Making Sense of NSAID Gastropathy and Considering the Therapeutic Options

Abstract

There is increasing recognition that nonsteroidal anti-inflammatory drugs (NSAIDs), while quite effective in treating arthritic symptoms. are associated with gastrointestinal mucosal damage. Although therapy for patients with NSAID-induced ulcers or those at high risk of developing them is still a matter of debate, the current literature supports the use of misoprostol as the only drug effective for the prevention of both NSAID-induced gastric and duodenal ulceration. It has also been shown to treat NSAID-induced gastropathy in patients continuing their NSAID therapy. In a study of misoprostol (100 or 200 μg QID) plus NSAID, after three months of continuous therapy, a significantly lower frequency of gastric ulcers in the misoprostol-treated group was revealed: 100 μg misoprostol. 5.6%; 200 μg misoprostol, 1.4%; placebo, 21.7%. A recent threemonth, placebo-controlled study established the efficacy of misoprostol 200 μg QID in the prevention of NSAID-induced duodenal ulcers in 429 patients with osteoarthritis (OA), rheumatoid arthritis (RA), or other rheumatic disease, who were receiving daily treatment with various NSAIDs. The incidence of duodenal ulcer development over three months was 1.0% in patients treated with misoprostol versus 6.3% in placebo-treated patients (P = 0.004). The same trial also evaluated the efficacy of misoprostol 200 μg QID versus placebo in preventing NSAID-izduced gastric ulcers. The incidence of gastric ulcer over the threc-month treatment period was 1.5% in patients treated with misoprostol versus 9.0% in placebo-treated patients (P = 0.001).

Preliminary findings of a recent comparison of misoprostol (200 μg QID) and ranitidine (150 mg BID) given concurrently with NSAID therapy, clearly denionstrates thc superiority of misoprostol in preventing NSAID-induced gastric ulcers (≥ 0.3 cm in diameter). At the end of eight weeks. 1.1% of the misoprostol-treated patients developed gastric ulcer versus 5.2% of the ranitidine-treated paticnls (P = 0.003).

In another comparative trial, misoprostol (200 μg QID) and sucralfatc (1 gm QID) were coadministered with the NSAID therapy. The frequency of gastric ulcers (≥ 0.3 cm in diameter) at the end of three months was 1.6% in the misoprostol-treated group versus 16% in the sucrallatc-treated group (P ≥ 0.001).

Finally, the long-term efficacy of misoprostol in the prevention of NSAID-induced gastroduodenal lesions and ulcers was also evaluated. A 12-month, multicenter, randomized, double-blind, parallel group comparison trial was conducted. Misoprostol 200 μg (BID/TID) was coadministered with diclofenac 50 mg (RID/TID). Endoscopic evaluations were performed at 3, 6, and 12 months. Patients who developed clinically significant lesions (defined as oozing or intraluminal blood, > 10 erosions, ulceration or visible vessel) at 3 and 6 months were removed from the study. Endoscopic evaluation at 12 months showed that the incidence of gastroduodcnal ulccrs was 15% in the misoprostol group versus 31% in the placebo group (P = 0.018, Kaplan-Meier analysis).

Key Words:

• H₂-receptors
• ranitidine
• sucralfale
• misoprostol
• diclofenac
• omeprazole
• rheumatoid arthritis
• osteoarthritis