Knee Arthritis Pain Relief Peaks Early With Non-Steroidal Anti-inflammatory Drugs

This article is suggesting that NSAIDs like ibuprofen and naproxen don’t help knee arthritis after about 26 weeks.  They also point out that there is a 42% chance of experiencing an adverse event involving the gastrointestinal and/or cardiovascular system taking these drugs. ~ Dr. Broussard

Don’t expect relief to last beyond a few months

by Nancy Walsh, Senior Staff Writer, MedPage Today
March 29, 2019

Pain relief from nonsteroidal anti-inflammatory drugs (NSAIDs) in knee osteoarthritis (OA) was rapid but declined over time, a large meta-analysis demonstrated.

Data from 72 randomized controlled trials found that statistically significant reductions in pain peaked at week 2 of treatment, with a standardized mean difference from baseline of -0.43 (95% CI -0.48 to -0.38), according to Raveendhara R. Bannuru, MD, PhD, and colleagues from Tufts Medical Center in Boston.

However, the mean difference decreased to -0.36 (95% CI -0.43 to -0.30) by week 8 and to -0.21 (95% CI -0.39 to -0.03) by week 26 and subsequently was no longer statistically significant, the researchers reported online in Arthritis Care & Research.

The prevalence of OA is rising, and an estimated 14 million U.S. adults now live with symptomatic knee OA, with 65% being prescribed NSAIDs. The disease is chronic, with long-term therapy needed, even after joint replacement in some patients.

Moreover, “given the current need to limit utilization of opioid medications, NSAIDs can be expected to play an even larger role in clinical practice,” the researchers noted.

“Despite widespread use, a gap currently exists in our knowledge regarding the consistency and duration of the beneficial effects of NSAIDs on pain and functional outcomes in patients with knee OA, and the efficacy of these drugs has largely been tested in randomized controlled trials of short-term duration,” they wrote.

Detailed data on safety also are lacking, despite a general awareness that gastrointestinal and cardiovascular events can occur, especially in the older age group more likely to have OA.

Therefore, Bannuru’s group conducted a systematic review of the literature through 2018 for clinical trials of traditional NSAIDs (diclofenac, ibuprofen, indomethacin, naproxen, and piroxicam), selective COX-2 inhibitors (celecoxib), and intermediate COX inhibitors (etodolac, meloxicam, and nabumetone).

The 72 trials analyzed included more than 26,000 patients and had a median duration of 6 weeks. Median patient age was 62, and median body mass index was 31.5 kg/m2.

For functional improvement, benefits were significant by week 2, with a standardized mean difference of -0.45 (95% CI -0.52 to -0.38), and remained significant through week 26, when the mean difference was -0.19 (95% CI -0.32 to -0.07).

With regard to safety, the researchers found that NSAID users had an increased risk of treatment-related adverse events (RR 1.21, 95% CI 1.04-1.40), gastrointestinal events (RR 1.36, 95% CI 1.25-1.49), and CV events (RR 1.37, 95% CI 1.05-1.77). Most were transient and mild, with gastrointestinal events including diarrhea and dyspepsia and CV events most commonly being edema and hypertension. Comparison of the different types of NSAIDs found that the traditional agents showed the greatest efficacy, having effects on pain at week 2 that were 24% and 64% greater than the selective COX-2 inhibitor celecoxib or the intermediate COX inhibitors, respectively. The traditional NSAIDs also showed better functional improvements, with effects over time that ranged from 14% to 42% compared with celecoxib.

However, the traditional NSAIDs also had greater safety concerns, with patients being 42% more likely to report adverse events compared with those given placebo (RR 1.42, 95% CI 1.13-1.78). They also were 50% more likely to experience gastrointestinal events (RR 1.49, 95% CI 1.31-1.68) and 92% more likely to have cardiovascular adverse events (RR 1.92, 95% CI 1.17-3.16).

Patients receiving either celecoxib or an intermediate COX inhibitor were more likely to report gastrointestinal events than those given placebo, but had no greater risk for cardiovascular events.

The minor gastrointestinal and cardiovascular events occurred as early as week 2 and remained increased throughout follow-up, which was 26 weeks for gastrointestinal events and 12 weeks for CV events.

“Based on our findings coupled with the current literature, clinicians should weigh the likelihood of a decline in symptomatic benefit against the risk of early onset minor adverse events, along with the patient perceptions, tolerability, and preferences, when extending an NSAID treatment regimen beyond 12 weeks,” Bannuru’s group wrote.

Current guidelines recommend that traditional NSAIDs be used with proton pump inhibitors and that celecoxib be given either with or without a proton pump inhibitor, and that naproxen or celecoxib may lessen the risk of CV problems. “Clinical practice guidelines have also indicated that NSAIDs should be used at the lowest effective dose and for the shortest duration. The results of our study support these recommendations, demonstrating the rapidity with which minor negative reactions can occur during NSAID treatment,” the authors wrote.

They acknowledged that their analysis had a number of limitations, including minimal information on doses, possible attrition bias, and the likelihood that the general OA population is less healthy than patients included in randomized trials.