Sprifermin, Lorecivivint, SB-061, and LNA043). Sprifermin ranked highest for total femorotibial cartilage thickness (SUCRA = 0.949; MD = 0.026 mm; 95% CrI: -0.012 to 0.071). Lorecivivint ranked highest in pain improvement (SUCRA = 0.658; MD = 2.33; 95% CrI: -18.8 to 22.5) and function (SUCRA = 0.834; MD = 4.47; 95% CrI: -7.57 to 16.5). However, all credible intervals crossed zero. SB-061 had the lowest risk of adverse events (SUCRA = 0.749; RR = 0.94; 95% CrI: 0.656 to 1.38); however, the credible interval crossed one. Current low-level evidence indicates that no intra-articular DMOADs provide significant structural or symptomatic benefit. This highlights the need for efficacious agents and optimised trial designs with standardised imaging protocols, clinically relevant endpoints, adequate statistical power, and long-term follow-up to accurately assess disease-modifying effects. Future studies should also evaluate novel DMOADs with improved efficacy and safety.