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Misoprostol was most cost-effective if risk for NSAID-related GI events was high

ACP J Club. 1998 Jul-Aug;129:25. doi:10.7326/ACPJC-1998-129-1-025

Source Citation

Maetzel A, Ferraz MB, Bombardier C. The cost-effectiveness of misoprostol in preventing serious gastrointestinal events associated with the use of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 1998 Jan;41:16-25.



For patients with rheumatoid arthritis, is misoprostol cost-effective in preventing serious gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs)?


Cost-effectiveness analysis using data from a randomized controlled trial with 6-month follow-up (Misoprostol Ulcer Complications Outcome Safety Assessment [MUCOSA] study).


A multicenter study in North America (661 U.S. and 3 Canadian investigators).


8843 patients > 52 years of age (mean age 68 y) with rheumatoid arthritis. Patients were classified as having low, medium, or high baseline risk for serious GI events. Patients with a history of peptic ulcer disease were categorized as having medium risk, and patients who were > 75 years of age who had a history of peptic ulcer disease were considered to be at high risk.


4404 patients were allocated to NSAIDs and misoprostol, 800 µg/d, and 4439 patients were allocated to NSAIDs and placebo for 6 months.

Main cost and outcome measures

Costs were in Canadian dollars and included drugs, dispensing fees, and costs for inpatient surgical and medical management of serious GI events, outpatient visits with or without endoscopy of the upper GI tract, and management of side effects. Clinical outcomes were hospitalization for GI complications and number of endoscopies, GI radiographic series, and operations for GI complications.

Main results

The rate of definite or suspected upper GI complications was lower in the misoprostol group than in the placebo group (0.57% vs 0.95% {P = 0.04}* and 1.8% vs 2.2% {P = 0.05}*, respectively). Costs per event averted varied; the lowest cost was for patients at high risk for GI events (Table).


The cost-effectiveness of misoprostol in the prevention of serious gastrointestinal events induced by nonsteroidal anti-inflammatory drugs was greatest in patients at highest risk for these events.

Sources of funding: Wellesley Hospital Research Institute and Searle Canada.

For correspondence: Dr. A. Maetzel, Healthcare Research Division, Arthritis & Immune Disorders Research Centre, OCI-Princess Margaret Hospital, 610 University Avenue, Room 734, Toronto, Ontario M5G 2M9, Canada. FAX 416-946-2291.

*P values calculated from data in article.

Table. Rates per 1000 patients and cost per upper gastrointestinal event averted for misoprostol vs placebo*

Risk group Misoprostol rate (95% CI) Placebo rate Cost of event averted in Cdn $ (CI)
Low 5.7 (2.7 to 10.5) 9.5 (5.4 to 16.3) 94 766 (60 286 to 137 146)
Medium 9.3 (2.0 to 36.7) 28.2 (12.0 to 57.9) 14 943 (10 912 to 32 157)
High 14.8 (0.2 to 102) 57.4 (16 to 178) 4101 (-222 to 18 146)†

*Monte Carlo simulation analysis was used to derive 95% CIs for costs.
†Not significant.


Patients at high risk for NSAID-induced complications include elderly persons (> 75 y) and those with a history of peptic ulcer disease (1). This illuminating cost-effectiveness analysis based on the MUCOSA trial data (2) is the first to calculate the effectiveness of misoprostol in preventing major complications and the first to apply adequate assumptions (although 20% of patients do develop ulcers while receiving NSAIDs, probably 85% of NSAID-induced ulcers are silent). The data suggest that the costs to avert a serious complication with misoprostol prophylaxis in the highest-risk group are modest.

It should be noted that without misoprostol prophylaxis, approximately 10 in 1000 patients would have had an ulcer complication over a 6-month period compared with about 6 in 1000 patients receiving misoprostol. Each averted event, although rare, is expensive (about Cdn $95 000), and these averted events account for the favorable cost-effectiveness results. It is notable that misoprostol reduces the rate of serious complications by 40% and not 90%, as most have erroneously assumed on the basis of a 90% reduction of endoscopic ulcers (3). Moreover, misoprostol prophylaxis comes at a price—up to 25% of patients develop diarrhea, which may adversely affect quality of life, and this needs to be considered when prescribing this treatment (4). Alternate effective strategies with similar cost-effectiveness (high-dose H2 antagonists, proton pump inhibitors, and Helicobacter pylori eradication in patients with co-infections) now need attention. Currently, none of these treatments have been shown to effectively reduce clinically serious events.

Nicholas J. Talley, MD, PhD
University of SydneyPenrith, New South Wales, Australia

Nicholas J. Talley, MD, PhD
University of Sydney
Penrith, New South Wales, Australia


1. Talley NJ. Chronic peptic ulceration and nonsteroidal anti-inflammatory drugs: more to be said about NSAIDs? Gastroenterology. 1992;102:1074-7.

2. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:241-9.

3. Stucki G, Johannesson M, Liang MH. Is misoprostol cost-effective in the prevention of nonsteroidal anti-inflammatory drug-induced gastropathy in patients with chronic arthritis? A review of conflicting economic evaluations.Arch Intern Med. 1994;154:2020-5.

4. Gabriel SE, Matteson EL. Pharmacoeconomics. 1995;8:479-90.