High Rate of GI Events Noted. A large European study has found that at-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis have a high incidence of gastrointestinal issues.
The study was conducted by Angel Lanas, MD of the University of Zaragosa School of Medicine in Spain and colleagues.
During their 6 month follow-up of GI events tied to NSAIDS in some at-risk patients with osteoarthritis, rheumatoid arthritis (RA) or ankylosing spondylitis, they found that the incidence rate of any GI adverse event was 19 per 100 person-years.
The findings, which were published in the April Annals of the Rheumatic Diseases, showed that the rate of uncomplicated GI events was 18.5 per 100 person-years; this includes adverse events such as dyspepsia, nausea and vomiting. The rate was 0.7 per 100 person-years for complicated events such as as hemorrhage or perforated ulcers.
The study, called EVIDENCE, was conducted to obtain a more real-world sense of GI adverse events linked to NSAID use. Current information about this risk comes from clinical trials, which usually exclude at-risk patients.
Data from 4,144 patients from 363 centers in 12 countries were included in the study
Data from 4,144 patients from 363 centers in 12 countries were included in the study. To take part in the study, patients had to have at least one risk factor for GI events, including being a age 60 or higher, a history of peptic ulcer and concomitant medications such as low-dose aspirin, anticoagulants, corticosteroids, or selective serotonin reuptake inhibitors (SSRIs).
Two risk factors were present in one-quarter of patients. One in ten patients were classified as high risk with three or more risk factors.
The primary endpoint of the study was the incidence of symptomatic uncomplicated or complicated GI events of both upper and lower GI tract. GI events in patients receiving or not receiving proton pump inhibitors (PPI) and the incidence of cardiovascular and other events were secondary endpoints.
NSAIDs were used for osteoarthritis in 85 percent of cases, 11 percent for RA, 3 percent ankylosing spondylitis and 1 percent for a combination of conditions. The most frequently used types of NSAIDs were diclofenac in 29 percent, ibuprofen in 19 percent and naproxen in 10 percent.
“Notably, the incidence of GI events (18.5 per 100 person-years for uncomplicated GI events and 0.7 per 100 person-years for complicated GI events) was higher than in previous non-interventional studies,” the authors stated, according to MedPage Today.
The efficacy of [NSAIDs] is well documented; however, the clinical benefits of NSAIDs
“The efficacy of [NSAIDs] is well documented; however, the clinical benefits of NSAIDs may be offset by an increased risk of dyspepsia, other abdominal symptoms, cardiovascular events (e.g., myocardial infarction, stroke, heart failure) and serious gastrointestinal complications such as peptic ulcer,” GI events associated with NSAID use can occur unexpectedly, which can complicate issues further.
PPIs were used by 28 percent of patients, who exhibited an event rate of 24 per 100 person-years. This compares to 15 per 100 among nonusers.
However, the researchers found that when they used a propensity-score analysis, patients continuously on PPIs had an incidence rate of 17 per 100 compared to 26 for those continuously off PPIs. These findings did not reach statistical significance, however.
The authors expressed concern over the finding that GI events were more common among high-risk patients even with PPI co-therapy. “In fact, PPI users had a higher incidence of GI events than nonusers.
Given the proven efficacy and effectiveness of PPIs in trials, these findings point to strong confounding by indication, confounding that could not be fully neutralized by propensity score modeling,” the researchers said.