Intra‐articular injections of platelet‐rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis

Abstract Purpose To compare the long‐term clinical efficacy provided by intra‐articular injections of either Pure Platelet‐rich Plasma (P‐PRP) or sham saline to treat knee osteoarthritis (KOA). Methods This prospective, parallel‐group, double‐blind, multi‐center, sham‐controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow‐up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P‐PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow‐up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra‐articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P‐PRP. Results 610 participants (59% women) with KOA who received three sessions of P‐PRP ( n = 308, mean age 53.91 years) or sham saline ( n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3­fold (95% confidence interval 3.6–4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow‐up. However, only the P‐PRP group showed a sustained improvement in clinical outcome measurements at month 24 ( P < 0.001). There were statistically significant differences between the P‐PRP and sham saline groups in all clinical outcome measurements at each follow‐up time point ( P < 0.001). The benefit of P‐PRP was clinically better in terms of WOMAC‐pain, WOMAC‐physical function and WOMAC‐total at 6, 12, 24, and 60 months of follow‐up. No clinically significant differences between treatments were documented in terms of WOMAC‐stiffness at any follow‐up. A clinically significant difference favoring P‐PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow‐up. At 6 months after injection, TNF‐α and IL‐1β levels in synovial fluid were lower in the P‐PRP group ( P < 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm 3 in the P‐PRP group and 2311 mm 3 in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm 3 , 95% CI − 79 to 1320 mm 3 ; P < 0.001). Conclusions In this randomized clinical trial of patients with KOA, P‐PRP was superior to sham saline in treating KOA. P‐PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P‐PRP and saline being comparable in safety profiles.