Padova, Italy—Pharmacists fill a lot of prescriptions for long-term pain control in knee osteoarthritis, but a new study suggests the efficacy of those medications remains uncertain.

The JAMA article points out that, although osteoarthritis is a chronic and progressive disease, pharmaceuticals have primarily been evaluated over short-term periods, which has made effectiveness unclear for long-term disease management.

Italian researchers from the University of Padova and colleagues conducted a meta-analysis of published research in an effort to determine long-term—a year or more—effectiveness of treatment. The focus was on outcomes, including symptoms and joint structure.

To do that, they searched databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials until this past summer for randomized, controlled trials of patients with knee osteoarthritis who had treatment and follow-up lasting a year or longer.

Defined as the primary outcome was the mean change from baseline in knee pain, with secondary outcomes including physical function and joint structure, which was measured radiologically as joint-space narrowing.

Meeting the criteria were 47 RCTs, involving 22,037 patients, generally age 55 to 70 years and a majority women. The following medication categories were 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 in osteoarthritis such as glucosamine and chondroitin sulfate; and disease-modifying agents such as cindunistat and sprifermin.

In the trials lasting from 1 to 4 years, researchers analyzed 31 interventions that were studied for pain, 13 for physical function, and 16 for joint structure. Results indicate that associations with decreases in pain were found for the nonsteroidal anti-inflammatory drug celecoxib (SMD, -0.18 [95% CrI, -0.35 to -0.01]) and the symptomatic slow-acting drug in osteoarthritis glucosamine sulfate (SMD, -0.29 [95% CrI, -0.49 to -0.09]), although there was large uncertainty for all estimates versus placebo.

In fact, the association with pain improvement remained significant only for glucosamine sulfate when data were analyzed using the mean difference on a scale from 0 to 100 and when trials at high risk of bias were excluded.

The review also found associations with improvement in joint space narrowing for glucosamine sulfate (SMD, -0.42 [95% CrI, -0.65 to -0.19]), chondroitin sulfate (SMD, -0.20 [95% CrI, -0.31 to -0.07]), and strontium ranelate (SMD, -0.20 [95% CrI, -0.36 to -0.05]).

“In this systematic review and network meta-analysis of studies of patients with knee osteoarthritis and at least 12 months of follow-up, there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo,” study authors conclude. “Larger RCTs are needed to resolve the uncertainty around efficacy of medications for knee osteoarthritis.”

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