Brian G Feagan1, John W D McDonald2, Remo Panaccione3, Robert A Enns4, Charles N Bernstein5, Terry P Ponich6, Raymond Bourdages7, Donald G Macintosh8, Chrystian Dallaire9, Albert Cohen10, Richard N Fedorak11, Pierre Paré12, Alain Bitton13, Fred Saibil14, Frank Anderson15, Allan Donner16, Cindy J Wong2, Guangyong Zou16, Margaret K Vandervoort2, Marybeth Hopkins2, Gordon R Greenberg17. 1. Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. Electronic address: brian.feagan@robartsinc.com. 2. Robarts Clinical Trials, Western University, London, Ontario, Canada. 3. Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Alberta, Canada. 4. St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. 5. Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada. 6. Department of Medicine, Western University, London, Ontario, Canada; London Health Sciences Centre, South Street Hospital, London, Ontario, Canada. 7. Hôtel-Dieu de Lévis, Lévis, Quebec, Canada. 8. Dalhousie University, Halifax, Nova Scotia, Canada. 9. Centre Hospitalier Universitaire de Québec-Pavillon St. François d'Assise, Quebec City, Quebec, Canada. 10. Jewish General Hospital, Montreal, Quebec, Canada. 11. University of Alberta, Edmonton, Alberta, Canada. 12. Hôpital St. Sacrement, Quebec City, Quebec, Canada. 13. McGill University Health Centre, Montreal, Quebec, Canada. 14. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 15. The Liver and Intestinal Research Centre, Vancouver, British Columbia, Canada. 16. Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. 17. Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND & AIMS:Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone. METHODS: In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50. RESULTS: Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated. CONCLUSIONS: The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment withprednisone. ClincialTrials.gov number, NCT00132899.
RCT Entities:
BACKGROUND & AIMS:Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone. METHODS: In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50. RESULTS:Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated. CONCLUSIONS: The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment with prednisone. ClincialTrials.gov number, NCT00132899.
Authors: Edward L Barnes; Alison Goldin; Rachel W Winter; Emily Collins; Bonnie Cao; Madeline Carrellas; Anne Marie Crowell; Joshua R Korzenik Journal: Dig Dis Sci Date: 2016-09-17 Impact factor: 3.199
Authors: Douglas L Nguyen; Sarah Flores; Kareem Sassi; Matthew L Bechtold; Emily T Nguyen; Nimisha K Parekh Journal: Ther Adv Chronic Dis Date: 2015-05 Impact factor: 5.091