Three injections of freeze‐dried platelet factor concentrate provide greater clinical response than single injection in the treatment of knee osteoarthritis

Abstract Purpose Single‐injection freeze‐dried platelet factor concentrate (PFC‐FD) has been shown to be safe and effective in the treatment of early knee osteoarthritis (OA) with clear advantages over other PRP processing methods. No previous clinical investigations have examined multiple PFC‐FD doses. The aim of this study was to assess the safety and effectiveness of one versus three PFC‐FD injections in patients with knee OA. Methods Patients with Kellgren–Lawrence (KL) Grade I–IV knee OA were prospectively recruited via shared decision‐making based on patient preference to receive either one ( n = 1054) or three ( n = 317) PFC‐FD injections. Patients completed a pre‐injection knee injury and OA outcomes survey (KOOS). Post‐injection, patients completed the KOOS at 1, 3, 6 and 12 months. Adverse events were documented. Response to treatment was assessed using the Outcome Measures in Rheumatology (OMERACT)‐Osteoarthritis Research Society International responder criteria. Multivariable modelling assessed treatment effectiveness, adjusting for patient differences. Results The three‐injection cohort demonstrated a small advantage in all KOOS subscales except quality of life (QOL) at 1 month (2.4–4.0 points, p < 0.0001–0.004), but this advantage disappeared by 3 months. When only early OA (KLI–II) was considered, the three‐injection cohort demonstrated higher improvement at 1, 3 and/or 6 months for most KOOS subscales. No such differences were observed for advanced OA patients. Multivariable analysis demonstrates that three‐injection patients were more likely to achieve responder status for KOOS‐Pain and KOOS‐activities of daily living (ADL) at 12 months (70.9% vs. 60.9%, p = 0.02 and 55.7% vs. 47.3%, p = 0.009, respectively). Overall patient‐level adverse events were higher in the three‐injection group (21.3% vs. 6.9%; p < 0.001), though adverse events per injection did not differ between groups (one‐injection 6.9%, three‐injection 8.6%; p = 0.19). Conclusion Based on non‐randomized allocation, a three‐injection PFC‐FD treatment protocol demonstrates a higher likelihood of clinical response compared to a one‐injection protocol, particularly for relief of early knee OA symptoms, without evidence of an adverse immune response. Level of Evidence Level II, prognostic prospective cohort study (patients enroled at different stages of disease progression).