Efficacy, tolerability, and safety of an oral enzyme combination vs diclofenac in osteoarthritis of the knee: results of an individual patient-level pooled reanalysis of data from six randomized controlled trials.

objectiveTo compare efficacy, safety, and tolerability of an oral enzyme combination (OEC) containing proteolytic enzymes and bioflavonoid vs diclofenac (DIC), a nonselective nonsteroidal anti-inflammatory drug in the treatment of osteoarthritis of the knee. MATERIALS AND

methodsThis was an individual patient-level pooled reanalysis of patient-reported data from prospective, randomized, double-blind, parallel-group studies in adult patients with moderate-to-severe osteoarthritis of the knee treated for at least 3 weeks with OEC or DIC. Appropriate trials were identified with a systemic literature and database search. Data were extracted from the original case-report forms and reanalyzed by a blinded evaluation committee. The primary end point was the improvement of the Lequesne algofunctional index (LAFI) score at study end vs baseline. Secondary end points addressed LAFI response rates, treatment-related pain-intensity changes, adverse events, and laboratory parameters.

resultsSix trials were identified that enrolled in total 774 patients, of whom 759 had post-baseline data for safety analysis, 697 (n=348/349 with OEC/DIC) for intent to treat, 524 for per protocol efficacy analysis, and 500 for laboratory evaluation. LAFI scores - the primary efficacy end point - decreased comparably with both treatments and improved with both treatments significantly vs baseline (OEC 12.6±2.4 to 9.1±3.9, DIC 12.7±2.4 to 9.1±4.2, effect size 0.9/0.88;

conclusionWhen compared with DIC, OEC showed comparable efficacy and a superior tolerability/safety profile associated with a significantly lower risk of treatment-emergent adverse events, related study discontinuations, and changes in laboratory parameters.