The first meta-analysis of long-term pharmacologic treatments for knee osteoarthritis (OA) found little evidence that most prescribed medications improve pain control or preserve joint structure after 12 months of treatment. There was a small but statistically and clinically significant benefit from prescription-grade glucosamine sulfate .

The study, by Dario Gregori, PhD, from the Unit of Biostatistics, Epidemiology, and Public Health, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Italy, and colleagues, was published online December 25 in JAMA. The analysis may have more implications for clinical trial design than for clinical practice. David S. Jevsevar, MD, vice chairman, Department of Orthopedics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told Medscape Medical News that these treatments will produce long-term relief.

"All of the conservative interventions for knee OA are generally intended to address the acute exacerbations of knee OA or the chronic ache component The effect of these treatments, and that may also help to explain the small effect sizes, I do not think there is anything new here, "Jevsevar explained. Senior author Lucio C. Rovati, MD, CEO, and Chief Scientific Officer of Rottapharm Biotech, which was funded by the study, told Medscape Medical News that there were 33 randomized controlled trials (RCTs) of knee OA drug therapy with follow-ups of at least 12 months but that they were disappointed that only 13 of the 33 interventions had been studied in two or more trials. 

Chronic and Progressive Disease

"The question is, why, in a chronic and progressive disease, medications are studied, and most guidelines are unclear." This is a major limitation, and regulators should convince sponsors to run long-term If you are looking for a long-term label, you will need to know what to do for the long-term management of the disease, based on the available evidence , "Rovati said, Rovati added," Physicians should be aware that the clinical trial evidence to support long-term pharmacological management of knee OA is scarce. "

The authors extracted data from the RCTs and performed a Bayesian random-effects network meta-analysis to assess the baseline in knee pain (the primary outcome, measured using the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] or a visual analogue scale). Secondary outcomes were changes in physical function (measured using the WOMAC physical function scale) and in joint structure (measured as radiological joint space narrowing).

The authors explain, "Network meta-analyzes synthesize direct and indirect evidence in a network of trials that compare multiple interventions." This method allows comparison of all available osteoarthritis knee medications against placebo and between pharmacological agents despite the paucity of head-to-head comparisons of therapies in RCTs. "The trials included more than 20,000 patients with knee OA (70% women); the mean age ranged from 55 to 70 years.

The interventions included analgesics; antioxidants; bone-acting agents, such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications, such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs for osteoarthritis, such as glucosamine and chondroitin sulfate; and putative disease-modifying agents, such as cindunistat and sprifermin. The RCTs tested 31 interventions for pain, 13 for physical function, and 16 for joint structure.