[en] Background: Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%-25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM. Methods: We included 231 consecutive patients from 10 Belgian centers initiating ADM treatment for active UC before September 1, 2015 (follow-up >/=1 year in each patient). We performed detailed chart review to identify variables associated with short-term clinical benefit (based on physician global assessment and absence of rectal bleeding at week 10), success of dose escalation, and dose de-escalation. Backward Cox regression and Wald Logistic regression were used to identify predictive variables. Results: Short-term clinical benefit was achieved in 101 patients (44%) and was less frequent in infliximab failures [37% vs 50%, Odds ratio 0.57 (95% CI 0.34-0.97), P = 0.038]. After a median of 2.8 (1.7-5.1) months, 164 patients (71%) needed ADM discontinuation (n = 35, 15%) or dose escalation (n = 129, 56%). Dose escalation was successful in 77/129 (60%). Dose de-escalation was attempted in 71% (55/77) after a median of 4.3 (2.9-7.2) months and was successful in 80% (43/54). Conclusions: In this cohort, 56% of patients with UC required ADM dose escalation with a 60% success rate. Of note, most patients could be successfully de-escalated later on.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Van de Vondel, Saartje
Baert, Filip
Vanden Branden, Stijn
Amininejad, Leila
Dewint, Pieter
Van Moerkercke, Wouter
Rahier, Jean-Francois
Hindryckx, Pieter
Bossuyt, Peter
Ferrante, Marc
Reenaers, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive
Other collaborator :
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Language :
English
Title :
Incidence and Predictors of Success of Adalimumab Dose Escalation and De-escalation in Ulcerative Colitis: a Real-World Belgian Cohort Study.
Publication date :
2018
Journal title :
Inflammatory Bowel Diseases
ISSN :
1078-0998
eISSN :
1536-4844
Publisher :
Lippincott Williams & Wilkins, United States - Maryland
Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006; 3: 390-407.
Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007; 369: 1627-40.
Mowat C, Cole A, Windsor A, et al.; IBD Section of the British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011; 60: 571-607.
Van Assche G, Vermeire S, Rutgeerts P. Management of acute severe ulcerative colitis. Gut. 2011; 60: 130-3.
Magro F, Gionchetti P, Eliakim R, et al.; European Crohn's and Colitis Organisation [ECCO]. Third european evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis. 2017; 11: 649-70.
Billiet T, Rutgeerts P, Ferrante M, et al. Targeting TNF for the treatment of inflammatory bowel disease. Expert Opin Biol Ther. 2014; 14: 75-101.
Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011; 60: 780-7.
Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012; 142: 257-65.
Billioud V, Sandborn WJ, Peyrin-Biroulet L. Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review. Am J Gastroenterol. 2011; 106: 674-84.
Baert F, Glorieus E, Reenaers C, et al.; BIRD (Belgian IBD Research and Development). Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients. J Crohns Colitis. 2013; 7: 154-60.
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987; 317: 1625-9.
den Broeder AA, van Herwaarden N, van der Maas A, et al. Dose reduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non inferiority trial, the DRESS study. BMC Musculoskelet Disord. 2013; 14: 299.
Van Steenbergen S, Bian S, Vermeire S, et al. Dose de-escalation to adalimumab 40 mg every 3 weeks in patients with Crohn's disease-A nested case-control study. Aliment Pharmacol Ther. 2017; 45: 923-32.
Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015; 148: 1320-9.
West RL, Zelinkova Z, Wolbink GJ, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther. 2008; 28: 1122-6.
Chaparro M, Panes J, Garcia V, et al. Long-term durability of response to adalimumab in Crohn's disease. Inflamm Bowel Dis. 2012; 18: 685-90.
Karmiris K, Paintaud G, Noman M, et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn's disease. Gastroenterology. 2009; 137: 1628-10.
Colombel JF, Sandborn WJ, Reinisch W, et al.; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010; 362: 1383-95.
Panaccione R, Ghosh S, Middleton S, et al. Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: The UC SUCCESS trial. J Crohns Colitis. 2011; 5: S8.
Karmiris K, Paintaud G, Degenne D, et al. Antibodies against adalimumab in Crohn's disease patients who failed infliximab treatment: correlation with clinical response and trough serum levels. Gut. 2008; 57: A67.
Reenaers C, Louis E, Belaiche J, et al. Does co-treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumab? Aliment Pharmacol Ther. 2012; 36: 1040-8.
Cosnes J, Sokol H, Bourrier A, et al. Adalimumab or infliximab as monotherapy, or in combination with an immunomodulator, in the treatment of Crohn's disease. Aliment Pharmacol Ther. 2016; 44: 1102-13.
Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 montreal world congress of gastroenterology. Can J Gastroenterol. 2005; 19(Suppl A): 5A-36A.