Autologous Cell Injections for Knee Osteoarthritis Display Greater Responsiveness Than Allogenic Cellular Products and Corticosteroids in a Sex-Dependent Manner.

Abstract

BACKGROUND Age-related knee osteoarthritis (KOA) is a debilitating and progressive whole-joint disease. Despite the increased use of cell-based therapies in clinical practice to alleviate KOA symptoms, there lacks robust evidence to guide their clinical utility. We recently reported the results of our randomized controlled trial comparing corticosteroid injections (CSI) to cell-based therapies of bone marrow aspirate concentrate (BMAC), stromal vascular fraction (SVF), and allogenic umbilical cord tissue in 480 patients with Kellgren-Lawrence grade 2 to 4 KOA, finding improvements in all groups at 1 year with no statistically significant differences between groups. Here, we further examine these data from our clinical trial using a responder/nonresponder approach. HYPOTHESIS Patients receiving a single injection of a cell-based therapy are more likely to be classified as responders than those receiving a CSI based on pain outcomes at 12 months. STUDY DESIGN Randomized controlled trial; Level of evidence, 2. METHODS We performed an analysis of 381 patients who completed 12 months' follow-up. Responders were defined as patients with a ≥25% improvement in pain scores on the visual analog scale (VAS) or Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS Our hypothesis was conditionally confirmed, with BMAC having a higher response rate than a CSI. The overall responder rate across all treatment methods at 12 months was 58.5% for the VAS and 44.9% for the KOOS. The adjusted odds ratio (aOR) of responder status according to the VAS for BMAC relative to CSI was 2.02 (95% CI, 1.09-3.76). Subgroup analyses identified the heterogeneity of treatment by sex. Male patients had higher odds of a positive response to cellular injections according to the VAS (aOR, 5.18 [95% CI, 1.93-13.85] for BMAC; aOR, 3.34 [95% CI, 1.23-9.06] for SVF; aOR, 2.85 [95% CI, 1.09-7.39] for umbilical cord tissue) relative to CSI. A higher proportion of female than male patients responded to CSI. Of the evaluated therapies, BMAC had the highest percentage of responders. Male patients, particularly those aged <60 years, responded more favorably to BMAC and SVF over other therapies. CONCLUSION In addition to comparing the mean outcomes of treatment groups to one another, comparing the proportion of patients in treatment groups who reach a specific improvement threshold, that is, "responders," can provide additional insight into which cellular therapies are most beneficial. The current results indicate that we can improve outcomes and guide the robust design of future clinical trials by identifying patient populations that are most likely to respond favorably to cellular and noncellular injections. This is a first step in personalized (precision-based) medicine for KOA. REGISTRATION NCT03818737 (ClinicalTrials.gov).