Effect of intra-articular adipose-derived mesenchymal stromal cell versus placebo injection on pain and function in patients with knee osteoarthritis: the ADIPOA2 phase 2b randomised clinical trial

This study aims to evaluate the efficacy of intra-articular autologous adipose-derived ex vivo expanded mesenchymal stromal cells (ADSC) on patient-reported outcome (pain and function) in symptomatic mild-to-moderate tibiofemoral knee osteoarthritis (OA). Participants were randomised in a prospective, double-blind, controlled phase 2b study to receive 1 single intra-articular injection in 3 separate groups: ADSC low dose 2 × 106 cells; ADSC high dose 10 × 106 cells; or saline placebo. The primary outcome was the rate of OsteoArthritis Research Society International (OARSI)/Outcome MEasures in Rheumatology (OMERACT) 'strict responders' defined by improvements from baseline reported to 0 to 100 mm scale in Western Ontario and McMaster University Osteoarthritis index (WOMAC) pain or physical function subscores ≥50% with minimal absolute changes ≥20 mm at 6 months. Secondary outcomes included an evaluation of WOMAC pain, WOMAC function, quality of life (36-Item Short Form Health Survey), WOMAC and Knee injury and OA Outcome Score global change, magnetic resonance imaging cartilage thickness changes and safety from baseline to 12-month follow-up. One hundred thirty-five patients were randomised from September 2016 to March 2022 (mean age, 58.3 [SD, 6.5] years; 58 [43%] women), 99 (73%) received allocated intervention, and 97 were analysed. After 6 months, treatment with ADSC versus placebo injection, 26 patients (47.3%) versus 23 patients (54.8%) were strict OARSI/OMERACT responders (relative risk 0.86 [95% CI: 0.58-1.28]; P = .46). Individuals showed different patterns in cartilage thickness change between timepoints across tibiofemoral articular surfaces, but overall secondary outcomes showed no significant-group differences. Among patients with symptomatic mild-to-moderate knee OA, a single intra-articular injection of 2 × 106 or 10 × 106 autologous ADSC compared with injection of saline placebo did not significantly improve pain and function. ClinicalTrials.gov Identifier: NCT02838069, https://clinicaltrials.gov/study/NCT02838069/EudraCT number: 2015-002125-19, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-002125-19.