arbaprostil and Arthritis--Rheumatoid

Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aluminum Hydroxide; Anti-Inflammatory Agents, Non-Steroidal; Arbaprostil; Arthritis, Rheumatoid; Aspirin; Female; Gastric Mucosa; Humans; Male; Middle Aged; Multicenter Studies as Topic; Osteoarthritis; Placebos; Prostaglandins E, Synthetic; Randomized Controlled Trials as Topic; Stomach Diseases; Stomach Ulcer

Thirteen patients who had rheumatoid arthritis and gastroduodenal lesion (erosions, ulcers) received 200 micrograms/d of 15(R)-15-methyl prostaglandin E2 (MPGE2) for one month in a controlled, randomized, double-blind crossover study. The patients continued their usual arthritis medications. Serial assessments were made with endoscopy and multiple antral biopsies. Seven patients improved on MPGE2 and 3 improved on placebo. Two patients worsened on MPGE2 compared with 3 on placebo. No dramatic benefit was observed after one month of therapy with MPGE2, although a moderate benefit could have been missed in a small study of this type. Our experience with this study suggests that future studies in rheumatoid arthritis should first establish the natural history of lesions in a given group of patients, that a cross-over design may actually hamper interpretation and that therapy should be more prolonged.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arbaprostil; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Gastrointestinal Hemorrhage; Humans; Middle Aged; Prostaglandins E, Synthetic

Topics: Adult; Aged; Arbaprostil; Arthritis, Rheumatoid; Aspirin; Female; Gastric Mucosa; Gastritis; Humans; Indomethacin; Male; Middle Aged; Prostaglandins E, Synthetic