Misoprostol may be effective for obscure GI bleeding originating from the small bowel in patients taking aspirin or NSAIDs, a small recent study indicates.
Researchers in the United Kingdom performed a randomized, double-blind, placebo-controlled phase 3 trial to compare treatment with misoprostol and placebo in adults who had small-bowel ulcers and had been taking low-dose aspirin (defined as 75 to 325 mg/d), NSAIDs, or both for at least four weeks. Patients were eligible if they had evidence of obscure GI bleeding (defined as iron deficiency anemia, a decrease in hemoglobin concentration of ≥20 × 103 mg/L, or positive results on a fecal occult blood test) and normal results on upper endoscopy and colonoscopy.
An interactive voice response system randomly assigned patients to receive 200 micrograms of oral misoprostol or placebo four times per day for eight weeks. The study's primary end point was complete healing of small-bowel ulcers and erosions as assessed by video-capsule endoscopy. Analysis was by intention to treat. The study results were published May 9 by The Lancet.
One hundred four patients were initially included in the study, 52 of whom were assigned to receive misoprostol and 52 of whom were assigned to receive placebo, but two of the patients assigned to the former group were later found to be ineligible. Almost all patients were white, and 53% were men. Seventy percent of patients in the misoprostol group and 65% of those in the placebo group were taking low-dose aspirin for cardiovascular protection, and 44% and 38%, respectively, were taking nonselective NSAIDs for osteoarthritis.
At week eight, 27 of 50 patients in the misoprostol group and 9 of 52 patients in the placebo group experienced complete healing (54% vs. 17%; percentage difference, 36.7% [95% CI, 19.5% vs. 53.9%]; P=0.0002). Twenty-three patients in the misoprostol group and 22 patients in the placebo group had adverse events (46% vs. 42%), most commonly abdominal pain (20% vs. 25%), nausea or vomiting (18% vs. 13%), and diarrhea (22% vs. 12%). Severe adverse events were noted in four patients in the misoprostol group and zero patients in the placebo group (8% vs. 0%). Treatment adherence rates were similar between groups, with 76% of those assigned to misoprostol and 90% of those assigned to placebo taking more than 75% of the study drug.
The researchers noted that it is difficult to distinguish small-bowel ulcers from erosions on capsule endoscopy and that their study was done at only one center in mostly white patients, among other limitations. However, they concluded that consistent with previous research, misoprostol appears to be more effective than placebo for treating small-bowel ulcers and erosions in patients who are taking low-dose aspirin or NSAIDs and experience obscure GI bleeding. Misoprostol could allow patients to continue therapy with aspirin and NSAIDs, but its potential benefit must be weighed against its potential side effects, the authors wrote. They stressed that the drug should not be used in women of childbearing age unless they are also using reliable methods of contraception.
An accompanying comment noted that most of the patients in the study did not have significant anemia and that misoprostol treatment did not appear to cause an increase in hemoglobin concentration after eight weeks, indicating that the clinical relevance of obscure GI bleeding in this study may have been questionable. However, the comment author also acknowledged that it is important to understand how to treat small-bowel erosions, ulcers, and enteropathy, since they do cause problems for some patients, and said that such patients “might reasonably be treated with misoprostol on the basis of this study.”
The comment author pointed out that adherence in the study was poor and that the benefits of misoprostol treatment probably only last as long as the drug is continued. “Optimum treatment duration and issues regarding compliance, cost, and long-term safety of misoprostol require further investigation,” he wrote. “More studies are needed to answer these questions.”