- First Online:
- Cite this article as:
- Barradell, L.B., Whittington, R. & Benfield, P. Pharmacoeconomics (1993) 3: 140. doi:10.2165/00019053-199303020-00007
- 5 Downloads
Misoprostol effectively prevents nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer and is the only agent currently indicated for this purpose. In addition, misoprostol is effective as prophylaxis against NSAID-induced duodenal ulcer. Because of the widespread use of NSAIDs, the cost of routine misoprostol prophylaxis would be high, and thus its pharmacoeconomic evaluation is an important factor in assessing the most appropriate role of misoprostol in this group of patients.
Current cost-benefit analyses undertaken in major European centres and the US have generally indicated that, depending on initial assumptions, misoprostol prophylaxis over a 3-month period is cost-saving in patients with osteoarthritis taking NSAIDs. The net savings (costs) realised were dependent on several variables, including the acquisition cost of misoprostol, silent ulcer rate and patients’ compliance. Importantly, misoprostol prophylaxis was consistently more cost-beneficial in elderly patients aged >60 to 65 years than in their younger counterparts. In contrast, in one study misoprostol was found to reduce patients’ quality of life and, although misoprostol therapy is potentially cost-saving to society, patients generally preferred no therapy.
A single study assessing the cost-effectiveness of misoprostol prophylaxis in preventing ulcerative complications concluded that primary treatment was not an economically viable option for all NSAID users. Misoprostol was most cost-effective in the prevention of recurrent or secondary gastric ulcer complications in ‘high-risk’ patients, for example patients aged over 60 years and patients with rheumatoid arthritis.
Thus, although there are areas of interest awaiting further pharmacoeconomic investigation, misoprostol prophylaxis appears to be cost-effective in elderly and high risk patients receiving NSAIDs. Additionally, misoprostol prophylaxis is cost-saving in elderly patients with osteoarthritis requiring NSAID therapy.
Approximately one-third of the adult population is affected by some form of arthritis, with more than 2 million US patients suffering from rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important long term therapeutic strategy for patients with arthritis, however, their use is coupled with adverse gastrointestinal effects. Spontaneous adverse reaction reports associated with NSAID use comprised 25% of all such reports in the UK over a 21-year period, with the substantial majority emanating from patients aged ≥60 years.
In patients receiving NSAIDs, the risk of hospitalisation is 5.2 times that of the general population, with patients >60 years being 3 times more likely to die than patients aged <60 years. In 1989 it was estimated that 2600 US patients with rheumatoid arthritis would die because of NSAID-induced gastrointestinal complications.
NSAIDs may damage the gastrointestinal mucosa by a variety of mechanisms, including the depletion of mucosal prostaglandins. Gastric ulceration due to chronic NSAID use is more common than NSAID-induced duodenal ulceration, and between 40 and 60% of ulcers are asymptomatic or ‘silent’. Neither the duration nor type of arthritic disease appear to influence the gastrointestinal disease process. Furthermore, whether there are any differences between individual NSAIDs in the pathogenesis of gastroduodenal damage has not been fully established.
Clinical Efficacy and Tolerability
Misoprostol is a synthetic analogue of prostaglandin E1 which has protective actions on the gastric mucosa. As prophylaxis against NSAID-induced gastroduodenal damage, misoprostol 400 to 800 μg/day in divided doses was more effective than placebo over a 3- to 12-month period. Misoprostol was more effective than histamine H2-receptor antagonists in preventing gastric ulcer, and reducing the occurrence of endoscopically-diagnosed duodenal and gastric lesions. Some investigators have found misoprostol 800μg daily to be better than placebo in preventing epigastric pain in patients with arthritis taking NSAIDs, but misoprostol was only slightly superior to placebo in relieving pre-existing abdominal pain.
Whether misoprostol prevents the complications of NSAID-induced ulceration awaits further study. However, compared with placebo, misoprostol significantly reduced recurrent bleeding in hospitalised patients with gastrointestinal haemorrhage. Misoprostol 800Mg daily is effective in the treatment of NSAID-induced gastroduodenal ulceration even when NSAID therapy is continued.
Diarrhoea is the most common adverse event associated with misoprostol therapy. The incidence of diarrhoea is dose-proportional and is generally mild and self-limiting, seldom necessitating withdrawal of misoprostol therapy. To minimise the risk of diarrhoea, it is recommended that misoprostol be taken with food. Misoprostol has abortifacient potential and as such is con-traindicated in pregnant women or those wishing to become pregnant. Adequate contraception must be used by women of child-bearing potential taking misoprostol.
Misoprostol prophylaxis has been subjected to cost-benefit, cost-effectiveness and cost-utility analyses. Most studies have assessed the economic considerations of misoprostol as prevention for gastric ulcer only. Cost-benefit studies have generally demonstrated that 3-month misoprostol prophylaxis against gastric ulcer is cost-saving in patients with osteoarthritis being treated with NSAID therapy, although these analyses have been sensitive to changes in misoprostol acquisition costs, silent ulcer rates and patients’ compliance. Importantly, misoprostol prophylaxis was consistently economically beneficial in elderly patients (aged >60 to 65 years) regardless of the initial assumptions made.
The cost-effectiveness of 1-year prophylaxis with misoprostol against the complications of NSAID-induced ulceration demonstrated that misoprostol is most cost-effective in elderly patients (>60 years). Misoprostol has maximum cost-effectiveness when used as secondary prophylaxis of NSAID-induced ulcer complications in ‘high risk’ patient groups, including elderly patients and patients with rheumatoid arthritis. In a Canadian study, misoprostol was cost-effective in elderly and ‘high-risk’ patient groups.
One cost-utility analysis in 60 patients found that misoprostol prophylaxis reduced the patients’ quality of life because of the occurrence of diarrhoea. The effect of withdrawal of NSAID therapy on quality of life in this group was not determined.
Thus, misoprostol therapy is considered to be most cost-saving when used in elderly patients (>60 to 65 years) needing continued NSAID therapy.