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

Abstract

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.

Figure 1.. Flow of Participants Through the Trial

^aOn the Kellgren and Lawrence scale of radiographic osteoarthritis disease severity, grade 0 indicates no radiographic features of osteoarthritis; grade 1, doubtful joint space narrowing and possible osteophytic lipping; grade 2, definite osteophytes and possible joint space narrowing; grade 3, multiple osteophytes, definite joint space narrowing, sclerosis, and possible bony deformity; and grade 4, large osteophytes, marked joint space narrowing, severe sclerosis, and definite deformity of bone ends. ^bStratified for site (Melbourne or Sydney) and Kellgren and Lawrence grade (2 or 3). ^cIndicates the number of participants that completed at least 1 of the primary outcome measurements at 12 months. ^dTwo participants in the platelet-rich plasma group and 2 in the placebo group rejoined at 12 months after being unable to contact at the 2-month assessment.

Figure 2.. Overall Knee Pain Individual Participant 12-Month Changes and Group Summary of Changes

A, Each vertical line represents an individual participant, with participants ordered by baseline value (gray dots) and vertical lines extending up (worsened) or down (improved) to the 12-month values. B, Box plots show the summary of changes by group at each time point. Box tops and bottoms indicate the IQRs of the distribution; horizontal lines, medians; and whiskers, furthest points within 1.5× the IQRs. The data point outside of the whiskers is an outlier.