ABSTRACT
BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score =2), endoscopic remission, and quality of life were secondary outcomes. RESULTS: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare. CONCLUSIONS: Rosiglitazone was efficacious in the treatment of mild to moderately active UC.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Thiazolidinediones/therapeutic use , Administration, Oral , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Colitis, Ulcerative/pathology , Colonoscopy , Double-Blind Method , Drug Administration Schedule , Female , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/adverse effects , Humans , Male , Middle Aged , Patient Selection , Quality of Life , Rosiglitazone , Severity of Illness Index , Sigmoidoscopy , Thiazolidinediones/administration & dosage , Thiazolidinediones/adverse effects , Time Factors , Treatment Outcome , United StatesABSTRACT
Bowman-Birk inhibitor concentrate (BBIC), a soy extract with high protease inhibitor activity, is efficacious in the treatment of colitis in mice and has been used in numerous clinical trials. A randomized, double blind, placebo-controlled trial was performed to investigate the safety and possible benefits of BBIC in patients with active ulcerative colitis. The Sutherland Disease Activity Index (SDAI) was used to assess disease activity, response (Index decrease > or = 3), and remission (Index < or = 1 with no rectal bleeding) in patients receiving 12 weeks of therapy. The Index scores of patients receiving BBIC decreased more than those of the patients receiving placebo (P = 0.067). Beneficial trends were observed in the rates of remission (P = 0.082) and clinical response (P = 0.22). No severe adverse events were observed. This trial suggests a potential benefit over placebo for both achieving clinical response and induction of remission in patients with active ulcerative colitis without apparent toxicity.
Subject(s)
Colitis, Ulcerative/drug therapy , Trypsin Inhibitor, Bowman-Birk Soybean/therapeutic use , Trypsin Inhibitors/therapeutic use , Colitis, Ulcerative/diagnosis , Double-Blind Method , Follow-Up Studies , Humans , Remission Induction , Severity of Illness Index , Treatment OutcomeABSTRACT
OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine involved in the pathogenesis of inflammatory bowel disease. The monoclonal antibody to TNF-alpha, infliximab, is effective in treating Crohn's disease. Preclinical studies suggest the importance of TNF-alpha in treating ulcerative colitis (UC). We report the effectiveness of infliximab for UC and examine factors predictive of response to medication. METHODS: Data from all UC patients receiving infliximab at four institutions were analyzed. Disease activity was determined by the Disease Activity Index. RESULTS: A total of 27 patients with active UC received inpatient (37%) and outpatient (63%) infliximab as single (52%) or multiple (two to 15) infusions (48%). Twelve patients (44%) achieved remission and six patients (22%) had partial response. Nine patients had no response; five subsequently underwent total colectomy. The median time to achieve response and remission was 4 days and the median duration 8 wk. Nine of the 18 patients who responded experienced 19 relapses; 18 of these relapses (95%) were successfully treated with repeat infusions. Steroid-refractory patients were less likely to respond to infliximab therapy than were steroid-responsive patients (33% vs 83%; p = 0.026). No other factors were predictive of response to infliximab. Two patients developed serious adverse events, including death in one case. CONCLUSIONS: Preliminary evidence suggest effectiveness of infliximab in the treatment of UC, including medically refractory severe disease. Individuals who are refractory to corticosteroids, however, may be unlikely to respond to infliximab. A randomized controlled trial is necessary to further investigate the efficacy of infliximab in patients with UC.