Genetic predictors of patient response and side effects in the treatment of rheumatoid arthritis with a high dose nonsteroidal antiinflammatory drug regimen

Abstract

Clinical, laboratory, genetic, and radiologic studies were evaluated for 18 patients with rheumatoid arthritis who were treated for a mean of 16.6 months with a regimen involving supplementary aspirin and piroxicam, an investigational, nonsteroidal antiinflammatory agent. Although improvement in disease activity was seen, progression was evident on successive radiographs. Disease activity was not associated with the presence of any of the genetic markers. Peptic ulcers developed in 33% of patients, all of whom had type 0 blood. ABO blood typing may therefore be useful in patients with rheumatoid arthritis before consideration of therapy with potentially ulcerogenic drugs.In rheumatoid arthritis, recent evidence has suggested that the characterization of certain genetic factors, such as human leukocyte antigens (HLA), A 3 0 blood groups, and alpha-I-antitrypsin phenotypes, may be useful in predicting the severity of PATIENTS AND METHODSIn an open-label study, 45 patients, ages 21-65 years, with rheumatoid arthritis categorized as functional class I1 or 111 according to criteria of the American Rheumatism Association (4), took between 20 and 40 mg of piroxicam daily for up to 946 days (5). Patients with active ulcer disease were excluded by a preliminary upper gastrointestinal barium roentgenogram. Patients who developed gastrointestinal symptoms suggestive of ulcer disease underwent additional radiologic study. Maintenance doses of gold, prednisone (510 mg/day), and small doses of aspirin were allowed but carefully recorded. For 3 months, patients were evaluated with safety and articular checks every 2 weeks; thereafter, the checks were at monthly intervals. Patient and observer assessments, the latex agglutination test, grip strength, joint count, and the Westergren erythrocyte sedimentation rate comprised a cumulative grading method, the Modified Rheumatoid Activity Index (6). This index was calculated by expressing the raw scores of the 6 parameters as percentages, adding them together, and multiplying the sum by y6.The minimum score possible was 0, the maximum, 245 (6). Joint counts were graded 1 (subjective tenderness only), 2 (wincing), and 3 (wincing plus withdrawal) in 76 joints; the maximum possible score was 228.

The Interleukin‐1 RN Polymorphism and Helicobacter pylori Infection in the Development of Duodenal Ulcer

“…Specific host characteristics that may determine susceptibility to H. pylori ‐associated diseases include gender, human leukocyte antigen genotypes, blood groups, gastric acid physiology and interleukin‐1 ( IL‐1 ) locus polymorphism [13,14]. Blood group O has traditionally been associated with the risk of developing duodenal ulcer (DU) [15,16]. Boren et al [17] recently demonstrated that the blood group Lewis b possessed receptors for H. pylori , and it was exposed only in individuals with blood group O.…”