Abstract
Osteoarthritis (OA) of the knee remains one of the most prevalent and disabling musculoskeletal conditions worldwide, with few disease-modifying options beyond joint replacement. The pro-inflammatory cytokine interleukin-1 (IL-1) has long been implicated in the pathogenesis of OA, and approaches to block IL-1 activity have included recombinant proteins, small molecules, autologous blood-derived biologics, and most recently, viral vector-based gene therapies delivering interleukin-1 receptor antagonist (IL-1Ra). Gene therapy platforms such as PCRX-201 (Pacira) and GNSC-001 (Genascence) represent a technical advance, aiming for durable intra-articular IL-1Ra expression from a single injection. However, these approaches are expensive, logistically complex, and face challenges of immune barriers to repeat dosing, cost of goods (COGS), and uncertain long-term safety, efficacy and cost-effectiveness.By contrast, autologous conditioned serum (ACS), marketed for human use as Orthokine (also Regenokine) and for veterinary use under trade names such as IRAP, IRAP ProEAS™, and IRAP II, delivers IL-1Ra directly to the joint using the patient's own blood. Though evidence is modest, ACS provides a mechanistically overlapping anti-inflammatory approach with lower cost, repeatability, and safety advantages. ACS is already clinically applied in Europe and in veterinary medicine in Europe and the U.S. whereas IL-1Ra gene therapy remains in mid-stage clinical trials. Until gene therapy demonstrates clear advantages in durability, disease modification, and cost-effectiveness, ACS may represent a more pragmatic and earlier option in the sequence of intra-articular treatments, ahead of where gene therapy would enter, in selected clinical contexts for targeting IL-1 in patients with knee OA.