Nonsurgical Knee Osteoarthritis Treatments for Reducing Inflammation as Measured on MRI Scans: A Systematic Review of Randomized Controlled Trials

Background: Knee osteoarthritis (OA) is a debilitating condition, and synovitis is a structural marker of disease progression that can be identified on magnetic resonance imaging (MRI). Nonsurgical therapies have been developed with the goal of targeting this inflammation to reduce pain and slow disease progression.

Purpose: To review current randomized controlled trials (RCTs) that measured changes in pain outcomes and synovitis on MRI scans after nonsurgical treatment for persons with knee OA.

Study design: Systematic review; Level of evidence, 1.

Methods: The PubMed database was searched using the terms "knee osteoarthritis AND (synovitis OR inflammation)" for RCTs published between 2012 and 2022. Included were studies that collected both pain outcomes and quantitative measurements of synovitis on MRI scan before and after treatment; studies that investigated surgical treatments were excluded. We calculated standardized response means (SRMs) to analyze the effect sizes of treatment on pain and synovitis outcomes; SRMs were classified as having low responsiveness to treatment if <0.5, moderate responsiveness to treatment if between 0.5 and 0.8, and large responsiveness to treatment if >0.8.

Results: Included in the review were 9 RCTs. Vitamin D and exercise therapy were the only 2 treatments that improved both pain and synovitis outcomes in comparison with their respective control groups. Statistically significant group differences in favor of treatment were seen in changes in pain after lutikizumab (anti-interleukin-1α/β dual variable domain immunoglobulin; SRM, 0.22; P = .050), allogenic human chondrocytes transduced with retroviral vector encoding transforming growth factor-β1 (P = .0119 at 12 weeks, P = .120 at 52 weeks, and P = .0074 at 72 weeks), and Curcuma longa (turmeric; SRM, 0.35; P = .039 on the visual analog scale for pain and SRM, 0.47; P = .006 on the Western Ontario and McMaster Universities Osteoarthritis Index pain subscore). One study reported a statistically significant group difference in synovitis only after treatment with intra-articular methylprednisolone (P = .01 at 14 weeks and P = .0006 at 26 weeks).

Conclusion: Only vitamin D and exercise therapy were found to improve pain and synovitis after treatment in this review. Further research is needed to validate these findings and investigate alternative treatments for reducing pain and synovitis in persons with knee OA.