J Rheumatol Suppl

NSAID induced gastrointestinal complications: the ARAMIS perspective--1997. Arthritis, Rheumatism, and Aging Medical Information System.

Year 1998
Singh G. Rosen Ramey D.
Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
Gastrointestinal (GI) complications related to nonsteroidal antiinflammatory drug (NSAID) therapy are the most prevalent category of adverse drug reactions. Patients with arthritis are among the most frequent users of NSAID and are therefore particularly at risk for these side effects. To evaluate the nature of NSAID related GI complications and to determine how their frequency can be reduced, a series of studies of such complications in patients with rheumatic disease has been carried out based on data from the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). We review the literature and present findings from the ARAMIS studies. This report addresses whether GI side effects such as dyspepsia can serve as warning symptoms for serious GI complications and describes the risk factors for these life threatening complications. It also describes differences among NSAID with regard to their GI toxicity and describes a study that investigated whether H2-receptor antagonists and antacids affect the development of serious GI complications. In addition, ongoing research and topics to be addressed in future studies are described.

Prevention of gastrointestinal complications associated with nonsteroidal antiinflammatory drugs.

Year 1998
Agrawal NM. Aziz K.
Department of Medicine, University of Connecticut Health Center, Farmington 06032-1845, USA.
Nonsteroidal antiinflammatory drugs (NSAID), although used frequently for the treatment of arthritis and musculoskeletal disorders, may produce deleterious effects related to the gastrointestinal (GI) tract, including dyspeptic symptoms, erosions, ulcers, and serious GI complications (i.e., bleeding, perforation, and gastric outlet obstruction). Endoscopic studies with the synthetic prostaglandin E1 analog misoprostol, various acid-reducing agents (e.g., H2 receptor antagonists and proton pump inhibitors), and surface-active drugs such as sucralfate, have been shown to prevent NSAID induced gastric and/or duodenal ulcers. The Misoprostol Ulcer Complication Outcomes Safety Assessment (MUCOSA) trial was a 6 month, randomized, double blind, placebo controlled study to investigate whether concurrent administration of misoprostol would significantly reduce the occurrence of serious upper GI complications in patients with rheumatoid arthritis (RA) who were receiving NSAID. Results showed that overall complications were reduced by 40% (p = 0.049) among patients receiving misoprostol (25 patients with definite serious GI events among 4404 patients treated) compared with those receiving placebo (42 out of 4439 patients). Thus, cotherapy with misoprostol resulted in a statistically significant reduction in the incidence of serious NSAID induced upper GI complications compared with placebo in patients with RA.

Diclofenac/misoprostol: the European clinical experience.

Year 1998
McKenna F.
Trafford General Hospital, Davyhulme, Manchester, United Kingdom.
OBJECTIVE: The fixed combination of diclofenac sodium and misoprostol (Arthrotec) is the only nonsteroidal antiinflammatory drug (NSAID) that contains a gastroprotective component and is available in 2 formulations:(1) an enteric coated core of diclofenac sodium 50 mg surrounded by a mantle of misoprostol 200 microg, and (2) a 75 mg enteric coated diclofenac core also surrounded by a 200 microg mantle of misoprostol. This article reviews the European clinical experience with both formulations in patients with arthritis. METHODS: Three randomized, blinded, multicenter studies, including one in general practice, evaluated the efficacy of combination diclofenac/misoprostol versus diclofenac or ibuprofen in a total of 1824 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Four additional studies assessed antiarthritic efficacy and employed endoscopy to compare the gastroduodenal safety of combined diclofenac50/misoprostol with that of diclofenac, naproxen, piroxicam, or indomethacin in 1459 patients with RA, OA, or ankylosing spondylitis. The gastroduodenal safety and antiarthritic efficacy of diclofenac75/misoprostol was compared with that of diclofenac in one endoscopy study involving 514 patients with RA or OA. RESULTS: The efficacy and safety data obtained from these European clinical trials show that both formulations diclofenac50/misoprostol and diclofenac75/misoprostol are effective antiinflammatory drugs, with clinical efficacy equivalent to that of diclofenac. Diclofenac50/misoprostol is at least as effective as naproxen, piroxicam, indomethacin, and ibuprofen. Both formulations of the combination were associated with significantly fewer gastroduodenal ulcers compared with diclofenac. In separate studies, the tolerability of diclofenac50/misoprostol (as determined by withdrawal rates) was shown to be equivalent to that of diclofenac, naproxen, piroxicam, and ibuprofen, and the tolerability of diclofenac75/misoprostol was shown to be equivalent to that of diclofenac. The diclofenac50/misoprostol was associated with fewer decreases in hemoglobin concentration compared with diclofenac in the general practice study as well as in hospital patients. CONCLUSION: Diclofenac50/misoprostol and diclofenac75/misoprostol are effective in treating the signs and symptoms of RA and OA and are well tolerated by the majority of patients. Both of these formulations achieve a significant reduction in the incidence of both gastric and duodenal ulcers compared with other NSAID.