Infliximab in der Therapie des Morbus Crohn – ein praktischer Leitfaden: aktualisierter ÖGGH-Konsensus der Arbeitsgruppe Chronisch-entzündliche Darmerkrankungen der ÖGGH

Zusammenfassung

Infliximab ist ein monoklonaler Antikörper gegen Tumor-Nekrose-Faktor-alpha (TNF-α), der für die Therapie chronisch entzündlicher Darmerkrankungen (CED) wie Morbus Crohn (MC), Morbus Crohn mit Fistelbildung (MCF), Colitis ulcerosa (CU) und pädiatrischen Morbus Crohn (pädMC) ab 6 Jahren zugelassen ist. Neben der therapeutischen Effizienz ist diese Antikörpertherapie auch durch ein Nebenwirkungsprofil charakterisiert, dem sich die Arbeitsgruppe für chronisch entzündliche Darmerkrankungen innerhalb der ÖGGH in einem umfassenden Konsensuspapier gewidmet hat. Infliximab stellt eine wirksame Therapieoption für oben genannte Indikationen dar; der professionelle Umgang mit dieser Substanz erfordert allerdings das nötige Fachwissen, um das Nutzen-Risiko-Profil für jeden Patienten individuell gut abschätzen zu können.

Abstract

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn’s disease (CD), fistulating Crohn’s disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually.

Schlüsselwörter

Infliximab - chronisch entzündliche Darmerkrankungen - Morbus Crohn - Morbus Crohn mit Fistelbildung - Colitis ulcerosa

Key words

infliximab - inflammatory bowel disease - Crohn’s disease - fistulating Crohn’s disease - ulcerative colitis

Literatur

• 1 Miehsler W, Novacek G, Wenzl H et al. A decade of Infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel diseases.  Journal of Crohn’s and Colitis. (in Druck)
• 2 Reinisch W, Dejaco C, Knoflach P et al. Immunsuppressiva in der Therapie chronisch-entzündlicher Darmerkrankungen.  Z Gastroenterol. 2004;  9 1033-1045
• 3 Ten Hove T, Montfrans van C, Peppelenbosch M P et al. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn’s disease.  Gut. 2002;  50 206-211
• 4 Lugering A, Schmidt A, Lugering N et al. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway.  Gastroenterology. 2001;  121 1145-1157
• 5 Di Sabatino A, Ciccocioppo R, Cinque B et al. Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn’s disease.  Gut. 2004;  53 70-77
• 6 Hyams J, Crandall W, Kugathasan S et al. REACH Study Group. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children.  Gastroenterology. 2007;  132 863-73
• 7 Lemann M, Mary J Y, Duclos B et al. Groupe d’Etude Therapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial.  Gastroenterology. 2006;  130 1054-1061
• 8 Sandborn W J et al. SONIC: A Randomized, Double-Blind, Controlled Trial Comparing Infliximab and Infliximab and Azathioprine to Azathioprine in Pastients with Crohn’s Disease Naïve to Immunomodulators and Biologic Therapy.  Am J Gastroenterol. 2008;  103 1117
• 9 Targan S R, Hanauer S B, Deventer S J et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group.  N Engl J Med. 1997;  337 1029-1035
• 10 Hanauer S B, Feagan B G, Lichtenstein G R et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial.  Lancet. 2002;  359 1541-1549
• 11 Armuzzi van A, De Pascalis B, Roberto I et al. Long-term scheduled therapy with infliximab in inflammatory bowel disease.  Gastroenterology. 2007;  132 (Suppl 1) A183
• 12 Present D H, Rutgeerts P, Targan S et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease.  N Engl J Med. 1999;  340 1398-1405
• 13 Sands B E, Anderson F H, Bernstein C N et al. Infliximab maintenance therapy for fistulizing Crohn’s disease.  N Engl J Med. 2004;  350 876-885
• 14 Klotz U, Teml A, Schwab M. Clinical pharmacokinetics and use of infliximab.  Clin Pharmacokinet. 2007;  46 645-660
• 15 Rutgeerts P, Feagan B G, Lichtenstein G R et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease.  Gastroenterology. 2004;  126 402-413
• 16 Colombel J F, Sandborn W J, Reinisch W et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease.  N Engl J Med. 2010;  362 1383-1395
• 17 Sandborn W J, Rutgeerts P J, Reinisch W et al.  One year data from the Sonic study: a randomized, double-blind trial comparing infliximab and infliximab plus azathioprine to azathioprine in patients with Crohn’s disease naive to immunomodulators and biologic therapy.  Gastroenterol. 2009;  136 A-116
• 18 Van Assche G, Magdelaine-Beuzelin C, D’Haens G et al. Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial.  Gastroenterology. 2008;  134 1861-1868
• 19 D’Haens G, Baert F, Assche van G et al. Belgian Inflammatory Bowel Disease Research Group, North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial.  Lancet. 2008;  371 660-667
• 20 Baert F, Moortgat L, Van Assche G et al. BELGIAN INFLAMMATORY BOWEL DISEASE RESEARCH GROUP, NORTH-HOLLAND GUT CLUB. Mucosal Healing Predicts Sustained Clinical Remission in Patients with Early-Stage.  Crohn’s Disease. 2010;  138 463-468
• 21 Schnitzler F, Fidder H, Ferrante M et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort.  Gut. 2009;  58 492-500
• 22 Rubenstein J H, Chong R Y, Cohen R D. Infliximab decreases resource use among patients with Crohn’s disease.  J Clin Gastroenterol. 2002;  35 151-156
• 23 Lichtenstein G R, Bala M, Han C et al. Infliximab improves quality of life in patients with Crohn’s disease.  Inflamm Bowel Dis. 2002;  8 237-243
• 24 Lichtenstein G R, Yan S, Bala M et al. Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries.  Am J Gastroenterol. 2004;  99 91-94
• 25 Rutgeerts P, Assche van G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease.  Gastroenterology. 2004;  126 1593-1610
• 26 Louis E, Vernier-Massouille G, Grimaud J et al. Infliximab discontinuation in Crohn’s disease patients in stable remission on combined therapy with immunosuppressors: interim analysis of a prospective cohort study.  Gut. 2008;  57 A66
• 27 Regueiro M, Schraut W, Baidoo L et al. Infliximab for prevention of Crohn’s disease (CD) recurrence after ileal resection.  Am J Gastroenterol. 2008;  103 S412
• 28 Pearson D C, May G R, Fick G H et al. Azathioprine and 6-mercaptopurine in Crohn’s disease. A meta-analysis.  Ann Intern Med. 1995;  123 132-142
• 29 Thia K T, Mahadevan U, Feagan B G et al. Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn’s disease: a randomized, double-blind, placebo-controlled pilot study.  Inflamm Bowel Dis. 2009;  15 17-24
• 30 Miehsler W, Reinisch W, Kazemi-Shirazi L et al. Infliximab: lack of efficacy on perforating complications in Crohn’s disease.  Inflamm Bowel Dis. 2004;  10 36-40
• 31 Lichtenstein G R, Yan S, Bala M et al. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease.  Gastroenterology. 2005;  128 862-869
• 32 Lichtenstein G R, Olson A, Bao W et al. Infliximab does not result in an increased risk of intestinal strictures or obstruction in Crohn’s Disease Patients: ACCENT I Study Results.  Am J Gastroenterol. 2002;  97 S254
• 33 Lichtenstein G R, Olson A, Travers S et al. Factors associated with the development of intestinal strictures or obstructions in patients with Crohn’s disease.  Am J Gastroenterol. 2006;  101 1030-1038
• 34 Lichtenstein G R, Stein R, Lewis J D et al. Response to infliximab is decreased in the presence of intestinal strictures in patients with Crohn’s disease.  Am J Gastroenterol. 1999;  94 2691
• 35 Louis E, Boverie J, Baert F et al. Treatment of small bowel inflammatory stricturing Crohn’s disease with infliximab: an open pilot study.  Gastroenterology. 2006;  130 A 215
• 36 Weinberg A, Rattan S, Lewis J et al. Strictures and response to infliximab in Crohn’s disease.  Am J Gastroenterol. 2002;  97 S255
• 37 Prajapati D N, Saeian K, Kim J P et al. Symptomatic luminal stricture underlies infliximab non-response in Crohn’s disease (CD).  Gastroenterology. 2002;  122 A100
• 38 Matsumoto T, Iida M, Motoya S et al. Therapeutic efficacy of infliximab on patients with short duration of Crohn’s disease: A Japanese multicenter survey.  Dis Col Rectum. 2008;  51 916-923
• 39 Holtmann M, Wanitschke R, Helisch A et al. Anti-TNF antibodies in the treatment of inflammatory intestinal stenosis in Crohn’s disease.  Z Gastroenterol. 2003;  41 11-17
• 40 Knapp A B, Mirsky F J, Dillon E H et al. Successful infliximab therapy for a stricture caused by Crohn’s disease.  Inflamm Bowel Dis. 2005;  11 1123-1124
• 41 Pallotta N, Barberani F, Hassan N A et al. Effect of infliximab on small bowel stenosis in patients with Crohn’s disease.  World J Gastroenterol. 2008;  14 1885-1890
• 42 Pelletier A L, Kalisazan B, Wienckiewicz J et al. Infliximab treatment for symptomatic Crohn’s disease strictures.  Aliment Pharmacol Therapeut. 2009;  29 279-285
• 43 Sorrentino. Role of biologics and other therapies in stricturing Crohn’s disease: What have we learnt so far?.  Digestion. 2008;  77 38-47
• 44 Clayton T H, Walker B P, Stables G I. Treatment of chronic erythema nodosum with infliximab.  Clin Exp Dermatol. 2006;  31 823-824
• 45 Regueiro M, Valentine J, Plevy S et al. Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease.  Am J Gastroenterol. 2003;  98 1821-1826
• 46 Brooklyn T N, Dunnill M GS, Shetty A et al. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double-blind, placebo controlled trial.  Gut. 2006;  55 505-509
• 47 Joseph A, Raj D, Dua H S et al. Infliximab in the treatment of refractory posterior uveitis.  Ophthalmology. 2003;  110 1449-1453
• 48 El-Shabrawi Y, Hermann J. Anti-tumor necrosis factor-alpha therapy with infliximab as an alternative to corticosteroids in the treatment of human leukocyte antigen B 27-associated acute anterior uveitis.  Ophthalmology. 2002;  109 2342-2346
• 49 Fries W, Giofre M R, Catanoso M et al. Treatment of aucte uveitis associated with Crohn’s disease and sacroileitis with infliximab.  Am J Gastroenterol. 2002;  97 499-500
• 50 Murphy C C, Ayliffe W H, Booth A et al. Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis.  Ophthalmology. 2004;  111 352-356
• 51 Braun J, Baraliakos X, Listing J et al. Decreased incidenc of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept.  Arthritis Rheum. 2005;  52 2447-2451
• 52 Suhler E B, Smith J R, Wertheim M S et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes.  Arch Ophthalmol. 2005;  123 903-912
• 53 Herfarth H, Obermeier F, Andus T et al. Improvement of arthritis and arthralgia after treatment with infliximab (Infliximab) in a German prospective, open-label, multicenter trial in refractory Crohn’s disease.  Am J Gastroenterol. 2002;  97 2688-2690
• 54 Van den Bosch F, Kruithof E, Baeten D et al. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy.  Arthritis Rheum. 2002;  46 755-765
• 55 Braun J, Brandt J, Listing J et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.  Lancet. 2002;  359 1187-1193
• 56 Gorman J D, Sack K E, Davis Jr J C. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha.  N Engl J Med. 2002;  346 1349-1356
• 57 Van der Heijde D, Dijkmans B, Geusens P et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized placebo-controlled trial (ASSERT).  Arthritis & Rheumatism. 2005;  52 582-591
• 58 Van den Bosch F, Kruithof E, De Vos M et al. Crohn’s disease associated with spondyloarthropathy: effect of TNF-alpha blockade with infliximab on articular symptoms.  Lancet. 2000;  356 1821-1822
• 59 Braun J, Baraliakos X, Listing J et al. Differences in the Incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor agents.  Arthritis & Rheumatism (Arthritis Care & Research). 2007;  57 639-647
• 60 Van der Heijde D, Han C, DeVlam K et al. Infliximab improves productivity and reduces workday loss in patients with ankylosing spondylitis: results from a randomized, placebo-controlled trial.  Arthritis Rheum. 2006;  55 569-574
• 61 Hommes D W, Erkelens W, Ponsioen C et al. A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis.  J Clin Gastroenterol. 2008;  42 522-526
• 62 Abreu M T, Geller J L, Vasiliauskas E A et al. Treatment with infliximab is associated with increased markers of bone formation in patients with Crohn’s disease.  J Clin Gastroenterol. 2006;  40 55-63
• 63 Bernstein M, Irwin S, Greenberg G R. Maintenance infliximab treatment is associated with improved bone mineral density in Crohn’s disease.  Am J Gastroenterol. 2005;  100 2031-2035
• 64 Lichtenstein G R, Cohen R D, Feagan B G et al. Safety Of Infliximab and Others Crohn’s Disease Therapies – Updated TREATTM Registry DATA With nearly 20,000 Patient-Years Of Follow-Up.  Gastroenterology. 2007;  132 A178
• 65 Tay G S, Binion D G, Eastwood D et al. Multivariate analysis suggests improved perioperative outcome in Crohn’s disease patients receiving immunomodulator therapy after segmental resection and/or strictureplasty.  Surgery. 2003;  134 565-572
• 66 Colombel J F, Loftus E V, Tremaine W J et al. The safety profile of infliximab in patients with Crohn’s disease: The Mayo clinic experience in 500 patients.  Gastroenterology. 2004;  126 19-31
• 67 Marchal L, D’Haens G, Van Assche G et al. The risk of post-operative complications associated with infliximab therapy for Crohn’s disease: a controlled cohort study.  Aliment Pharmacol Ther. 2004;  19 749-754
• 68 Appau K A, Fazio V W, 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 1738-1734
• 69 Kunitake H, Hodin R, Shellito P C et al. Perioperative treatment with infliximab in patients with Crohn’s disease and ulcerative colitis is not associated with an increased rate of postoperative complications.  J Gastrointest Surg. 2008;  12 1730-1736
• 70 Katz J A, Antoni C, Keenan G F et al. Outcome of pregnancy in women receiving infliximab for the treatment of Crohn’s disease and rheumatoid arthritis.  Am J Gastroenterol. 2004;  99 2385-2392
• 71 Mahadevan U, Kane S, Sandborn W J et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn’s disease.  Aliment Pharmacol Ther. 2005;  21 733-738
• 72 Carter J D, Ladhani A, Ricca L R et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database.  J Rheumatol. 2009;  36 635-641
• 73 Vasiliauskas E A, Church J A, Silverman N et al. Case report: Evidence for transplacental transfer of maternally administered infliximab to the newborn.  Clin Gastroenterol Hepatol. 2006;  4 1255-1258
• 74 Rutgeerts P, Van Assche G, Vermeire S. Review article: Infliximab therapy for inflammatory bowel disease – seven years on.  Aliment Pharmacol Ther. 2006;  23 451-463
• 75 O’Donnell S, O’Morain C. Review article: use of antitumour necrosis factor therapy in inflammatory bowel disease during pregnancy and conception.  Aliment Pharmacol Ther. 2008;  27 885-894