Misoprostol can help heal NSAID-related small-bowel ulcers and erosions

Last Updated: 2018-05-18

By Megan Brooks

NEW YORK (Reuters Health) - Misoprostol can effectively treat small-bowel ulcers and erosions in patients on low-dose aspirin or NSAIDs who have obscure gastrointestinal bleeding, suggest results of a phase 3 study.

Aspirin and NSAIDS use to be "infamous for causing bleeding from stomach ulcers," Dr. Ali Taha from University Hospital Crosshouse, in Kilmarnock, U.K., told Reuters Health by email. "However, this type of bleeding (upper gastrointestinal bleeding, which is visible) has been getting less and less common as it can be prevented by acid-inhibiting drugs. On the other hand, we have discovered that people using aspirin or NSAIDs have been losing blood further down in their digestive system (small bowel) even if they were given anti-acid drugs."

Small-bowel bleeding (now known as obscure GI bleeding) is now far more common than overt bleeding. It shows as iron deficiency anemia or microscopic/invisible blood in the stools, Dr. Taha explained.

In The Lancet Gastroenterology & Hepatology, online May 9, Dr. Taha and colleagues report results of a randomized, double-blind, placebo-controlled study of 102 patients with small-bowel ulcers who were taking low-dose aspirin, NSAIDs, or both for at least four weeks. The patients had evidence of obscure GI bleeding (iron deficiency anemia or positive fecal occult blood test) and normal upper endoscopy and colonoscopy.

After eight weeks of treatment, complete healing of small-bowel ulcers and erosions was observed in 27 (54%) of 50 patients on oral misoprostol (200 mcg four times daily) compared with nine (17%) of 54 patients on placebo (P=0.0002).

Adverse events occurred in 23 (46%) of 50 patients in the misoprostol arm and 22 (42%) of 52 patients in the placebo arm. The most common adverse events were abdominal pain, nausea or vomiting and diarrhea. No serious adverse events were reported.

"Misoprostol might represent a pharmacological treatment option for lesions causing obscure gastrointestinal bleeding that is associated with aspirin and NSAIDs, but its use should be balanced against the risk of side-effects," the researchers conclude in their article.

Dr. Taha told Reuters Health, "Patients with obscure bleeding need to be examined using a video capsule endoscope. If this shows ulcers then they would benefit from misoprostol which can heal these ulcers. Misoprostol should not be given to young women unless they are on very reliable contraceptive methods as it can cause abortion."

Writing in a linked comment, Dr. Timothy Rockall of Royal Surrey County Hospital NHS Trust, in Guildford, U.K., advises, "Patients with clinically important NSAID-induced or aspirin-induced small bowel erosions or ulcers might reasonably be treated with misoprostol on the basis of this study."

However, many questions remain, including optimal dosing, bearing in mind that 20% of patients in the misoprostol group withdrew from the study and only 76% took more than 75% of the prescribed drug, he notes.

"It is also reasonable to assume," writes Dr. Rockall, "that in patients with ulcers and erosions that heal in response to misoprostol, lesions will recur once treatment stops. So what treatment protocols are appropriate for patients who are on long-term NSAIDs by necessity with clinically significant small bowel erosions responsive to misoprostol? Optimum treatment duration and issues regarding compliance, cost, and long-term safety of misoprostol require further investigation. More studies are needed to answer these questions," he concludes.

The study did not have commercial funding. The researchers report no commercial ties relevant to the study.

SOURCE: https://bit.ly/2KmHU71 and https://bit.ly/2wFIdrG

Lancet Gastroenterol Hepatol 2018.