Purpose: Intra-articular (IA) injections of corticosteroids and hyaluronic acid (HA) products are used to treat patients with knee osteoarthritis pain that has not responded to more conservative treatment. Corticosteroids are a standard of care despite only suggestive clinical evidence of 12 or more weeks of pain relief.

Method: A double-blinded, randomized, active controlled, multicenter non-inferiority trial with 442 subjects provided a pragmatic comparison of HA to methylprednisolone. Both groups received one intrar-ticular injection, and underwent pain and function evaluations over 26 weeks. The primary endpoint for study success was WOMAC pain responder rate at 12 weeks. The outcome of two prior trials influenced the patient selection criteria and provided a saline cohort for propensity score analyses comparing HA and methylprednisolone to saline.

Results: The responder rate of HA was non-inferior to methylprednisolone at 12 weeks. Reductions in WOMAC pain, stiffness and physical function scores at all time points, and improvements in time to ‘get-up-and-go’ and walk 10 meters occurred in both treatment groups. The trends favored the HA responder rates at the later time points while the methylprednisolone rate decreased significantly by 26 weeks. Propensity score analyses confirmed that the responder rates of meth-ylprednisolone and HA were statistically significantly superior to a saline control at 12 weeks.

Conclusion: The responder rate from a single injection of HA was non-inferior to methylprednisolone at 12 weeks, and the trend favored HA at later time points. The responder rates of HA and methylprednisolone were statistically significantly greater than that of saline at 12 weeks.