NSAID efficacy in OA peaks at 2 weeks, wanes over time
Although NSAIDs provide significant pain and functional improvements in patients with osteoarthritis, such effects peak at 2 weeks and decrease over time, while the incidence of gastrointestinal and cardiovascular adverse events begins to rise, according to data published in Arthritis Care & Research.
“The duration of NSAID efficacy and timeline of adverse event onset have been understudied,” Raveendhara R. Bannuru MD, PhD, FAGE, of Tufts Medical Center, told Healio Rheumatology.
“Given the chronic nature of knee OA symptoms and the resulting need for long-term therapeutic solutions, it is important to assess the benefits and risks of any drug — including NSAIDs — in its temporal context,” Bannuru and colleagues wrote. “Understanding the durability of the efficacy of oral NSAIDs, as well as the time course of onset of minor adverse effects, is key to this decision-making process.”
To analyze the efficacy and adverse effects of oral NSAIDs in patients with OA, Bannuru and colleagues conducted a systematic review and meta-analysis of randomized, placebo-controlled trials published through May 2018. The researchers searched Medline, EMBASE, Web of Science, Google Scholar and the Cochrane Central Register for controlled trials, specifically focusing on studies that assessed NSAID efficacy and safety compared with placebo in human participants, with no restrictions on publication date, status or language.
The initial search produced 1,607 potentially relevant trials, of which 191 were eligible for a full-text review. The researchers ultimately identified 72 trials, representing 26,424 participants, that met the inclusion criteria and were included in the final analysis. NSAIDs assessed in the included studied were celecoxib in 35 trials; naproxen in 18 trials; diclofenac in 11 trials; nabumetone in seven trials; ibuprofen in six trials; meloxicam in three trials; etodolac in two trials; and indomethacin and piroxicam in one trial each.
According to the researchers, NSAIDs produced moderate, statistically significant improvements in pain, which peaked at 2 weeks (standardized mean difference = –0.43; 95% CI, –0.48 to –0.38). However, their efficacy decreased over time, with patients’ functional improvements demonstrating similar decreases.
In addition, gastrointestinal adverse-effect rates were, by week 4, significantly higher in patients treated with NSAIDs, compared with the placebo groups (RR = 1.38; 95% CI, 1.21-1.57). Incidence of cardiovascular affects in patients who received NSAIDs was not significantly different from those reported in the placebo group. Most gastrointestinal and cardiovascular events were minor.
“Clinicians and patients should remain mindful of the efficacy and safety trajectories of NSAIDs when formulating a pain management regimen,” Bannuru said. “NSAIDs can provide effective symptom relief over short-term periods of up to 12 weeks. Though adverse events begin to manifest early, the side effects are mild. However, we would advise caution in prescribing consistent NSAID regimens for a duration of 12 weeks and beyond.”
“Our data suggest that after this point, the efficacy and safety trade-off of NSAIDs may no longer be favorable,” he added. “This is particularly important for patients who have chronic conditions that necessitate consistent pain management along with managing other comorbidities.” – by Jason Laday
Disclosure: Bannuru reports consulting fees from Fidia Pharma. Please see the study for all other relevant financial disclosures.