WASHINGTON, DC—Glucosamine sulfate is the only agent consistently effective on symptoms and joint structure changes in patients with knee osteoarthritis (OA), the first systematic review and meta-analysis to investigate the effects of available medications used for at least 1 year concluded at the 2016 ACR/ARHP Annual Meeting.
Glucosamine sulfate, chondroitin sulfate, and strontium ranelate are effective only on structural changes, and no evidence of efficacy was observed for NSAIDs, corticosteroids, acetaminophen, putative disease-modifiers, most bone acting agents, or slow-acting drugs, noted Lucio C. Rovati, MD, of the Clinical Research Department, Rottapharm Biotech, Monza, Italy, and the University of Milano Bicocca, Milano, Italy, and colleagues.
“While management of OA should be directed to long-term control of symptoms and joint structure changes, existing pharmacological agents are mostly studied for their effects on symptoms for short-term periods,” Dr. Rovati noted in explaining the rationale for the study.
The investigators searched the Cochrane Library, Embase, Scopus and Web of Science for studies of randomized controlled trials (RCTs) of pharmacological interventions in knee OA published until February 29, 2016. They also screened reference lists of retrieved articles for additional trials. Eligible RCTs were those with treatment and follow-up of at least 1 year.
“The primary outcome was knee OA pain change from baseline to the endpoint (≥ 12 months) on a validated scale. Secondary outcomes were changes in physical function and joint structure expressed as radiologic medial tibiofemoral joint space narrowing (JSN),” they noted.
A random-effects network meta-analysis within a Bayesian framework was performed, with imputation methods for mean changes and variability measures adopted to include studies with incomplete data. “Quality of evidence was rated based on the GRADE approach,” they said.
Of the 5992 articles identified, 38, in 18,883 patients, met long-term eligibility criteria. The duration of the studies ranged between 1 and 4 years.
“Virtually all available pharmacological intervention categories” were found. These included 26 interventions versus placebo for pain, 13 for physical function, and 17 for JSN.
The interventions included acetaminophen, calcitonin, celecoxib, chondroitin sulfate, cindunistat, diacerein, diclofenac, etoricoxib, glucosamine, glucosamine plus chondroitin sulfate, glucosamine sulfate, hyaluronic acid (HA), HA plus methylprednisolone, HA plus triamcinolone, indomethacin, licofelone, naproxen, nimesulide, risedronate, rofecoxib, sprifermin, strontium ranelate, tiaprofenic acid, triamcinolone, vitamin D, and zoledronic acid.
They found no evidence of efficacy for most of the interventions compared with placebo except for glucosamine sulfate, which had a significant long-term treatment effect on pain and physical function: the Glass’ Delta Effect Size (ES) was -0.29 (95% credibility interval -0.49, -0.10) and -0.32 (-0.52, -0.12), respectively, “and high quality of evidence rated by GRADE.”
The only interventions found to reduce radiologic JSN significantly were glucosamine sulfate, chondroitin sulfate, and strontium ranelate: ES 0.42 (0.20, 0.64), 0.20 (0.08, 0.31), and 0.20 (0.06, 0.35), respectively.