Phenotype-Guided Rehabilitation Versus Standard Physiotherapy for Symptomatic Knee Osteoarthritis: A Pragmatic Randomized Controlled Trial

Abstract

Background: Knee osteoarthritis is a heterogeneous condition in which conventional rehabilitation yields variable outcomes, partly due to differences in dominant pain mechanisms, biomechanical impairments, and metabolic contributors; clinically applicable phenotype-based approaches may improve the effectiveness of conservative care. Objective: To compare the effectiveness of phenotype-guided rehabilitation versus standard physiotherapy on pain and functional outcomes in individuals with symptomatic knee osteoarthritis. Methods: In a pragmatic, assessorblinded randomized controlled trial conducted at a tertiary care rehabilitation center, 42 adults with symptomatic knee osteoarthritis were randomized to phenotype-guided rehabilitation or standard physiotherapy for 8–12 weeks. Participants in the intervention arm received rehabilitation matched to their dominant clinical phenotype (paindominant, strength/biomechanical deficit–dominant, or obesity/metabolic), while controls received standard knee osteoarthritis physiotherapy. The primary outcome was knee pain assessed using WOMAC or KOOS pain scores. Secondary outcomes included WOMAC function, numeric pain rating scale, 6-minute walk test, Timed Up and Go, adherence, and analgesic use. Results: Phenotype-guided rehabilitation resulted in significantly greater improvements in pain and function compared with standard care, with larger reductions in WOMAC pain (Δ −1.85, p=0.003), WOMAC function (Δ −6.02, p=0.001), and numeric pain intensity (Δ −1.55, p<0.001). Functional performance improved more substantially, with greater gains in 6-minute walk distance and Timed Up and Go, alongside higher adherence and reduced analgesic use. Conclusion: Phenotype-guided rehabilitation provides superior short-term clinical outcomes compared with standard physiotherapy and represents a pragmatic, implementable precision-rehabilitation strategy for knee osteoarthritis.