A comprehensive review of phase 2/3 trials in osteoarthritis: an expert opinion.

Abstract

Osteoarthritis is a chronic, degenerative, and debilitating disease associated with significant long-term morbidity and disability. The pathogenesis of osteoarthritis is not completely understood but involves an interplay between environmental risk factors, joint mechanics, abnormal pain pathways and upregulation of inflammatory signaling pathways. Current therapeutic options for patients are limited to conservative management, minimal pharmacological options or surgical management, with significant caveats to all approaches. In this review we have set out to investigate current phase II/III clinical trials by undertaking a pubmed search. Examined clinical trials have explored a myriad of potential therapeutics from conventional disease-modifying anti-rheumatic drugs and biologics usually used in the treatment of inflammatory arthritides, to more novel approaches targeting inflammatory pathways implicated in osteoarthritis, cartilage degeneration or pain pathways. Unfortunately, most completed phase II/III clinical trials have shown little impact on patient pain scores, with the exception of the traditional DMARD methotrexate and Sprifermin. Methotrexate has been shown to be beneficial when used in the correct patient cohort (MRI proven synovitis). Sprifermin has the longest follow-up data of 5 years and has been shown to reduce loss of MRI-measured cartilage thickness and pain scores.