Intra-articular platelet-rich plasma demonstrates superior clinical and serum biomarker outcomes compared with corticosteroids and NSAIDs in late-stage knee osteoarthritis: a randomised controlled trial.

objectiveTo assess the efficacy of two autologous platelet-rich plasma injections (PRP) in treating late-stage knee osteoarthritis and their effects on joint pain, stiffness and function as well as serum biomarkers reflecting inflammation, and cartilage turnover.

methodsNinety patients (aged 40-80 years) with symptomatic KL 3-4 KOA on arthroplasty waiting lists were randomized to PRP (two injections one week apart) and CS (a single injection of betamethasone), or NSAID (aceclofenac tablets) as the control groups. Primary outcomes included VAS pain scores, WOMAC scores, opioid use, and serum biomarkers (COMP, MMP-3, CGRP, CCL2, VEGF, IL-6, IL-18, TNF-α, CX3CL1, sTREM2, sRAGE, TGF-β1, BDNF) were measured at baseline, 3 months, and 6 months.

resultsEighty-two patients completed the 6-month follow-up. Baseline characteristics (VAS, WOMAC) were comparable among the groups. PRP treatment resulted in significant and sustained reductions in VAS pain scores at 3 and 6 months compared with those at baseline (p < 0.001) and in both control groups (3 months: p < 0.001 vs. CS and NSAID; 6 months: p = 0.004 vs. CS; p = 0.002 vs. NSAID). WOMAC total and subscale scores (pain, stiffness, function) improved significantly only in the PRP group at both follow-up points (all p ≤ 0.03), with significant intergroup differences favoring PRP. Opioid consumption was significantly lower in the PRP group than in the CS and NSAID groups at 3 months (p = 0.002 and p = 0.025, respectively) and than in the CS group at 6 months (p = 0.006). At 3 months, PRP significantly reduced levels of proinflammatory and cartilage degradation biomarkers (COMP, MMP-3, IL-6, IL-18, TNF-α) and CGRP compared with controls, while increasing levels of anti-inflammatory markers (sTREM2, sRAGE, TGF-β1). Several effects were maintained at 6 months, including continued reductions in COMP, IL-6, and IL-18 levels compared with the CS group and in IL-6 and TNF-α levels compared with the NSAIDs group. No significant changes were observed in MCP-1, VEGF, CX3CL1, BDNF, or β-NGF. Adverse events were mild and transient in the PRP group.

conclusionTwo PRP injections demonstrated greater 6-month clinical and biomarker improvements compared to CS and NSAIDs in late-stage KOA, supporting PRP as a safe bridge therapy prior to arthroplasty.