527-533DOI: 10.17235/reed.2015.3804/2015
LUIS FERNÁNDEZ SALAZAR, Jesús Barrio Andrés, Fernando Muñoz, Concepción Muñoz Rosas, Ramón Pajares Villarroya, MONTSERRAT RIVERO TIRADO, Vanessa Prieto Vicente, Jesús Legido Gil, Abdel Bouhmidi, Maite Herranz, Guillermo González Redondo, Nereida Fernández Fernández, fernando santos santamarta, Ramón Sánchez Ocaña, Diana Joao Matias,
Abstract
INTRODUCTION: IFX therapy intensification in UC is more common than established in pivotal studies. OBJECTIVES: To establish the frequency and form of intensification for UC in clinial practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment. METHODS: A retrospective study of 10 hospitals and 144 patients with response to IFX induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy. RESULTS: Follow-up time from induction to data collection: 38 months (IQR, 20-62). Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent IMM and IFX initiation was an independent predictor of intensification (HR, 0.034; p, 0.006; CI, 0.003-0.371). In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs 10.2%; p, 0.002), steroid reintroduction (35% vs 18%; p, 0.018), and colectomy (22% vs 6.4%; p, 0.011) were more common. Of patients on intensification 17% returned to receiving 5 mg/kg every 8 weeks. CONCLUSIONS: Intensification is common and occasionally reversible. IMM intiation at the time of induction with IFX predicts non-intensification. Intensification, while effective, is associated with poorer outcome.
New comment
Comments
No comments for this article
References
1. Reinisch W, Sandborn WJ, Rutgeerts P, et al. Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies. Inflamm Bowel Dis 2012;18: 201-11.
2. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353: 2462-76.
3. Taxonera C, Olivares D, Mendoza JL, et al. Need for infliximab dose intensification in Crohn's disease and ulcerative colitis. World J Gastroenterol 2014, 20: 9170-7.
4. Barreiro-de Acosta M, Lorenzo A, Mera J, et al. Mucosal healing and steroid-sparing associated with infliximab for steroid-dependent ulcerative colitis. J Crohns Colitis 2009; 3: 271-6.
5. Cesarini M, Katsanos K, Papamichael K, et al. Dose optimization is effective in ulcerative colitis patients losing response to infliximab: a collaborative multicentre retrospective study. Dig Liver Dis 2014; 46: 135-9.
6. Yamada S, Yoshino T, Matsuura M, et al. Long-term efficacy of infliximab for refractory ulcerative colitis: results from a single center experience. BMC Gastroenterol 2014; 14: 80.
7. Vahabnezhad E, Rabizadeh S, Dubinsky MC. A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2014; 20: 606-13.
8. Paul S, Del Tedesco E, Marotte H, et al. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis 2013; 19: 2568-76.
9. Perez-Pitarch A, Ferriols-Lisart R, Alos-Alminana M, et al. A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients. Rev Esp Enferm Dig 2015; 107:137-42.
10. Ferrante M, Vermeire S, Fidder H, et al. Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis 2008; 2: 219-25.
11. Oussalah A, Evesque L, Laharie D, et al. A multicenter experience with infliximab for ulcerative colitis: outcomes and predictors of response, optimization, colectomy, and hospitalization. Am J Gastroenterol 2010; 105:2617-25.
12. Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012; 10: 391-9.
13. Lee KM, Jeen YT, Cho JY, et al. Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: a Korean multicenter retrospective study. J Gastroenterol Hepatol 2013; 28:1829-33.
14. Armuzzi A, Pugliese D, Danese S, et al. Long-term combination therapy with infliximab plus azathioprine predicts sustained steroid-free clinical benefit in steroid-dependent ulcerative colitis. Inflamm Bowel Dis 2014;20: 1368-74.
15. Lichtenstein GR, Diamond RH, Wagner CL, et al. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 2009; 30:210-26.
16. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014; 146:392-400.
17. Ungar B, Chowers Y, Yavzori M, et al. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut 2014; 63:1258-64.
1. Reinisch W, Sandborn WJ, Rutgeerts P, et al. Long-term infliximab maintenance therapy for ulcerative colitis: The ACT-1 and -2 extension studies. Inflamm Bowel Dis 2012;18:201-11. DOI: 10.1002/ibd.21697
2. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-76. DOI: 10.1056/NEJMoa050516
3. Taxonera C, Olivares D, Mendoza JL, et al. Need for infliximab dose intensification in Crohn's disease and ulcerative colitis. World J Gastroenterol 2014;20:9170-7.
4. Barreiro-de Acosta M, Lorenzo A, Mera J, et al. Mucosal healing and steroid-sparing associated with infliximab for steroid-dependent ulcerative colitis. J Crohns Colitis 2009;3:271-6. DOI: 10.1016/j.crohns.2009.06.003
5. Cesarini M, Katsanos K, Papamichael K, et al. Dose optimization is effective in ulcerative colitis patients losing response to infliximab: A collaborative multicentre retrospective study. Dig Liver Dis 2014;46:135-9. DOI: 10.1016/j.dld.2013.10.007
6. Yamada S, Yoshino T, Matsuura M, et al. Long-term efficacy of infliximab for refractory ulcerative colitis: Results from a single center experience. BMC Gastroenterol 2014;14:80. DOI: 10.1186/1471-230X-14-80
7. Vahabnezhad E, Rabizadeh S, Dubinsky MC. A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2014;20:606-13. DOI: 10.1097/MIB.0000000000000003
8. Paul S, Del Tedesco E, Marotte H, et al. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: A prospective study. Inflamm Bowel Dis 2013;19:2568-76. DOI: 10.1097/MIB.0b013e3182a77b41
9. Perez-Pitarch A, Ferriols-Lisart R, Alos-Alminana M, et al. A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients. Rev Esp Enferm Dig 2015;107:137-42.
10. Ferrante M, Vermeire S, Fidder H, et al. Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis 2008;2:219-25. DOI: 10.1016/j.crohns.2008.03.004
11. Oussalah A, Evesque L, Laharie D, et al. A multicenter experience with infliximab for ulcerative colitis: Outcomes and predictors of response, optimization, colectomy, and hospitalization. Am J Gastroenterol 2010;105:2617-25. DOI: 10.1038/ajg.2010.345
12. Hyams J, Damaraju L, Blank M, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012;10:391-9. DOI: 10.1016/j.cgh.2011.11.026
13. Lee KM, Jeen YT, Cho JY, et al. Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: A Korean multicenter retrospective study. J Gastroenterol Hepatol 2013;28:1829-33. DOI: 10.1111/jgh.12324
14. Armuzzi A, Pugliese D, Danese S, et al. Long-term combination therapy with infliximab plus azathioprine predicts sustained steroid-free clinical benefit in steroid-dependent ulcerative colitis. Inflamm Bowel Dis 2014;20:1368-74. DOI: 10.1097/MIB.0000000000000115
15. Lichtenstein GR, Diamond RH, Wagner CL, et al. Clinical trial: Benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 2009;30:210-26. DOI: 10.1111/j.1365-2036.2009.04027.x
16. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014;146:392-400. DOI: 10.1053/j.gastro.2013.10.052
17. Ungar B, Chowers Y, Yavzori M, et al. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut 2014;63:1258-64. DOI: 10.1136/gutjnl-2013-305259