Infliximab plus azathioprine is more effective than azathioprine alone in achieving mucosal healing in pediatric patients with Crohn's disease
Language English Country Australia Media print
Document type Journal Article
Grant support
Research Grant [SVV 260396]
Univerzita Karlova v Praze
- Keywords
- azathioprine, combined immunosuppression, infliximab, mucosal healing, pediatric Crohnʼs disease,
- MeSH
- Azathioprine therapeutic use MeSH
- Crohn Disease * drug therapy MeSH
- Child MeSH
- Immunosuppressive Agents MeSH
- Infliximab therapeutic use MeSH
- Humans MeSH
- Pediatrics * MeSH
- Retrospective Studies MeSH
- Drug Synergism MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Azathioprine MeSH
- Immunosuppressive Agents MeSH
- Infliximab MeSH
OBJECTIVES: Over the past few years, mucosal healing (MH) has emerged as a promising goal in the treatment of pediatric patients with Crohn's disease (CD). We aimed to assess whether combination therapy with infliximab (IFX) + azathioprine (AZA) was more effective than AZA therapy alone in achieving mucosal healing in pediatric patients with CD. METHODS: Newly diagnosed pediatric patients with CD at the Department of Pediatrics in University Hospital in Hradec Králové were retrospectively recruited (2000-2014). The patients were divided into two groups according to the therapy: (a) IFX + AZA ± corticosteroids ± 5-aminosalicylic acid (5-ASA) (n = 16); and (b) AZA ± corticosteroids ± 5-ASA (n = 40). The patients were also divided into two groups: "MH" and "no MH," according to their MH status. MH was defined as the complete endoscopic disappearance of all mucosal ulcerations (including aphthous ulcerations) and the absence of any sign of mucosal inflammation in the terminal ileum and the large bowel. RESULTS: Of 56 patients, MH was observed in 56% (9/16) treated with combined therapy in comparison with 15% (6/40) of patients in the AZA group (P = 0.006). The median dose of AZA in both groups was 2.1 mg/kg per day. We observed eight adverse events in seven patients from the IFX + AZA group. Adverse effects were less common in the AZA group (P = 0.002). CONCLUSION: Combined therapy (IFX + AZA) was more effective in achieving MH in pediatric CD than treatment with AZA alone.
See more in PubMed
Peyrin-Biroulet L, Reinisch W, Colombel JF, et al. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohnʼs disease in the SONIC trial. Gut. 2014;63(1):88-95.
Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohnʼs disease. Inflamm Bowel Dis. 2009;15(9):1295-1301.
D'Haens G, Noman M, Baert F. Endoscopic healing after infliximab treatment for Crohn's disease provides a longer time to relapse. Gastroenterology; 2002; 122.
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383-1395.
Peyrin-Biroulet L, Sandborn W, Sands B, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110(9):1324-1338.
Rutgeerts P, Geboes K, Vantrappen G, Kerremans R, Coenegrachts J, Coremans G. Natural history of recurrent Crohnʼs disease at the ileocolonic anastomosis after curative surgery. Gut. 1984;25(6):665-672.
Mary J-Y, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30(7):983-989.
Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
Vuitton L, Marteau P, Sandborn WJ, et al. IOIBD technical review on endoscopic indices for Crohn's disease clinical trials. Gut. 2016;65(9):1447-1455.
Villanacci V, Antonelli E, Geboes K, Casella G, Bassotti G. Histological healing in inflammatory bowel disease: a still unfulfilled promise. World J Gastroenterol. 2013;19(7):968-978.
Rutgeerts P, Diamond RH, Bala M, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease. Gastrointest Endosc. 2006;63(3):433-442.
Olbjorn C, Nakstad B, Smastuen MC, Thiis-Evensen E, Vatn MH, Perminow G. Early anti-TNF treatment in pediatric Crohn's disease. Predictors of clinical outcome in a population-based cohort of newly diagnosed patients. Scand J Gastroenterol. 2014;49(12):1425-1431.
Kierkuś J, Iwańczak B, Wegner A, et al. Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn's disease. J Pediatr Gastroenterol Nutr. 2015;60(5):580-585.
Nuti F, Civitelli F, Bloise S, et al. Prospective evaluation of the achievement of mucosal healing with anti-TNF-alpha therapy in a paediatric Crohn's disease cohort. J Crohns Colitis. 2016;10(1):5-12.
Kang B, Choi SY, Kim HS, Kim K, Lee YM, Choe YH. Mucosal healing in paediatric patients with moderate-to-severe luminal Crohn's disease under combined immunosuppression: escalation versus early treatment. J Crohns Colitis. 2016;10(11):1279-1286.
Lee YM, Kang B, Lee Y, Kim MJ, Choe YH. Infliximab “top-down” strategy is superior to “step-up” in maintaining long-term remission in the treatment of pediatric Crohnʼs disease. J Pediatr Gastroenterol Nutr. 2015;60(6):737-743.
IBD working group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis - the Porto criteria. J Pediatr Gastroenterol Nutr. 2005;41(1):1-7.
Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011;17(6):1314-1321.
Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn's-disease activity index. J Pediatr Gastroenterol Nutr. 1991;12(4):439-447.
Nobile S, Gionchetti P, Rizzello F, Calabrese C, Campieri M. Mucosal healing in pediatric Crohn's disease after anti-TNF therapy: a long-term experience at a single center. Eur J Gastroenterol Hepatol. 2014;26(4):458-465.
Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology. 2010;138(2):463-468.
Santha SL, Shankar PR, Pan A, Schoen B, Kugathasan S, Sauer CG. Mucosal healing in clinical practice: a single-center pediatric IBD experience. Inflamm Bowel Dis. 2017;23(8):1447-1453.
Shah SC, Colombel JF, Sands BE, Narula N. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease. Aliment Pharmacol Ther. 2016;43(3):317-333.
Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9(1):36-41.e1.
Colombel JF, Loftus EV, Tremaine WJ, et al. The safety profile of infliximab in patients with Crohnʼs disease: the Mayo Clinic experience in 500 patients. Gastroenterology. 2004;126(1):19-31.
Cozijnsen MA, Escher JC, Griffiths A, Turner D, de Ridder L. Benefits and risks of combining anti-tumor necrosis factor with immunomodulator therapy in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(4):951-961.
Lemaitre M, Kirchgesner J, Rudnichi A, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017;318(17):1679-1686.