Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee OsteoarthritisThe RESTORE Randomized Clinical Trial

Question  Does intra-articular injection of platelet-rich plasma (PRP), compared with placebo saline injection, improve symptoms and joint structure in patients with knee osteoarthritis?

Findings  In this randomized clinical trial that included 288 adults aged 50 years or older with mild to moderate radiographic knee osteoarthritis, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 on an 11-point scale (range, 0-10) and a mean change in medial tibial cartilage volume of −1.4% vs −1.2% at 12 months. Neither comparison was statistically significant.

Meaning  Among adults with mild to moderate knee osteoarthritis, treatment with PRP vs saline injection did not significantly improve knee pain or slow disease progression.

Importance  Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.

Objective  To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.

Design, Setting, and Participants  This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.

Interventions  Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants).

Main Outcomes and Measures  The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up.

Results  Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 points, respectively (difference, −0.4 [95% CI, −0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was −1.4% vs −1.2%, respectively (difference, −0.2% [95% CI, −1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.

Conclusions and Relevance  Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.

Trial Registration  Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347