Beneficial effects of NSAIDs peak early in knee osteoarthritis
medwireNews: A meta-analysis of 72 randomized controlled trials including 26,424 participants with knee osteoarthritis suggests that the beneficial pain-relief effects of oral NSAIDs peak at 2 weeks, while minor adverse events (AEs) begin to appear at 4 weeks.
“Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen,” Raveendhara Bannuru (Tufts Medical Center, Boston, Massachusetts, USA) and colleagues write in Arthritis Care & Research.
At 2 weeks, patients treated with NSAIDs experienced significantly greater improvements in average pain scores, most commonly measured on the WOMAC scale, than those given placebo, with a standardized mean difference (SMD) from baseline of 0.43, a difference the researchers describe as “statistically significant [and] clinically important,” using a cutoff of 0.37 to define clinical significance.
However, the SMD decreased to 0.36 at 8 weeks and to 0.21 at 26 weeks, figures that retained statistical significance but lost clinical significance. Findings were similar for functional improvements, with NSAIDs showing statistically significant but declining benefits over placebo from 2 weeks (SMD=0.45) to 26 weeks (SMD=0.19).
Meanwhile, individuals taking NSAIDs were more likely than those on placebo to experience a minor gastrointestinal AE, with the difference in risk showing as early as 4 weeks after starting treatment (risk ratio [RR]=1.38) and continuing at 12 (RR=1.36) and 26 weeks (RR=1.55). And although the overall risk for a minor cardiovascular event was higher in patients taking NSAIDs compared with placebo, this did not reach statistical significance in the combined analysis of all NSAID classes.
When NSAIDs were separated by class, traditional NSAIDs “performed consistently better” than celecoxib and intermediate cyclooxygenase inhibitors in terms of pain, and “outperformed” the other classes in functional improvement, say the researchers. However, traditional NSAIDs had the least favorable safety profile, with patients taking these medications having the highest risk for both gastrointestinal and cardiovascular AEs at most time points.
These findings support current clinical practice guidelines on the use of traditional NSAIDs with a proton-pump inhibitor, or celecoxib with or without a proton-pump inhibitor, to minimize the risk for gastrointestinal AEs in patients with a moderate or high comorbidity risk, write the study authors. They add that their results also support guidelines indicating that “NSAIDs should be used at the lowest effective dose and for the shortest duration.”
The researchers conclude: “This information should be taken into account together with patient-specific safety profiles and preferences, comorbid conditions, and concomitant medications to aid clinicians in their decisions on the prescription of oral NSAIDs.”
By Catherine Booth
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