medwireNews: Findings from a systematic review and network meta-analysis published in JAMA indicate that it is not clear whether pharmacologic treatments offer long-term benefits for patients with knee osteoarthritis (OA).
“Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management,” say the study authors.
Lucio Rovati (University of Milano – Bicocca, Monza, Italy) and co-workers analyzed data from 47 randomized controlled trials with at least 1 year of follow-up, comprising 22,037 participants in total.
The studies, which were either placebo-controlled or involved an active comparator, investigated 33 pharmacologic interventions. These included analgesics, antioxidants, bone-acting agents, nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injection agents, symptomatic slow-acting drugs in OA, and putative disease-modifying drugs.
Rovati and team report that “[t]here was a large amount of uncertainty around all the estimates” for the impact of drug treatments versus placebo on pain outcomes, with no significant improvement in pain observed with 93.5% of the interventions studied.
The symptomatic slow-acting agent glucosamine sulfate and the NSAID celecoxib were both associated with a significant reduction in pain outcomes versus control treatments, with standardized mean differences (SMD) of 0.18 and 0.29, respectively. Glucosamine sulfate remained significantly associated with improvements in pain when data were analyzed on a normalized 1–100 scale and when studies at high risk of bias were excluded from the analysis, but celecoxib did not.
“NSAIDs are the most widely used medications for osteoarthritis,” and have been associated with a “moderate effect” on pain outcomes in studies with up to 12 weeks of follow-up, write the researchers.
However, they say that given the “small” benefit seen with celecoxib and the lack of long-term pain reduction associated with other NSAIDs, “it may be premature to recommend any NSAID beyond short-term or intermittent treatment.”
The investigators note that analyses of the association between pharmacologic treatments and other outcomes were also “limited by considerable uncertainty.” Glucosamine sulfate was the only agent associated with a significant improvement in physical function (SMD=0.32) compared with placebo, while glucosamine sulfate, chondroitin sulfate, and strontium ranelate were significantly associated with reduced joint space narrowing (SMD=0.42, 0.20, and 0.20, respectively).
Although glucosamine sulfate was “consistently associated” with improvements in outcomes for OA patients, the study authors point out that “[o]ther glucosamines were not associated with benefit,” in accordance with previous meta-analyses that included mainly short-term studies.
The team concludes that “[l]arger randomized clinical trials are needed to resolve the uncertainty around the long-term efficacy of medications for knee osteoarthritis.”
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