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Long-term effectiveness of pain medications uncertain in knee OA
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The long-term effectiveness of pain medications for patients with knee osteoarthritis is uncertain, and larger randomized clinical trials are needed to answer questions related to pain control, according to data published in JAMA.
“This is the first meta-analysis in osteoarthritis (OA) that takes into account only long-term — defined as at least 12-month duration — clinical trials,” Lucio Rovati, MD, of Rottapharm Biotech and the University of Milan, told Healio Rheumatology. “In addition, this is a network meta-analysis — we could take into account virtually all available medications and all experimental pharmacological treatments with published studies.”
“Analysis of long-term data is particularly important because OA is a chronic and progressive disease, but most medications are studied mainly for their short-term effects — mostly up to 3-6 months only,” Rovarti later added. “This creates troubles when physicians have to perform a chronic management of their patients.”
To analyze the long-term outcomes, including symptoms and joint structure, of pain medications for knee OA, Rovarti and colleagues conducted a systematic review and network meta-analysis of randomized clinical trials with at least 12 months of treatment and follow-up. The researchers performed the search using MEDLINE, Scopus, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials, focusing on studies published through June 30, 2018.
The researchers identified 47 studies that met their eligibility criteria — placebo-controlled trials at least 1 year in duration that compared active pharmacological treatments for knee OA with another intervention. The primary outcome was mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure. Rovarti and colleagues calculated standardized mean differences (SMD) and mean differences with 95% credibility intervals.
According to the researchers, the 47 studies included analysis covered bone-acting agents, such as bisphosphonates and strontium ranelate; antioxidants; NSAIDs; intra-articular injection medications, including hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis, including glucosamine and chondroitin sulfate; and putative disease-modifying agents, such as cindunistat and sprifermin. Among the interventions, 31 were studied for pain, 13 for physical function and 16 for joint structure. Trial duration ranged from 1 to 4 years.
The NSAID 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) were both associated with decreases in pain. However, the researchers reported great uncertainty for all estimates compared with placebo. In their analysis — using the mean difference on a scale of 0 to 100, and excluding trials at high risk for bias — pain improvement remained significant only for glucosamine sulfate.
“Physicians should be aware that the clinical trial evidence to support long-term pharmacological management of knee OA is scarce,” Rovarti said. “None of the medications were significantly associated with long-term improvement in pain, except celecoxib and prescription-grade glucosamine sulfate. However, the effect size of celecoxib was not clinically relevant and not significant in high quality trials. In addition, safety concerns remain that discourage use of this and any other NSAID beyond short-term use. Prescription glucosamine sulfate — but not other glucosamine formulations — was significantly associated with improvement in pain, physical function and joint structure.” – by Jason Laday
Disclosure: Rovarti reports employment with Rottapharm Biotech. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Carrie Beach, BSN, RN-BC
As the worldwide leading cause of disability, osteoarthritis (OA) can be very difficult to treat in our patients as there have been very few new treatment options introduced over the past 15 years in comparison to rheumatoid arthritis. Most therapeutic agents used to manage OA have been predominantly studied only in short-term use.
In their study, Gregori and colleagues sought to review and analyze long-term (>12 months) trials focused on pharmacologic intervention of knee OA, to assist in establishing long-term outcomes of these treatment options.
The authors reviewed 31 pharmacologic interventions for pain, 13 for physical function, and 16 for joint structure, with interventions including oral medications such as acetaminophen, NSAIDs and doxycycline. Vitamins such as vitamin D and glucosamine were also studied, as well as injections of corticosteroids and hyaluronic acid.
Interestingly, celecoxib and glucosamine sulfate were both associated with improvement in pain; however, the association for celecoxib was small and not seen in further subgroup analysis. Glucosamine sulfate was also associated with improvement of physical function and joint structure.
Overall, though, there was uncertainty regarding the effect size of change in pain for all comparisons with placebo — larger trials are needed to resolve this uncertainty. Until these trials are conducted, we will continue to treat OA patients with the most reliable pharmacologic interventions available. I am optimistic that the future holds more hope for our OA patients in terms of effective treatment options.
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