Zweiter österreichischer Konsensus zur sicheren Anwendung von anti-TNF-α-Antikörpern bei chronisch-entzündlichen Darmerkrankungen

Zusammenfasung

Anti-TNF-α-Antikörper haben die Therapie chronisch-entzündlicher Darmerkrankungen und anderer immunmediierter inflammatorischer Erkrankungen revolutioniert. Der zunehmende Einsatz dieser Substanzen war Anlass, den Konsensusbericht zur sicheren Anwendung von Infliximab der Arbeitsgruppe für Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie aus dem Jahr 2010 zu aktualisieren und auf alle anti-TNF-α-Antikörper zu erweitern. Der vorliegende Konsensusbericht fasst die aktuelle Datenlage zur sicheren Anwendung von anti-TNF-α-Antikörpern zusammen und berücksichtigt folgende Themen: allgemeines Infektionsrisiko, bakterielle Infekte (inkl. Clostridium difficile, Tuberkulose, Nahrungsmittelhygiene), Pneumozystis jiroveci, virale Infektionen (inkl. Hepatitis B, Hepatitis C, HIV, CMV, VZV), Impfungen und Impfempfehlungen, gastrointestinale Aspekte (perianale Fistel, abdominale Fistel, Stenose), dermatologische Aspekte (Haut-Malignome, Ekzem-ähnliche anti-TNF-α-assoziierte Hautläsionen), Infusionsreaktionen und Immunogenität, demyelinisierende Erkrankungen, Hepatotoxizität, Hämatotoxizität, Herzinsuffizienz, Malignomrisiko und Einsatz nach Malignomen, sowie Schwangerschaft und Stillen. Da der Konsensusbericht als praktischer Leitfaden für die sichere Anwendung dieser Substanzen dienen soll, wurden die relevanten Aspekte in einer Checkliste zusammengefasst, die sich in zwei Teile „vor Therapie“ und „während Therapie“ gliedert.

Abstract

Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i. e., Clostridium difficile, Tuberculosis, food hygiene), Pneumocystis jiroveci, viral infections (i. e., Hepatitis B, Hepatitis C, HIV, CMV, VZV), vaccination in general and recommendation for vaccines, gastrointestinal aspects (i. e., perianal fistula, abdominal fistula, intestinal strictures, stenosis and bowel obstruction), dermatologic aspects (skin malignancies, eczema-like drug-related skin eruption), infusion reactions and immunogenicity, demyelinating diseases, hepatotoxicity, haematotoxicity, congestive heart failure, risk and history of malignancies, and pregnancy and breast feeding. For practical reasons, the relevant aspects are summarized in a checklist which is divided into two parts: issues to be addressed before therapy and issues to be addressed during therapy.

Schlüsselwörter

chronisch entzündliche Darmerkrankung - Infliximab - Adalimumab - Golimumab - anti-TNFα - Infektion - Sicherheit - Malignom - Impfung - Schwangerschaft - Colitis ulcerosa - Morbus Crohn

Key words

inflammatory bowel disease - Infliximab - Adalimumab - Golimumab - anti-TNFα - infection - safety - malignancy - vaccine - pregnancy - ulcerative colitis - Crohn's disease

• 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 disease. J Crohns Colitis 2010; 4: 221-256
• 2 Rahier JF, Magro F, Abreu C. et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2014; 8: 443-468
• 3 Lichtenstein GR, Feagan BG, Cohen RD. et al. Serious Infection and Mortality in Patients With Crohn’ s Disease: More Than 5 Years of Follow-Up in the TREAT™ Registry. Am J Gastroenterol 2012; 107: 1409-1422
• 4 Burmester GR, Panaccione R, Gordon KB. et al. Adalimumab: a long term safety in 23458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 2013; 72: 517-524
• 5 Bonovas S, Fiorino G, Allocca M. et al. Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol 2016; 14: 1385-1397
• 6 Colombel JF, Sandborn WJ, Reinisch W. et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 362: 1383-1395
• 7 Feagan BG, McDonald JW, Panaccione R. et al. Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn’s disease. Gastroenterology 2014; 146: 681-688
• 8 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
• 9 Jones J, Kaplan G, Peyrin-Biroulet L. et al. Impact of concomitant immunomodulator treatment on efficacy and safety of anti-TNF therapy in Crohn’s disease: a meta-analysis of placebo controlled trials with individual patient-level data. Gastroenterology 2013; 144 (Suppl. 01) S179
• 10 Lichtenstein G, Diamond R, Wagner C. 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: 210-226
• 11 Schneeweiss S, Korzenik J, Solomon D. et al. Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther 2009; 30: 253-264
• 12 Fidder H, Schnitzler F, Ferrante M. et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut 2009; 58: 501-508
• 13 Toruner M, Loftus EV Jr, Harmsen WS. et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 929-936
• 14 D’Haens G, Reinisch W, Satsangi J. et al. Long-term safety of adalimumab in patients with Crohn’s disease: final data from PYRAMID registry. J Crohn Colitis 2017; 11 (Suppl. 01) P353
• 15 Naganuma M, Kunisaki R, Yoshimura N. et al. A prospective analysis of the incidence of and risk factors for opportunistic infections in patients with inflammatory bowel disease. J Gastroenterol 2013; 48: 595-600
• 16 Curtis S, Yang N, Patkar E. et al. Risk of Hospitalized Bacterial Infections Associated With Biologic Treatment Among US Veterans With Rheumatoid Arthritis. Arthritis Care & Research 2014; 66: 990-997
• 17 Lanternier F, Tubach F, Ravaud P. et al. Incidence and risk factors of Legionella pneumophila pneumonia during anti-tumor necrosis factor therapy: a prospective French study. Chest 2013; 144: 990-998
• 18 Rahier JF, Ben-Horin S, Chowers Y. et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. Journal of Crohn's and Colitis 2009; 3: 47-91
• 19 Keane J, Gershon S, Wise R. et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345: 1098-1104
• 20 Byun J, Lee C, Rhee S. et al. Risks for opportunistic tuberculosis infection in a cohort of 873 patients with inflammatory bowel disease receiving a tumor necrosis factor-α-inhibitor. Scand J Gastroenterol 2015; 50: 312-320
• 21 Lorenzetti R, Zullo A, Ridola L. et al. Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive agents: a systematic review of randomized controlled trials. Ann Med 2014; 46: 547-554
• 22 Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V. et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 2005; 52: 1766-1772
• 23 Takeuchi T, Tatsuki Y, Nogami Y. et al. Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis 2008; 67: 189-194
• 24 Leeb B, Thalhammer F. et al. Tuberkulose & Biologika – Consensus Statement. Österreichische Ärztezeitung 2011; (Supplementum): 1-12
• 25 Diel R, Hauer B, Loddenkemper R. et al. Recommendations for tuberculosis screening before initiation of TNF-alpha-inhibitor treatment in rheumatic diseases. Pneumologie 2009; 63: 329-334
• 26 Diel R, Goletti D, Ferrara G. et al. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J 2011; 37: 88-99
• 27 Shahidi N, Fu Y-TN, Qian H. et al. Performance of interferon-gamma release assays in patients with inflammatory bowel disease: A systematic review and meta-analysis. Inflamm Bowel Dis 2012; 18: 2034-2042
• 28 Wong SH, Ip M, Tang W. et al. Performance of interferon-gamma release assay for tuberculosis screening in inflammatory bowel disease patients. Inflamm Bowel Dis 2014; 20: 2067-2072
• 29 Papay P, Eser A, Winkler S. et al. Factors impacting the results of interferon-γ release assay and tuberculin skin test in routine screening for latent tuberculosis in patients with inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17: 84-90
• 30 Yang J, Jo K, Hong S. et al. Adequacy of initiating TNF antagonists within 3 weeks of starting latent tuberculosis infection treatment in patients with immune-mediated inflammatory diseases. Infect Dis 2015; 14: 1-6
• 31 Ormerod L, Milburn H, Gillespie S. et al. British Thoracic Soc Stand Care. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment. Thorax 2005; 60: 800-805
• 32 Theis V, Rhodes J. Review article: minimizing tuberculosis during anti-tumor necrosis factor-alpha treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2008; 27: 19-30
• 33 Debeuckelaere C, De Munter P, Van Bleyenbergh P. et al. Tuberculosis infection following anti-TNF therapy in inflammatory bowel disease, despite negative screening. J Crohns Colitis 2014; 8: 550-557
• 34 Cantini F, Lubrano E, Marchesoni A. et al. Latent tuberculosis infection detection and active tuberculosis prevention in patients receiving anti-TNF therapy: an Italian nationwide survey. Int J Rheum Dis 2016; 19: 799-805
• 35 Trifan A, Stanciu C, Stoica O. et al. Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review. World J Gastroenterol 2014; 20: 11736-11742
• 36 Negron M, Rezaie A, Barkema H. et al. Ulcerative Colitis Patients With Clostridium difficile are at Increased Risk of Death, Colectomy, and Postoperative Complications: A Population-Based Inception Cohort Study. Am J Gastroenterol 2016; 111: 691-704
• 37 Ben-Horin S, Margalit M, Bossuyt P. et al. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection. Clin Gastroenterol Hepatol 2009; 7: 981-987
• 38 Horton HA, Dezfoli S, Berel D. et al. Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease. Antimicrob Agents Chemother 2014; 58: 5054-5059
• 39 Rumman A, Bahreini Z, McGeer A. et al. Recurrence of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease: The RECIDIVISM Study. Am J Gastroenterol 2016; 111: 1141-1146
• 40 Abreu C, Magro F, Vilas-Boas F. et al. Listeria infection in patients on anti-TNF treatment: report of two cases and review of the literature. J Crohns Colitis 2013; 7: 175-182
• 41 Kesteman T, Yombi J, Gigi J. et al. Listeria infections associated with infliximab: case reports. Clin Rehumatol 2007; 26: 2173-2175
• 42 Kuehn B. Growing List of Infections Linked to TNF Blockers. JAMA 2011; 306: 1430
• 43 Dederichs F, Pinciu F, Gerhard H. et al. Listerienmeningitis bei einem Patienten mit Morbus Crohn – eine seltene, aber klinisch-relevante Nebenwirkung der Therapie mit Infliximab. Z Gastroenterol 2006; 44: 657-660
• 44 Slifman N, Gershon S, Lee J. et al. Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor α-neutralizing agents. Arthritis Rheum 2003; 48: 319-324
• 45 Glück T, Linde HJ, Scholmerich J. et al. Anti-tumor necrosis factor therapy and Listeria monocytogenes infection: report of two cases. Arthritis Rheum 2002; 46: 2255-2257
• 46 Peña-Sagredo J, Hernández M, Fernandez-Llanio N. et al. Listeria monocytogenes infection in patients with rheumatic diseases on TNF-alpha antagonist therapy: the Spanish Study Group experience. Clin Exp Rheumatol 2008; 26: 854-859
• 47 Davies R, Dixon W, Watson K. et al. Influence of anti-TNF patient warning regarding avoidance of high risk foods on rates of listeria and salmonella infections in the UK. Ann Rheum Dis 2013; 72: 461-462
• 48 Nordgaard-Lassen I, Dahlerup J, Belard E. et al. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment. Dan Med J 2012; 59: C4480
• 49 Connell W, Andrews JM, Brown S. et al. Practical guidelines for treating inflammatory bowel disease safely with anti-tumour necrosis factor therapy in Australia. Intern Med J 2010; 40: 139-149
• 50 Seddik M, Meliez H, Seguy D. et al. Pneumocystis jiroveci (carinii) pneumonia following initiation of infliximab and azathioprine therapy in a patient with Crohn’s disease. Inflamm Bowel Dis 2004; 10: 436-743
• 51 Velayos F, Sandborn W. Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004; 10: 657-660
• 52 Kaur N, Mahl T. Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases. Dig Dis Sci 2007; 52: 1481-1484
• 53 Estrada S, García-Campos F, Calderón R. et al. Pneumocystis jiroveci (carinii) pneumonia following a second infusion of infliximab in a patient with ulcerative colitis. Inflamm Bowel Dis 2009; 15: 315-316
• 54 Komano Y, Harigai M, Koike R. et al. Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case-control study of 21 patients. Arthritis Rheum 2009; 61: 305-312
• 55 Kameda H, Tokuda H, Sakai F. et al. Clinical and radiological features of acute-onset diffuse interstitial lung diseases in patients with rheumatoid arthritis receiving treatment with biological agents: importance of Pneumocystis pneumonia in Japan revealed by a multicenter study. Intern Med 2011; 50: 305-313
• 56 Stern A, Green H, Paul M. et al. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev 2014; 10: CD005590
• 57 Bodro M, Paterson D. Has the time come for routine trimethoprim-sulfamethoxazole prophylaxis in patients taking biologic therapies?. Clin Infect Dis 2013; 56: 1621-1628
• 58 Tanaka M, Sakai R, Koike R. et al. Pneumocystis jirovecii pneumonia in Japanese patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: A Pooled Analysis of 3 Agents. J Rheumatol 2015; 42: 1726-1728
• 59 Bourne E, Dimou J. Invasive central nervous system aspergillosis in a patient with Crohn’s disease after treatment with infliximab and corticosteroids. J Clin Neurosci 2016; 30: 163-164
• 60 Kobak S, Yılmaz H, Güclü O. et al. Severe candida laryngitis in a patient with rheumatoid arthritis treated with adalimumab. Eur J Rheumatol 2014; 1: 167-169
• 61 Alonso-Serra M, Calvo M, Gonzalez-Lama Y. Nocardia and Aspergillus Coinfection in a Patient with Ulcerative Colitis during Golimumab Therapy. J Crohns Colitis 2016; 10: 1127-1128
• 62 Singh S, Rau N, Cohen L. et al. Cutaneous nocardiosis complicating management of Crohn’s disease with infliximab and prednisone. Can Med Assoc J 2004; 171: 1063-1064
• 63 Warris A, Bjorneklett A, Gaustad P. Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med 2001; 344: 1099-1100
• 64 De Rosa F, Shaz D, Campagna A. et al. Invasive pulmonary aspergillosis soon after therapy with infliximab, a tumor necrosis factor-alpha- neutralizing antibody: a possible healthcare-associated case?. Infect Control Hosp Epidemiol 2003; 24: 477-482
• 65 Belda A, Hinojosa J, Serra B. et al. Systemic candidiasis and infliximab therapy. Gastroenterol Hepatol 2004; 27: 365-367
• 66 Bergstrom L, Yocum D, Ampel N. et al. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists. Arthritis Rheum 2004; 50: 1959-1966
• 67 Shrestha R, Stoller J, Honari G. et al. Pneumonia due to Cryptococcus neoformans in a patient receiving infliximab: possible zoonotic transmission from a pet cockatiel. Respir Care 2004; 49: 606-608
• 68 Vergidis P, Avery R, Wheat L. et al. Histoplasmosis complicating tumor necrosis factor-α-blocker therapy: a retrospective analysis of 98 cases. Clin Infect Dis 2015; 61: 409-417
• 69 Abreu C, Rocha-Pereira N, Sarmento A. et al. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review. World J Gastroenterol 2015; 21: 6491-6498
• 70 Papa A, Felice C, Marzo M. et al. Prevalence and natural history of hepatitis B and C infections in a large population of IBD patients treated with anti-tumor necrosis factor-α-agents. J Crohns Colitis 2013; 7: 113-119
• 71 Katsanos K, Tsianos V, Zois C. et al. Northwest Greece IBD Study Group. Inflammatory bowel disease and hepatitis B and C in Western Balkans: a referral centre study and review of the literature. J Crohns Colitis 2010; 4: 450-465
• 72 Loras C, Saro C, Gonzalez-Huix F. et al. Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study. Am J Gastroenterol 2009; 104: 57-63
• 73 Chevaux J, Nani A, Oussalah A. et al. Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France. Inflamm Bowel Dis 2010; 16: 916-924
• 74 Brunasso A, Puntoni M, Gulia A. et al. Safety of anti-tumour necrosis factor agents in patients with chronic hepatitis C infection: a systematic review. Rheumatology 2011; 50: 1700-1711
• 75 Abdelmalek M, Liu C, Valentine J. Successful treatment of chronic hepatitis C with pegylated interferon, ribavirin, and infliximab in a patient with Crohn’s disease. Am J Gastroenterol 2007; 102: 1333-1334
• 76 Campbell S, Ghosh S. Infliximab therapy for Crohn’s disease in the presence of chronic hepatitis C infection. Eur J Gastroenterol Hepatol 2001; 13: 191-192
• 77 Holtmann M, Galle P, Neurath M. Treatment of patients with Crohn’s disease and concomitant chronic hepatitis C with a chimeric monoclonal antibody to TNF. Am J Gastroenterol 2003; 98: 504-505
• 78 Biancone L, Del VecchioBlanco G, Pallone F. et al. Immunomodulatory drugs in Crohn’s disease patients with hepatitis B or C virus infection. Gastroenterology 2002; 122: 593-594
• 79 Alderson J, Van Dinter TG Jr, Opatowsky M. et al. Disseminated aspergillosis following infliximab therapy in an immunosuppressed patient with Crohn’s disease and chronic hepatitis C: a case study and review of the literature. Med Gen Med 2005; 7: 7
• 80 Haennig A, Bonnet D, Thebault S. et al. Infliximab-induced acute hepatitis during Crohn’s disease therapy: absence of cross-toxicity with adalimumab. Gastroenterol Clin Biol 2010; 34: e7-e8
• 81 Lin M, Blonski W, Buchner A. et al. The influence of anti-TNF therapy on the course of chronic hepatitis C virus infection in patients with inflammatory bowel disease. Dig Dis Sci 2013; 58: 1149-1156
• 82 Loras C, Gisbert J, Saro M. et al. Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: Multicenter prospective observational study (REPENTINA 3). Journal of Crohn’s and Colitis 2014; 8: 1529-1538
• 83 Zein N. Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study. J Hepatol 2005; 42: 315-322
• 84 Scherzer T, Staufer K, Novacek G. et al. Efficacy and safety of antiviral therapy in patients with Crohn’s disease and chronic hepatitis C. Aliment Pharmacol Ther 2008; 28: 742-748
• 85 Allen A, Kim W, Larson J. et al. Efficacy and safety of treatment of hepatitis C in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11: 1655-1660
• 86 Hahn K, Kohli A, Sims Z. et al. Durable Sustained Virologic Response After Oral Directly Acting Antiviral Therapy Despite Immunosuppressive Treatment. Open Forum Infect Dis 2015; 2: ofv091
• 87 Esteve M, Saro C, Gonzales-Huix F. et al. Chronic hepatitis B reactivation following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut 2004; 53: 1363-1365
• 88 Millonig G, Kern M, Ludwiczek O. et al. Subfulminant hepatitis B after infliximab in Crohn’s disease: need for HBV-screening?. World J Gastroenterol 2006; 12: 974-976
• 89 Esteve M, Loras C, Gonzales-Huix F. et al. Lamivudine resistance and exacerbation of hepatitis B in infliximab-treated Crohn’s disease patient. Inflamm Bowel Dis 2007; 13: 1450-1451
• 90 Colbert C, Chavarria A, Berkelhammer C. Fulminant hepatic failure in chronic hepatitis B on withdrawal of corticosteroids, azathioprine and infliximab for Crohn’s disease. Inflamm Bowel Dis 2007; 13: 1453-1454
• 91 Madonia S, Orlando A, Scimeca D. et al. Occult hepatitis B and infliximab-induced reactivation. Inflamm Bowel Dis 2007; 13: 508-509
• 92 Gisbert J, Villagrasa J, Rodríguez-Nogueiras A. et al. Efficacy of hepatitis B vaccination and revaccination and factors impacting on response in patients with inflammatory bowel disease. Am J Gastroenterol 2012; 107: 1460-1466
• 93 Gisbert J, Menchén L, García-Sánchez V. et al. Comparison of the effectiveness of two protocols for vaccination (standard and double dosage) against hepatitis B virus in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2012; 35: 1379-1385
• 94 Gisbert J, Villagrasa J, Rodríguez-Nogueiras A. et al. Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 554-558
• 95 EASL. clinical practice guidelines: Management of chronic hepatitis B  virus infection. J Hepatol 2012; 57: 167-185
• 96 Aboulafia D, Bundow D, Wilske K. et al. Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis. Mayo Clin Proc 2000; 75: 1093-1098
• 97 Duh E, Maury W, Folks T. et al. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci USA 1989; 86: 5974-5978
• 98 Valdez H, Lederman M. Cytokines and cytokine therapies in HIV infection. AIDS Clin Rev 1997–1998: 187-228
• 99 Ho T, Cohen B, Colombel J. et al. Review article: the intersection of mucosal pathophysiology in HIV and inflammatory bowel disease, and its implications for therapy. Aliment Pharmacol Ther 2014; 40: 1171-1186
• 100 Galeazzi M, Giannitti C, Manganelli S. et al. Treatment of rheumatic diseases in patients with HCV and HIV infection. Autoimmun Rev 2008; 8: 100-103
• 101 Beltrán B, Nos P, Bastida G. et al. Safe and effective application of anti-TNF-alpha in a patient infected with HIV and concomitant Crohn’s disease. Gut 2006; 55: 1670-1671
• 102 Habib S, Hasan M, Salam I. Infliximab therapy for HIV positive Crohn’s disease: A case report. J Crohn Colitis 2009; 3: 302-304
• 103 Cepeda E, Williams F, Ishimori M. et al. The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis 2008; 67: 710-712
• 104 Viazis N, Vlachogiannakos J, Georgiou O. et al. Course of inflammatory bowel disease in patients infected with human immunodeficiency virus. Inflamm Bowel Dis 2010; 16: 507-511
• 105 Filippi J, Roger P, Schneider S. et al. Infliximab and human immunodeficiency virus infection: Viral load reduction and CD4+ T-cell loss related to apoptosis. Arch Intern Med 2006; 166: 1783-1784
• 106 Wallis R, Kyambadde P, Johnson J. et al. A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 2004; 18: 257-264
• 107 Matsuoka K, Iwao Y, Mori T. et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol 2007; 102: 331-337
• 108 Papadakis K, Tung J, Binder S. et al. Outcome of cytomegalovirus infections in patients with inflammatory bowel disease. Am J Gastroenterol 2001; 96: 2137-2142
• 109 Roblin X, Pillet S, Oussalah A. et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol 2011; 106: 2001-2008
• 110 McCurdy J, Enders F, Jones A. et al. Detection of Cytomegalovirus in patients with inflammatory bowel disease: where to biopsy and how many biopsies?. Inflamm Bowel Dis 2015; 21: 2833-2838
• 111 Delvincourt M, Lopez A, Pillet S. et al. The impact of cytomegalovirus reactivation and its treatment on the course of inflammatory bowel disease. Aliment Pharmacol Ther 2014; 39: 712-720
• 112 McCurdy J, Jones A, Enders F. et al. A model for identifying cytomegalovirus in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2015; 13: 131-137
• 113 Hirayama Y, Ando T, Hirooka Y. et al. Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis. World J Gastrointest Endosc 2016; 8: 301-309
• 114 Schepers K, Hernandez A, Andrei G. et al. Acyclovir-resistant herpes simplex encephalitis in a patient treated with anti-tumor necrosis factor-α-monoclonal antibodies. J Clin Virol 2014; 59: 67-70
• 115 Baumgart DC, Grittner U, Steingräber A. et al. Frequency, phenotype, outcome, and therapeutic impact of skin reactions following initiation of adalimumab therapy: experience from a consecutive cohort of inflammatory bowel disease patients. Inflamm Bowel Dis 2011; 17: 2512-2520
• 116 Salmon-Ceron D, Tubach F, Lortholary O. et al. Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry. Ann Rheum Dis 2011; 70: 616-623
• 117 Shale M, Seow C, Coffin C. et al. Review article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease. Aliment Pharmacol Ther 2010; 31: 20-34
• 118 Jansen L, Vos X, Löwenberg M. Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis. World J Clin Cases 2016; 4: 60-62
• 119 Haag L, Hofmann J, Kredel L. et al. Herpes simplex virus sepsis in a young woman with Crohn’s disease. J Crohns Colitis 2015; 9: 1169-1173
• 120 Colombel JF, Loftus E, Tremaine W. et al. The safety profile of Inbfliximab in patients with Crohn’s disease: the Mayo Clinic expereince in 500 patients. Gastroenterology 2004; 126: 19-31
• 121 Tougeron D, Mauillon J, Tranvouez J. Severe varicella infection during treatment with infliximab for Crohn’s disease. Gastroenterol Clin Biol 2006; 30: 1410-1413
• 122 Vonkeman H, ten NapelC, Rasker H. et al. Disseminated primary varicella infection during infliximab treatment. J Rheumatol 2004; 31: 2517-2518
• 123 Leung V, Nguyen M, Bush T. Disseminated primary varicella after initiation of infliximab for Crohn’s disease. Am J Gastroenterol 2004; 99: 2503-2504
• 124 Lawrance I, Radford-Smith G, Bampton P. et al. Serious infections in patients with inflammatory bowel disease receiving anti-tumor-necrosis-factor-alpha therapy: an Australian and New Zealand experience. J Gastroenterol Hepatol 2010; 25: 1732-1738
• 125 Elwir S, Shaffer C, Arvan S. et al. Disseminated varicella zoster virus infection with encephalitis in a UC patient receiving Infliximab. Gastroenterol Hepatol 2013; 9: 54-56
• 126 Ricart E, Panaccione R, Loftus E. et al. Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: the first 100 patients. Am J Gastroenterol 2001; 96: 722-729
• 127 Shale M. The implications of anti-tumour necrosis factor therapy for viral infection in patients with inflammatory bowel disease. Br Med Bull 2009; 92: 61-77
• 128 Di Costanzo L, Ayala F, Megna M. et al. The risk of herpes zoster in the anti-TNF-α-era: a case report and review of the literature. J Dermatol Case Rep 2013; 7: 1-4
• 129 Bakker N, van Imhoff G, Verschuuren E. et al. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transpl Int 2007; 20: 207-218
• 130 Wong N, Herbst H, Herrmann K. et al. Epstein-Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas. J Pathol 2003; 201: 312-318
• 131 Schwartz L, Kim M, Coleman M. et al. Case report: lymphoma araising in an ileal pouch anal anastomosis after immunomodulatory therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol 2006; 4: 1030-1034
• 132 Losco A, Gianelli U, Cassani B. et al. Epstein-Barr virus-associated lymphoma in Crohn’s disease. Inflamm Bowel Dis 2004; 10: 425-429
• 133 Bai M, Katsano K, Economou M. et al. Rectal Epstein-Barr virus-positive Hodgkin’s lymphoma in a patient with Crohn’s disease: case report and review of the literature. Scand J Gastroenterol 2006; 41: 866-869
• 134 Cezard J, Nouaili N, Talbotec C. et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factor (remicade) in severe pediatric Crohn’s disease. J Pediatr Gastroenterol Nutr 2004; 39: 302-303
• 135 Reijasse D, Le PendevenC, Cosnes J. et al. A Epstein-Barr virus viral load in Crohn’s disease: effect of immunosuppressive therapy. Inflamm Bowel Dis 2004; 10: 85-90
• 136 Lavagna A, Bergallo M, Daperno M. et al. Infliximab and the risk of latent viruses reactivation in active Crohn’s disease. Iflamm Bowel Dis 2007; 13: 896-902
• 137 Magro F, Santos-Antunes J, Albuquerque A. et al. Epstein-Barr virus in inflammatory bowel disease – correlation with different therapeutic regimens. Inflamm Bowel Dis 2013; 19: 1710-1716
• 138 Beaugerie L, Brousse N, Bouvier A. et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374: 1617-1625
• 139 Vos A, Bakkal N, Minnee R. et al. Risk of malignant lymphoma in patients with inflammatory bowel disease: a Dutch nationwide study. Inflamm Bowel Dis 2011; 17: 1837-1845
• 140 Linton M, Kroeker K, Fedorak D. et al. Prevalence of Epstein-Barr Virus in a population of patients with inflammatory bowel disease: a prospective cohort study. Aliment Pharmacol Ther 2013; 38: 1248-1254
• 141 Funch D, Walker A, Schneider G. et al. Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients. 2005 Dec 5 (12) 2894-2900
• 142 Nissen L, Nagtegaal I, de Jong D. et al. Epstein-Barr Virus in Inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders. J Crohn Colitis 2015; 9: 398-403
• 143 Khan N, Abbas A, Lichtenstein G. et al. Risk of Lymphoma in Patients With Ulcerative Colitis Treated With Thiopurines: A Nationwide Retrospective Cohort Study. Gastroenterology 2013; 145: 1007-1015
• 144 Dayharsh G, Loftus E, Sandborn W. et al. Inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology 2002; 122: 72-77
• 145 Daffra P, Aldecoa I, Ordas I. et al. P086 The presence of the Epstein-Barr virus is associated to a higher colectomy requirement in patients with Ulcerative Colitis. J Crohn Colitis 2015; 9 (Suppl. 01) S121
• 146 Ryan J, Shen YJ, Morgan D. et al. Epstein-Barr virus infection is common in inflamed gastrointestinal mucosa. Dig Dis Sci 2012; 57: 1887-1898
• 147 Elkayam O, Caspi D, Reitblatt T. et al. The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin Arthritis Rheum 2004; 33: 283-288
• 148 Kapetanovic M, Saxne T, Nilsson JA. et al. Influenca vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients. Rheuamtology 2007; 46: 608-611
• 149 Fomin I, Caspi D, Levy V. et al. Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, includine TNF(blockers. Ann Rheum Dis 2006; 65: 191-194
• 150 Kaine J, Kivitz A, Birbara C. et al. Immune response following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol 2007; 34: 272-279
• 151 Gelinck L, van der Bijl A, Beyer W. et al. The effect of anti-tumor necrosis factor (treatment on the antibody response to influenza vaccination. Ann Rheum Dis 2008; 67: 713-716
• 152 Fiorino G, Peyrin-Biroulet L, Naccarato P. et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis 2012; 18: 1042-1047
• 153 Lee C, Kim H, Ye B. et al. Patients with Crohn’s disease on anti-tumor necrosis factor therapy are at significant risk of inadequate response to the 23-valent pneumococcal polysaccharide vaccine. J Crohn Colitis 2014; 8: 384-391
• 154 Visvanathan S, Keenan G, Baker D. et al. Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate or methotrexate alone. J Rheumatol 2007; 34: 952-957
• 155 Kapetanovic M, Saxne T, Sjöholm A. et al. Influence of methotrexate, TNF blockers and prednisolone on antibody response to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology 2006; 45: 106-111
• 156 Andrisani G, Frasca D, Romero M. et al. Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-α-agents: effects of combined therapy with immunosuppressants. J Crohns Colitis 2013; 7: 301-307
• 157 Hagihara Y, Ohfuji S, Watanabe K. et al. Infliximab and/or immunomodulators inhibit immune responses to trivalent influenza vaccination in adults with inflammatory bowel disease. J Crohns Colitis 2014; 8: 223-233
• 158 deBruyn J, Fonseca K, Ghosh S. et al. Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial. Inflamm Bowel Dis 2016; 22: 638-647
• 159 Andrade P, Santos-Antunes J, Rodrigues S. et al. Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients. J Gastroenterol Hepatol 2015; 30: 1591-1595
• 160 Chaparro M, Gordillo J, Domnech E. et al. Durability of the anti-HBs titers after vaccination against Hepatitis B virus (HBV) in patients with Inflammatory Bowel Disease. J Crohn Colitis 2015; 9 (Suppl. 01) 272(P386)
• 161 Huzly D, Neifer S, Reinke P. et al. Routine immunization in adult renal transplant recipients. Transplantation 1997; 63: 839-845
• 162 Pirofski L, Casadevall A. Use of licensed vaccines for active immunization of the immunocompromized host. Clin Microbiol Rev 1998; 11: 1-26
• 163 Borte S, Liebert U, Borte M. et al. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept. Rheumatology 2009; 48: 144-148
• 164 Kano H, Mazuta K, Sakakihara Y. et al. Efficacy and safety of immunization for pre- and post- liver transplant children. Transplantation 2002; 74: 543-550
• 165 Rand E, McCarthy C, Whitington P. Measles vaccination after orthoptic liver transplantation. J Pediatrics 1993; 123: 87-89
• 166 Machado C, de Souza V, Sumita L. et al. Early measles vaccination in bone marrow transplant recipients. Bone Marrow Transplant 2005; 35: 787-791
• 167 Kawano Y, Suzuki M, Kawada J. et al. Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients. Vaccine 2015; 33: 1440-1445
• 168 Azevedo L, Lasmar E, Contieri F. et al. Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study. Transpl Infect Dis 2012; 14: 237-241
• 169 Scheinberg M, Guedes-Barbosa L, Mangueira C. et al. Yellow fever revaccination during infliximab therapy. Arthritis Care Res 2010; 62: 896-898
• 170 Zamora I, Simon J, Da Silva M. et al. Attenuated varicella virus vaccine in children with renal transaplants. Pediatr Nephrol 1994; 8: 190-192
• 171 van de Wetering D, Vossen T, Jansen H. et al. Varicella vaccination in pediatric oncology patients without interruption of chemotherapy. J Clin Virol 2016; 75: 47-52
• 172 Costa E, Buxton J, Brown J. et al. Fatal disseminated varicella zoster infection following zoster vaccination in an immunocompromised patient. BMJ Case Rep 2016;
• 173 Österreichischer Impfplan 2015, Österr Ärzte Z 2015. 4a. 1-32
• 174 Clifford G, Gallus S, Herrero R. et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 2005; 366: 991-998
• 175 Petry K, Köchel H, Bode U. et al. Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women. Gynecol Oncol 1996; 60: 30-34
• 176 Simonsen L, Taylor R, Viboud C. et al. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Inf Dis 2007; 7: 658-666
• 177 Fiore A, Shay D, Haber P. et al. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recom Rep 2007; 56: 1-54
• 178 Targonski P, Poland G. Pneumococcal vaccination in adults: recommendations, trends, and prospects. Cleve J Med 2007; 74: 401-406
• 179 Present D, 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
• 180 Sands B, Anderson F, Bernstein C. et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350: 876-885
• 181 Sands B, Blank M, Diamond R. et al. Maintenance infliximab does not result in increased abscess development in fistulising Crohn’s disease: results from the ACCENT II study. Aliment Pharmacol Ther 2006; 23: 1127-1136
• 182 Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as adjunct under anestesia with seton placement. Inflamm Bowel Dis 2003; 9: 98-103
• 183 Spradlin N, Wise P, Herline A. et al. A randomized prospective trial of endoscopic ultrasound to guide combination medical and surgical treatment for Crohn’s perianal fistulas. Am J Gastroenterol 2008; 103: 2527-2535
• 184 Wiese D, Beaulieu D, Slaughter J. et al. Use of Endoscopic Ultrasound to Guide Adalimumab Treatment in Perianal Crohn’s Disease Results in Faster Fistula Healing. Inflamm Bowel Dis 2015; 21: 1594-1599
• 185 Ng S, Plamondon S, Gupta A. et al. Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn’s perineal fistulas. Am J Gastroenterol 2009; 104: 2973-2986
• 186 Yang B, Chen Y, Gu Y. et al. Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease. World J Gastroenterol 2015; 21 (08) 2475-2482
• 187 Van Assche G, Dignass A, Reinisch W. et al. The second European evidence-based Consensus on the diagnosis and management of CrohnCrohn’ss disease: Special situations. J Crohn Colitis 2010; 4: 63-101
• 188 Hukkinen M, Pakarinen M, Piekkala M. et al. Treatment of complex perianal fistulas with seton and infliximab in adolescents with Crohn’s disease. J Crohns Colitis 2014; 8: 756-762
• 189 Haenning A, Staumont G, Lepage B. et al. The results of seton drainage combined with anti-TNFα-therapy for anal fistula in Crohn’s disease. Colorectal Dis 2015; 17: 311-319
• 190 De Groof E, Sahami S, Lucas C. et al. Treatment of perianal fistula in Crohn’s disease: a systematic review and meta-analysis comparing seton drainage and anti-tumour necrosis factor treatment. Colorectal Dis 2016; 18: 667-675
• 191 Lobaton T, Guardiola J, Rodriguez-Moranta F. et al. Comparison of the long-term outcome of two therapeutic strategies for the management of abdominal abscess complicating Crohn’s disease: percutaneous drainage or immediate surgical treatment. Colorectal Dis 2013; 15: 1267-1272
• 192 Parsi M, Lashner B, Achkar J. et al. Type of fistula determines response to infliximab in patients with fistulous Crohn’s disease. Am J Gastroenterol 2004; 99: 445-459
• 193 Colombel JF, Schwartz D, Sandborn W. et al. Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut 2009; 58: 940-948
• 194 Amiot A, Setakhr V, Seksik P. et al. Long-term outcome of enterocutaneous fistula in patients with Crohn’s disease treated with anti-TNF therapy: a cohort study from the GETAID. Am J Gastroenterol 2014; 109: 1443-1449
• 195 Nguyen D, Sandborn W, Loftus EJr. et al. Similar outcomes of surgical and medical treatment of intra-abdominal abscesses in patients with Crohn's disease. Clin Gastroenterol Hepatol 2012; 10: 400-404
• 196 Spinelli A, Correale C, Szabo H. et al. Intestinal fibrosis in Crohn’s disease: medical treatment or surgery?. Curr Drug Targets 2010; 11: 242-248
• 197 Cosnes J, Gower-Rousseau C, Seksik P. et al. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 1406: 1785-1794
• 198 Peyrin-Biroulet L, Loftus E, Colombel J. et al. The natural history of adult Crohn’s disease in population-based cohorts. Am J Gastroenterol 2010; 105: 289-297
• 199 Panes J, Bouhnik Y, Reinisch W. et al. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis 2013; 7: 556-585
• 200 Fornasa F, Benassuti C, Benazzoti L. Role of Magnetic Resonance Enterography in Differentiating between Fibrotic and Active Inflammatory Small Bowel Stenosis in Patients with Crohn’s Disease. J Clin Imaging Sci 2011; 1: 35 . doi:10.4103/2156–7514.82339
• 201 Holtmann M, Wanitschke R, Helisch A. et al. Anti-TNF antibodies in the treatment of inflammatory intestinal stenoses in Crohn’s disease. Z Gastroenterol 2003; 41: 11-17
• 202 D’Haens G, Van Deventer S, Van Hogezand R. et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn’s disease: a European multicenter trial. Gastroenterology 1999; 116: 1029-1034
• 203 Toy LS, Scherl EJ, Kornbluth A. et al. Complete bowel obstruction following initial response to infliximab therapy for Crohn’s disease: a series of newly described complication. Gastroenterology 2000; 118: A569
• 204 Vasilopoulos S, Kugathasan S, Saeian K. et al. Intestinal strictures complicating initially successful infliximab treatment for luminal Crohn’s disease. Am J Gastroenterol 2000; 95: 2503
• 205 Sou S, Matsui T, Yao T. et al. Clinical and endoscopic healing after infliximab treatment in patients with Crohn’s disease. Digestive Endoscopy 2006; 18: 29-33
• 206 Lichtenstein G, Olson A, Bao W. et al. Infliximab treatment 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: 254-255
• 207 Lichtenstein GR, Olson A, Travers A. 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
• 208 Condino G, Calabrese E, Zorzi F. et al. Anti-TNF-alpha treatments and obstructive symptoms in Crohn’s disease: a prospective study. Dig Liver Dis 2013; 45: 258-262
• 209 Zorzi F, Zuzzi S, Onali S. et al. Efficacy and safety of infliximab and adalimumab in Crohn’s disease: a single centre study. Aliment Pharmacol Ther 2012; 35: 1397-1407
• 210 Matsumoto T, Iida M, Motoyo 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
• 211 Ono Y, Hirai F, Matsui T. et al. Value of concomitant endoscopic balloon dilation for intestinal stricture during long-term infliximab therapy in patients with Crohn’s disease. Dig Endosc 2012; 24: 432-438
• 212 Brochard C, Siproudhis l, Wallenhorst T. et al. Anorectal stricture in 102 patients with Crohn’s disease: natural history in the era of biologics. Aliment Pharmacol Ther 2014; 40: 796-803
• 213 Lovasz BD, Lakatos L, Golovics PA. et al. Risk of colorectal cancer in Crohn’s disease patients with colonic involvement and stenosing disease in a population-based cohort from Hungary. J Gastrointestin Liver Dis 2013; 22: 265-268
• 214 Schoepfer AM, Safroneeva E, Vavricka SR. et al. Treatment of fibrostenotic and fistulizing Crohn’s disease. Digestion 2012; 86 (Suppl. 01) 23-27
• 215 Rieder F, Zimmermann EM, Remzi FH. et al. Crohn’s disease complicated by strictures. Gut 2013; 62: 1072-1084
• 216 Freling E, Baumann C, Cuny J. et al. Cumulative incidence of, risk factors for, and outcome of dermatological complications of ant-TNF therapy in inflammatory bowel disease: a 14-year experience. Am J Gastroenterol 2015; 110: 1186-1196
• 217 Flendrie M, Wissers WH, Creemers MC. et al. Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: a prospective study. Arthritis Res Ther 2005; 7: 666-676
• 218 Lee H, Song I, Friedrich M. et al. Cutaneous side effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol 2007; 156: 486-491
• 219 Hutfless S, Fireman B, Kane S. et al. Screening differences and risk of cervical cancer in inflammatory bowel disease. Aliment Pharmacol Ther 2008; 28: 598-605
• 220 Mocci G, Marzo M, Papa A. et al. Dermatological adverse reactions during anti-TNF treatments: Focus on inflammatory bowel disease. J Crohn´s Colitis 2013; 7: 769-779
• 221 Moscandrew M, Mahadevan U, Kane S. General health maintenance in IBD. Inflamm Bowel Dis 2009; 15: 1399-1408
• 222 Williams C, Peyrin-Biroulet L, Ford A. Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-alpha therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2014; 39: 447-458
• 223 Peyrin-Biroulet L, Khosrotehrani K, Carrat F. et al. Incresed risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology 2011; 141: 1621-1628
• 224 Mercer L, Askling J, Raaschou P. et al. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis 2017; 76: 386-391
• 225 Raaschou P, Simard JF, Asker HagelbergC. et al. ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ 2016; 352: i262 . doi:10.1136/bmj.i262
• 226 Raaschou P, Simard JF, Holmqvist M. et al. ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ 2013; 346: f1939 . doi:10.1136/bmj.f1939
• 227 Schmidt E, Wetter DA, Ferguson SB. et al. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-alpha inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol 2012; 67: e179-e185
• 228 Andisani G, Marzo M, Celleno L. et al. Development of psoriasis scalp with alopecia during treatment of Crohn´s disease with infliximab and rapid response to both diseases to ustekinumab. Eur Rev Med Pharmacol Sci 2013; 17: 2831-2836
• 229 Stoffel E, Maier H, Riedl E. et al. Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics. Br J Dermatol 2017;
• 230 Marzano AV, Tavecchio S, Berti E. et al. Paradoxical autoinflammatory skin reaction to tumor necrosis factor alpha blockers manifesting as amicrobial pustulosis of the folds in patients with inflammatory bowel diseases. Medicine 2015; 94: e1818 . doi:10.1097/MD.0000000000001818
• 231 Lee HY, Pelivani N, Beltraminelli H. et al. Amicrobial pustulosis-like rash in a patient with Crohn´s disease under anti-TNF-alpha blocker. Dermatology 2011; 222: 304-310
• 232 Lichtenstein L, Ron Y, Kivity S. et al. Infliximab-Related Infusion Reactions: Systematic Review. J Crohns Colitis 2015; 9: 806-815
• 233 Yoo DH, Hrycaj P, Miranda P. et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013; 72: 1613-1620
• 234 Duron C, Goutte M, Pereira B. et al. Factors influencing acute infusion reactions in inflammatory bowel disease patients treated with infliximab in the era of scheduled maintenance therapy. Eur J Gastroenterol Hepatol 2015; 27: 705-711
• 235 Cheifetz A, Smedley M, Martin S. et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol 2003; 98: 1315-1324
• 236 Vultaggio A, Matucci A, Nencini F. et al. Anti-infliximab IgE and non-IgE antibodies and induction of infusion-related severe anaphylactic reactions. Allergy 2010; 65: 657-661
• 237 Matucci A, Pratesi S, Petroni G. et al. Allergological in vitro and in vivo evaluation of patients with hypersensitivity reactions to infliximab. Clin Exp Allergy 2013; 43: 659-664
• 238 O’Meara S, Nanda K, Moss AC. Antibodies to infliximab and risk of infusion reactions in patients with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2014; 20: 1-6
• 239 Hanauer SB, Wagner C, Bala M. et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2004; 2: 542-553
• 240 Steenholdt C, Svenson M, Bendtzen K. et al. Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 34: 51-58
• 241 Hanauer S, Feagan B, Lichtenstein G. et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541-1549
• 242 Cheifetz A, Mayer L. Monoclonal antibodies, immunogenicity, and associated infusion reactions. Mt Sinai J Med 2005; 72: 250-256
• 243 Vermeire S, Van Assche G, Rutgeerts P. Serum sickness, encephalitis and other complications of anti-cytokine therapy. Best Pract Res Clin Gastroenterol 2009; 23: 101-112
• 244 Panaccione R, Colombel JF, Sandborn W. et al. Adalimumab maintains remission of Crohn’s disease after up to 4 years of treatment: data from CHARM and ADHERE. Aliment Pharmacol Ther 2013; 38: 1236-1247
• 245 Watanabe M, Hibi T, Mostafa NM. et al. Long-term safety and efficacy of adalimumab in Japanese patients with moderate to severe Crohn’s disease. J Crohns Colitis 2014; 8: 1407-1416
• 246 Schreiber S, Reinisch W, Colombel JF. et al. Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn’s disease. J Crohns Colitis 2013; 7: 213-221
• 247 Mocko P, Kawalec P, Pilc A. Safety Profile of Biologic Drugs in the Treatment of Inflammatory Bowel Diseases: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials. Clin Drug Investig 2016;
• 248 Takase K, Horton S, Ganesha A. et al. What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort. Ann Rheum Dis 2014; 73: 1695-1699
• 249 Wetter D, Davis M. Lupus-like syndrome sttributable to snti—Tumor Necrosis Factor α-therapy in 14 patients during an 8-Year period at Mayo Clinic. Mayo Clin Proc 2009; 84: 979-984
• 250 Williams V, Cohen P. TNF alpha antagonist-induced lupus-like syndrome: report and review of the literature with implications for treatment with alternative TNF alpha antagonists. Int J Dermatol 2011; 50: 619-625
• 251 Rang E, Brooke B, Hermon-Taylor J. Association of ulcerative colitis with multiple sclerosis. Lancet 1982; 2: 555
• 252 Kimura K, Hunter SF, Thollander MS. et al. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc 2000; 75: 902-906
• 253 Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology 2005; 129: 827-836
• 254 Cohen R, Robinson JrD, Paramore C. et al. Autoimmune disease concomitance among inflammatory bowel disease patients in the United States, 2001–2002. Inflamm Bowel Dis 2008; 14: 738-743
• 255 Andersen NN, Caspersen S, Jess T. et al. Occurrence of demyelinating diseases after anti-TNFα-treatment of inflammatory bowel disease: a Danish Crohn Colitis Database study. J Crohn Colitis 2008; 2: 304-309
• 256 Van Oosten BW, Barkhof F, Truyen L. et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 1996; 47: 1531-1534
• 257 Desai S, Furst D. Problems encountered during anti-tumour necrosis factor therapy. Best Pract Res Clin Rheumatol 2006; 20: 757-790
• 258 Thomas C, Einshenker B, Sandborn W. Demyelinating during anti-tumor necrosis factor alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004; 10: 28-31
• 259 Lees C, Ali A, Thompson A. et al. The safety-profile of anti-tumor necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther 2009; 29: 286-297
• 260 Hansen RA, Gartlehner G, Powell GE. et al. Serious adverse events with infliximab: analysis of spontaneously reported adverse events. Clin Gastroenterol Hepatol 2007; 5: 729-735
• 261 Mohan N, Edwards ET, Cupps T. et al. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritis. Arthritis Rheum 2001; 44: 2862-2869
• 262 Fernández-Espartero MC, Pérez-Zafrilla B, Naranjo A. et al. and BIOBADASER Study Group. Demyelinating 2011; 40: 330-337
• 263 Deepak P, Stobaugh D, Sherid M. et al. Neurological events with tumour necrosis factor alpha inhibitors reported to the Food and Drug Administration Adverse Event Reporting System. Aliment Pharmacol Ther 2013; 38: 388-396
• 264 Kay J, Fleischmann R, Keystone E. et al. Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis 2015; 74: 538-546
• 265 Kristensen S, Ahlehoff O, Lindhardsen J. et al. Inflammatory bowel disease is associated with an increased risk of hospitalization for heart failure: a Danish Nationwide Cohort study. Circ Heart Fail 2014; 7: 717-722
• 266 Dregan A, Charlton J, Chowienczyk P. et al. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study. Circulation 2014; 130: 837-844
• 267 Andersen NN, Jess T. Risk of cardiovascular disease in inflammatory bowel disease. World J Gastrointest Pathophysiol 2014; 5: 359-365
• 268 Chung E, Packer M, Lo KH. et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α-in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Heart Failure (ATTACH) trial. Circulation 2003; 107: 3133-4310
• 269 Singh J, Furst D, Bharat A. et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res 2012; 64: 625-639
• 270 Kwon H, Cote T, Cuffe M. et al. Case reports of heart failure after therapy with tumor necrosis factor antagonist. Ann Int Med 2003; 138: 807-811
• 271 Lazzerini PE, Acampa M, Hammoud M. et al. Arrhythmic risk during acute infusion of infliximab: a prospective, single-blind, placebo-controlled, crossover study in patients with chronic arthritis. J Rheumatol 2008; 35: 1958-1965
• 272 Mendes F, Levy C, Enders F. et al. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. Am J Gastroenterol 2007; 102: 344-350
• 273 Pagnini C, Arseneau K, Cominelli F. Safety considerations when using anti-TNFa therapy to treat Crohn’s disease. Expert Opin Drug Saf 2015; 14: 31-44
• 274 Hagel S, Bruns T, Theis B. et al. Subacute liver failure induced by adalimumab. Int J Clin Pharmacol Ther 2011; 49: 38-40
• 275 Adar T, Mizrahi M, Pappo O. et al. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol 2010; 44: e20-e22
• 276 Kim E, Bressler B, Schaeffer DF. et al. Severe cholestasis due to adalimumab in a Crohn’s disease patient. World J Hepatol 2013; 5: 592-595
• 277 Salar A, Bessa X, Muñiz E. et al. Infliximab and adalimumab-induced thrombocytopenia in a woman with colonic Crohn’s disease. Gut 2007; 56: 1169-1170
• 278 Favalli EG, Varenna M, Sinigaglia L. Drug-induced agranulocy- tosis during treatment with infliximab in enteropathic spondy- larthropathy. Clin Exp Rheumatol 2005; 23: 247-250
• 279 Bessissow T, Renard M, Hoffman I. et al. Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy. Aliment Pharmacol Ther 2012; 36: 312-323
• 280 Rajakulendran S, Gadsby K, Allen D. et al. Neutropenia while receiving anti-tumour necrosis factor treatment for rheumatoid arthritis. Ann Rheum Dis 2006; 65: 1678-1679
• 281 Beaugerie L, Itzkowitz S. Cancers complicating inflammatory bowel disease. N Engl J Med 2015; 372: 1441-1452
• 282 Lichtenstein G, Feagan B, Cohen R. et al. Drug therapies and the risk of malignancy in crohn`s disease: results from the TREAT Registry. Am J Gastroenterol 2014; 109: 212-223
• 283 Kappelman M, Farkas D, Long M. et al. Risk of cancer in patients with inflammatory bowel disease: a nationwide population-based cohort study with 30 years of follow-up evaluation. Clin Gastroenterol Hepatol 2014; 12: 265-273
• 284 Beaugerie L, Carrat F, Colombel JF. et al. Risk of new or recurrent cancer under immunsuppressiv therapy in patients with IBD and previous cancer. Gut 2014; 63: 1416-1423
• 285 Singh S, Nagpal S, Murad M. et al. Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clinical Gastroenterology and Hepatology 2014; 12: 210-218
• 286 Bernheim O, Colombel JF, Ullman T. et al. The management of immunosuppression in patients with inflammatory bowel disease and cancer. Gut 2013; 62: 1523-1528
• 287 Dulai P, Siegel C, Colombel JF. et al. Systematic review: monotherapy with antitumor necrosis factor agents versus combination therapy with an immunosuppressive for IBD. Gut 2014; 63: 1843-1853
• 288 Kotlyar D, Lewis J, Beaugerie L. et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol 2015; 13: 847-858
• 289 Lopez A, Mounier M, Bouvier A. et al. CESAME Study Group. Increased risk of akute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease. Clin Gastroenterol Hepatol 2014; 12: 1324-1329
• 290 Deepak P, Sifuentes H, Sherid M. et al. T-cell Non-Hodgkin`s Lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-) inhibitors: results of the REFURBISH study. Am J Gastroenterol 2013; 108: 99-105
• 291 Herrinton L, Liu L, Weng X. et al. Role of thiopurine and anti-TNF Therapy in Lymphoma in inflammatory bowel disease. Am J Gastroenterol 2011; 106: 2146-2153
• 292 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: 1679-1686
• 293 Mercer L, Regierer A, Mariette X. et al. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project. Ann Rheum Dis 2017; 76: 2025-2030
• 294 Thai A, Prindiville T. Hepatosplenic T-cell lymphoma and inflammatory bowel disease. J Crohns Colitis 2010; 4: 511-522
• 295 Kotlyar D, Osterman M, Diamond R. 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: 36-41
• 296 Nyboe AndersenN, Pasternak B, Basit S. et al. Association between tumor necrosis factor- antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA 2014; 311: 2406-2413
• 297 Osterman M, Sandborn W, Colombel JF. et al. Increased risk of malignancy with adalimumab combination therapy, compared with monotherapy, for crohn`s disease. Gastroenterology 2014; 146: 941-949
• 298 Rungoe C, Simonsen J, Riis L. et al. Inflammatory bowel disease and cervical neoplasia: a poulation-based nationwid cohort study. Clin Gastroenterol Hepatol 2015; 13: 693-700
• 299 Long M, Martin C, Pipkin C. et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012; 143: 390-399
• 300 Siegel C, Marden S, Persing S. et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunmodulator therapy for the treatment of Crohn`s disease: a meta-analysis. Clin Gastroenterol Hepatol 2009; 7: 874-881
• 301 Strangfeld A, Hierse F, Rau R. et al. Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther 2010; 12: R5
• 302 Silva-Fernández L, Lunt M, Kearsley-Fleet L. et al. The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis. Rheumatology 2016; 55: 2033-2039
• 303 Raaschou P, Frisell T, Askling J. TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study. Ann Rheum Dis 2015; 74: 2137-2143
• 304 Phillips C, Zeringue A, McDonald J. et al. Tumor Necrosis Factor Inhibition and Head and Neck Cancer Recurrence and Death in Rheumatoid Arthritis. PLoS One 2015; 10: e0143286
• 305 Wiedenmann B, Malfertheiner P, Friess H. et al. A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J Support Oncol 2008; 6: 18-25
• 306 Jatoi A, Ritter HL, Dueck A. et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9). Lung Cancer 2010; 68: 234-239
• 307 Monk J, Phillips G, Waite R. et al. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. J Clin Oncol 2006; 24: 1852-1859
• 308 Annese V, Beaugerie L, Egan L. et al. European evidence-based consensus: inflammatory bowel disease and malignancies. J Crohns Colitis 2015; 10: 945-965
• 309 Molodecky NA, Soon IS, Rabi DM. et al. Increasing incidence and prevalence oft he inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142: 46-54
• 310 Hassid B, Mahadevan U. The use of biologic therapy in pregnancy: a gastroenterologist’s perspective. Curr Opin Rheumatol 2014; 26: 347-353
• 311 Narula N, Al-Dabbagh R, Dhillon A. et al. Anti-TNF(therapies are safe during pregnancy in women with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2014; 20: 1862-1869
• 312 Deepak P, Stobaugh D. Maternal and foetal adverse events with tumour necrosis factor-alpha inhibitors in inflammatory bowel disease. Aliment Pharmacol Ther 2014; 40: 1035-1043
• 313 Zelinkova Z, de Haar C, de Ridder L. et al. High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy. Aliment Pharmacol Ther 2011; 33: 1053-1058
• 314 Mahadevan U, Wolf D, Dubinsky M. et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol 2013; 11: 286-292
• 315 Vasiliauskas E, Church J, Silverman N. et al. Case report: Evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterolo Hepatol 2006; 4: 1255-1258
• 316 Bortolik M, Duricova D, Machkova N. et al. Impact of anti-tumor necrosis factor alpha antibodies administered tp pregnant women with inflammatory bowel disease on long-term outcome of exposed children. Inflamm Bowel Dis 2014; 20: 495-501
• 317 Cheent K, Nolan J, Shariq S. et al. Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohn’s Colitis 2010; 4: 603-605
• 318 Guiddir T, Fremond M, Triki T. et al. Anti-TNF-alpha therapy may cause neonatal neutropenia. Pediatrics 2014; 134: e1189-e1193
• 319 van der Woude CJ, Ardizzone S, Bengtson MB. et al. The second European evidence-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 2015; 9: 107-124
• 320 de Lima A, Zelinkova Z, van der Ent C. et al. Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety. Gut 2016; 65: 1261-1268
• 321 Nguyen G, Seow C, Maxwell C. et al. The Toronto Consensus statements for the management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology 2016; 150: 734-757
• 322 Julsgaard M, Christensen L, Gibson P. et al. Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection. Gastroenterology 2016; 151: 110-119
• 323 Johnson D, Jones K, Chambers C. et al. Pregnancy Outcomes in Women Exposed to Adalimumab: the OTIS Autoimmune Diseases in Pregnancy Project. Gastroenterology 2009; 136 (Suppl. 01) A27
• 324 Chambers C, Johnson D, Luo Y. et al. Pregnancy outcome in women treated with adalimumab for the treatment of rheumatoid arthritis. An update on the OTIS autoimmune diseases in pregnancy project. Gastroenterology 2015; 148 (Suppl. 01) S-405
• 325 Martin P, Oneda S, Treacy G. Effects of an anti-TNF-alpha monoclonal antibody, administered throughout pregnancy and lactation, on the development of the macaque immune system. Am J Reprod Immunol 2007; 58: 138-149
• 326 Arsenescu R, Arsenescu V, deVillers W. TNF-a and the development of the neonatal immune system: implications for inhibitor use in pregnancy. Am J Gastroenterol 2011; 106: 559-562
• 327 Mahadevan U, Martin C, Sandler R. et al. PIANO: A 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology 2012; 142 (Suppl. 01) S149
• 328 Mahadevan U, Martin C, Dubinsky M. et al. Exposure to anti-TNF α-therapy in the third trimester of pregnancy is not associated with increased adverse outcomes: results from the PIANO registry. Gastroenterology 2014; 146 (Suppl. 01) S170
• 329 Sands B, Cuffari C, Katz J. et al. Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 2004; 10: 677-692
• 330 Melmed G. Vaccination strategies for patients with inflammatory bowel disease on immunomodulators and biologics. Inflamm Bowel Dis 2009; 15: 1410-1416
• 331 Ben-Horin S, Yavzori M, Kopylov U. et al. Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. J Crohn’s Colitis 2011; 5: 555-558
• 332 Fritzsche J, Pilch A, Mury D. et al. Infliximab and Adalimumab use during breastfeeding. J Clin Gastroenterol 2012; 46: 718-719
• 333 Grosen A, Julsgaard M, Kelsen J. et al. Infliximab concentrations in the milk of nursing mothers with inflammatory bowel disease. J Crohn Colitis 2014; 8: 175-176
• 334 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
• 335 Matro R, Martin C, Wolf D. et al. Detection of biologic agents in breast milk and implication for infection, growth and development in infants born to women with inflammatory bowel disease: results from the PIANO registry. Gastroenterology 2015; 148: S141
• 336 Penn I. The effect of immunosuppression on pre-existing cancers. Transplantation 1993; 55: 742-747