The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee

Intra-articular (IA) injections of plateletrich plasma (PRP) have been increasingly used in the nonoperative treatment of knee osteoarthritis (OA) but have considerable heterogeneity in both formulation and clinical results. Alpha-2-macroglobulin (A2M) is a large plasma protein found in PRP that inhibits cartilage-degrading enzymes and could be an efficacious OA treatment independently. The purpose of this study was to compare the short-term clinical efficacy of IA injection of A2M-rich PRP concentrate to conventionally prepared PRP and corticosteroids in the management of symptomatic knee OA.

This double-blinded, randomized, controlled clinical trial was conducted at a single medical center with enrollment from June 2018 to May 2019. Subjects with symptomatic Kellgren-Lawrence (KL) grade 2 or 3 knee OA were randomized to IA injection with A2M, PRP, or methylprednisolone (MP) and followed for 12 weeks post-injection. Knee pain and function were assessed at pre-treatment baseline and at 6-week and 12-week followup with patient-reported outcome (PRO) surveys including the visual analog scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, and Tegner score.

Seventy-five subjects were enrolled in the trial, of whom 68 (90.7%) completed the 12-week follow-up. The majority of subjects (73%) were female with a mean age of 59 years (range: 37 to 75 years). There were no significant differences in age (p = 0.30), sex (p = 0.44), or KL grade (p = 0.73) between treatment groups. By 12 weeks postinjection, the A2M group showed significant improvement in VAS, WOMAC, KOOS, and Tegner (p < 0.05), the PRP group showed no significant improvement in any PROs (p > 0.05), and the MP group showed significant improvement in Lysholm only (p = 0.01). However, the changes in PRO scores between baseline and 12-week follow-up did not significantly differ between the three groups (p > 0.05).

Alpha-2-macroglobulin IA injection shows comparable efficacy to PRP and corticosteroids in the treatment of mild-to-moderate knee OA. Alpha-2-macroglobulin treatment resulted in modest improvement in knee pain and function at 6-week follow-up, albeit inconsistently across PRO measures and to a similar degree as PRP and corticosteroids. Given its non-superior short-term efficacy compared to established IA injections, as well as its increased cost of preparation, A2M may not be a justifiable option for routine treatment of knee OA.