Z Gastroenterol 2014; 52(2): 204-211
DOI: 10.1055/s-0033-1355818
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Adalimumab in der Behandlung der Colitis ulcerosa – ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie

Adalimumab for the Treatment of Ulcerative Colitis – A Consensus Report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology
G. Novacek
1   Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Gastroenterologie und Hepatologie, Wien, Österreich
,
C. Dejaco
1   Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Gastroenterologie und Hepatologie, Wien, Österreich
,
P. Knoflach
2   Klinikum Wels, 1. Interne Abteilung, Wels, Österreich
,
A. Moschen
3   Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin I, Innsbruck, Österreich
,
W. Petritsch
4   Medizinische Universität Graz, Universitätsklinik für Innere Medizin, Klinische Abteilung für Gastroenterologie und Hepatologie, Graz, Österreich
,
H. Vogelsang
1   Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Gastroenterologie und Hepatologie, Wien, Österreich
,
W. Reinisch
1   Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Gastroenterologie und Hepatologie, Wien, Österreich
› Author Affiliations
Further Information

Publication History

06 July 2013

27 September 2013

Publication Date:
31 January 2014 (online)

Zusammenfassung

TNF-alpha-Antikörper haben den Verlauf der mittelschweren bis schweren aktiven Colitis ulcerosa wesentlich verbessert. Adalimumab ist der erste vollständig humane, monoklonale TNF-alpha-Antikörper, den Patienten selbst subkutan applizieren können. Adalimumab ist seit April 2012 zur Behandlung der mittelschweren bis schweren, aktiven Colitis ulcerosa bei Patienten zugelassen, bei denen mit einer adäquaten Therapie mit einem Glukokortikoid und einem Immunsuppressivum kein ausreichendes Ansprechen erzielt werden konnte, oder die eine entsprechende Unverträglichkeit aufweisen oder bei denen diese Therapien kontraindiziert sind. Mit Adalimumab können verglichen mit Placebo bei Patienten mit mittelschwerer bis schwerer aktiver Colitis ulcerosa häufiger eine klinische Remission und eine mukosale Heilung induziert und aufrechterhalten werden, die Zahl der Colitis ulcerosa-bedingten Krankenhausaufenthalte verringert sowie die gesundheitsbezogene Lebensqualität verbessert werden. Der Wirkungseintritt kann bereits nach 2 Wochen der Therapie erfolgen. Die Sicherheitsdaten von Adalimumab entsprechen weitgehend jenen anderer TNF-alpha-Blocker. In den bisher publizierten Studien zum Einsatz von Adalimumab bei Colitis ulcerosa wurden keine neuen Sicherheitsfragen aufgeworfen. Der vorliegende Konsensusbericht der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) fasst die aktuelle Datenlage zu Adalimumab in der Behandlung der Colitis ulcerosa zusammen und soll als praktischer Leitfaden für die Anwendung von Adalimumab bei Patienten mit Colitis ulcerosa dienen.

Abstract

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.

 
  • Literatur

  • 1 Dignass A, Lindsay JO, Sturm A et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis 2012; 6: 991-1030
  • 2 Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med 2011; 365: 1713-1725
  • 3 Sartor RB. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 1994; 106: 533-539
  • 4 Braegger CP, Nicholls S, Murch SH et al. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339: 89-91
  • 5 Murch SH, Braegger CP, Walker-Smith JA et al. Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease. Gut 1993; 34: 1705-1709
  • 6 Murch SH, Lamkin VA, Savage MO et al. Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut 1991; 32: 913-917
  • 7 Austria Codex Fachinformation: Humira® 40mg Injektionslösung in Fertigspritze. (Stand der Information: Februar 2013).
  • 8 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: 780-787
  • 9 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: 257-265
  • 10 Novacek G, Haas T, Knoflach P et al. Adalimumab in der Behandlung des adulten Morbus Crohn – Update eines Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (Adalimumab for the treatment of adult Crohn’s disease – update of a Consensus Report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology). Z Gastroenterol 2013; 51: 1101-1109
  • 11 Afif W, Leighton JA, Hanauer SB et al. Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab. Inflamm Bowel Dis 2009; 15: 1302-1307
  • 12 Barreiro-de AcostaM, Lorenzo A, Dominguez-Munoz JE. Adalimumab in ulcerative colitis: two cases of mucosal healing and clinical response at two years. World J Gastroenterol 2009; 15: 3814-3816
  • 13 Peyrin-Biroulet L, Laclotte C, Roblin X et al. Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: an open-label study. World J Gastroenterol 2007; 13: 2328-2332
  • 14 Colombel JF, Sandborn W, Wolf D et al. Long-term efficacy of adalimumab for treatment of moderately to severely active ulcerative colitis. Inflamm Bowel Dis 2012; 18: S20-S21
  • 15 Taxonera C, Estelles J, Fernandez-Blanco I et al. Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment Pharmacol Ther 2011; 33: 340-348
  • 16 McDermott E, Murphy S, Keegan D et al. Efficacy of Adalimumab as a long term maintenance therapy in ulcerative colitis. J Crohns Colitis 2013; 7: 150-153
  • 17 Oussalah A, Laclotte C, Chevaux JB et al. Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience. Aliment Pharmacol Ther 2008; 28: 966-972
  • 18 Gies N, Kroeker KI, Wong K et al. Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort. Aliment Pharmacol Ther 2010; 32: 522-528
  • 19 Sandborn WJ, Colombel JF, D'Haens G et al. One-year maintenance outcomes among patients with moderatly-to-severly active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2. Aliment Pharmacol Ther 2013; 37: 204-213
  • 20 Reinisch W, Sandborn WJ, Panaccione R et al. 52-Week efficacy of adalimumab in patients with moderately to severely active ulcerative colitis who failed corticosteroids and/or immunosuppressants. Inflamm Bowel Dis 2013; 19: 1700-1709
  • 21 Wolf D, D'Haens G, Sandborn WJ et al. Rate of and response to dose escalation in patients treated with adalimumab for moderately to severely active ulcerative colitis: subanalysis of ULTRA 2. Am J Gastroenterol 2012; 107: S619
  • 22 D'Haens G, Sandborn WJ, Feagan BG et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 2007; 132: 763-786
  • 23 Peyrin-Biroulet L, Ferrante M, Magro F et al. Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal healing on the course of inflammatory bowel disease. J Crohns Colitis 2011; 5: 477-483
  • 24 Colombel JF, Rutgeerts P, Reinisch W et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 2011; 141: 1194-1201
  • 25 Parente F, Molteni M, Marino B et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis? A prospective study. Am J Gastroenterol 2010; 105: 1150-1157
  • 26 Rutgeerts P, Sandborn WJ, Feagan BG et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005; 353: 2462-2476
  • 27 Ardizzone S, Cassinotti A, Duca P et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol 2011; 9: 483-489
  • 28 Frøslie KF, Jahnsen J, Moum BA et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007; 133: 412-422
  • 29 Ferrante M, Vermeire S, Fidder H et al. Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis 2008; 2: 219-225
  • 30 Sandborn WJ, Rutgeerts P, Feagan BG et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009; 137: 1250-1260
  • 31 Rutter M, Saunders B, Wilkinson K et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 2004; 126: 451-459
  • 32 Bitton A, Peppercorn MA, Antonioli DA et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 2001; 120: 13-20
  • 33 D'Haens G, Van Assche G, Wolf D et al. Mucosal healing in ulcerative colitis patients with week 8 response to adalimumab: subanalysis of ULTRA 2. Inflamm Bowel Dis 2012; 18: S21
  • 34 Armuzzi A, Biancone L, Daperno M et al. Adalimumab in active ulcerative colitis: A “real-life” observational study. Dig Liver Dis 2013; (epub ahead of print)
  • 35 Leonard P, Yang M, Chao J et al. Complications associated with colectomy in patients with ulcerative colitis. Gastroenterology 2012; 142: S-401
  • 36 Loftus Jr EV, Leonard P, Yang M et al. A retrospective study of colectomy complications and their associated costs for patients with ulcerative colitis. Gastroenterology 2012; 142: S-198
  • 37 Sandborn WJ, Van Assche GA, Thakkar R et al. Adalimumab Improves Health-Related Quality of Life for 52 Weeks in Patients With Ulcerative Colitis. Gastroenterology 2011; 140: S-263
  • 38 Sandborn WJ, Colombel JF, Yang M et al. Sustained clinical remission of ulcerative colitis is associated with greater improvements in quality of life, work productivity and activity. Am J Gastroenterol 2011; 106: S 456
  • 39 Van Assche G, Wolf D, D'Haens G et al. Reduced steroid usage in ulcerative colitis patients with week 8 response to adalimumab: subanalysis of ULTRA 2. Am J Gastroenterol 2012; 107: S611
  • 40 Feagan BG, Sandborn WJ, Skup M et al. Adalimumab therapy reduces hospitalization and colectomy rates in patients with ulcerative colitis among initial responders. Am J Gastroenterol 2012; 107: S642
  • 41 Feagan BG, Sandborn WJ, Thakkar RB et al. Adalimumab induction dose reduces the risk of hospitalizations and colectomies in patients with ulcerative colitis during the first 8 weeks of therapy. Am J Gastroenterol 2012; 107: S647
  • 42 Colombel JF, Thakkar RB, Robinson AM et al. Comparative colorectal cancer risk in patients with ulcerative colitis treated with adalimumab versus conventional therapy. Am J Gastroenterol 2012; 107: S645
  • 43 Waterman M, Xu W, Dinani A et al. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease. Gut 2013; 62: 387-394
  • 44 Nørgard BM, Nielsen J, Qvist N et al. Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with ulcerative colitis – a nationwide cohort study. Aliment Pharmacol Ther 2012; 35: 1301-1309
  • 45 Yang Z, Wu Q, Wang F et al. Meta-analysis: effect of preoperative infliximab use on early postoperative complications in patients with ulcerative colitis undergoing abdominal surgery. Aliment Pharmacol Ther 2012; 36: 922-928
  • 46 Appau KA, Fazio VW, Shen B et al. Use of infliximab within 3 months of ileocolonic resection is associated with adverse postoperative outcomes in Crohn’s patients. J Gastrointest Surg 2008; 12: 1738-1744
  • 47 Kopylov U, Ben-Horin S, Zmora O et al. Anti-tumor necrosis factor and postoperative complications in Crohn’s disease: systematic review and meta-analysis. Inflamm Bowel Dis 2012; 18: 2404-2413
  • 48 Syed A, Cross RK, Flasar MH. Anti-tumor necrosis factor therapy is associated with infections after abdominal surgery in Crohn’s disease patients. Am J Gastroenterol 2013; 108: 583-593
  • 49 Narula N, Charleton D, Marshall JK. Meta-analysis: peri-operative anti-TNFalpha treatment and post-operative complications in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 37: 1057-1064
  • 50 Jürgens M, Brand S, Filik L et al. Safety of adalimumab in Crohn's disease during pregnancy: case report and review of the literature. Inflamm Bowel Dis 2010; 16: 1634-1636
  • 51 Schnitzler F, Fidder H, Ferrante M et al. Outcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy. Inflamm Bowel Dis 2011; 17: 1846-1854
  • 52 Kane SV, Acquah LA. Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol 2009; 104: 228-233
  • 53 Mahadevan U, Wolf DC, Dubinsky M et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11: 286-292
  • 54 Zelinkova Z, van der Ent C, Bruin KF et al. Effects of discontinuing anti-tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure. Clin Gastroenterol Hepatol 2013; 11: 318-321
  • 55 Traussnigg S, Eser A, Primas C et al. Adalimumab (ADA) and infliximab (IFX) therapy during pregnancy in IBD: a prospective assessment of outcome, safety and cord blood levels. J Crohns Colitis 2013; 7: S252-S253
  • 56 Ben-Horin S, Yavzori M, Katz L et al. Adalimumab level in breast milk of a nursing mother. Clin Gastroenterol Hepatol 2010; 8: 475-476