Abstract
Background/Objectives: Sodium polynucleotide (PN) injection has recently been considered as a potential intra-articular therapy for knee osteoarthritis (OA); however, there is limited evidence regarding the long-term consistency of repeated PN cycles. To evaluate the clinical effectiveness of repeated intra-articular PN injections after the initial 6 months of therapy in patients with knee OA, using nationwide claims data. Methods: We conducted a retrospective cohort study using data from the Korea Health Insurance Review and Assessment Service collected between 2020 and 2023. Patients who received PN injections for knee OA were classified into two groups based on the treatment cycle: Group 1 (single cycle) and Group 2 (re-administration). Surgical outcomes and symptomatic indicators, including pain-related hospital visits, arthrocentesis, nonsteroidal anti-inflammatory drug prescriptions, and antidepressant prescriptions, were analyzed. Results: A total of 142,322 patients were included in this study. Readministration of PN was associated with significantly lower rates of total knee arthroplasty (2.31% vs. 4.92%, p < 0.0001) and delayed time to surgery (252.0 vs. 176.6 days, p < 0.0001). Similar trends were observed for hemiarthroplasty, with a lower incidence (0.28% vs. 0.55%, p < 0.0001) and longer time to surgery (240.7 vs. 162.2 days, p < 0.0001) in the readministration group. All groups showed a timewise reduction in pain-related hospital visits and instances of arthrocentesis. Safety outcomes were not assessed in this claim-based dataset. Conclusions: Repeated cycles of PN injections provide sustained clinical benefits and may effectively delay the need for surgical intervention in patients with knee OA, supporting their possible role as a long-term conservative treatment option. Radiographic severity and safety outcomes were unavailable in this claims dataset, limiting the adjustment for baseline OA severity and restricting causal interpretation.