Advertisement

Therapie mit monoklonalen Antikörpern in der Gastroenterologie

  • Philipp Dobsch
  • Bernhard Michels
  • Martina Müller-Schilling
  • Arne KandulskiEmail author
Schwerpunkt: Monoklonale Antikörper
  • 55 Downloads

Zusammenfassung

Monoklonale Antikörper finden im klinischen Alltag vielfältigen Einsatz in der Therapie verschiedener gastroenterologischer onkologischer und infektiologischer Erkrankungen des Gastrointestinaltrakts. Die Hauptindikationen liegen in der Behandlung chronisch-entzündlicher Darmerkrankungen und in der Onkologie. Ein neues Einsatzgebiet in der Infektiologie ist die Therapie der rekurrierenden Clostridium-difficile-Kolitis. In der Nomenklatur der monoklonalen Antikörper weisen die Endungen der Substanzen auf die Herstellung bzw. den Grad der „Humanisierung“ der jeweiligen Antikörper hin („umab“: vollhumaner, rekombinanter Antikörper; „ximab“: chimärer Antikörper mit variabler muriner Domäne). Monoklonale therapeutische Antikörper sind in der Therapie der chronisch-entzündlichen Darmerkrankungen vor allem gegen Ziele der inflammatorischen Kaskade (Tumor-Nekrose-Faktor‑α, Interleukin-12 und -23; α4β7-Integrine) sowie in der Onkologie gegen integrale Bestandteile von Signalwegen der Proliferation und/oder Neovaskularisation gerichtet (unter anderem gegen den „vascular endothelial growth factor“ [VEGF], VEGF-Rezeptor, „epidermal growth factor receptor“ und HER2/neu). Der vorliegende Übersichtsbeitrag soll einen umfassenden Überblick über die therapeutischen Einsatzmöglichkeiten monoklonaler Antikörper bei gastroenterologischen Erkrankungen geben.

Schlüsselwörter

Molekular zielgerichtete Therapie Kolorektales Karzinom Magenkarzinom Morbus Crohn Colitis ulcerosa 

Therapeutic regimens using monoclonal antibodies in gastroenterology

Abstract

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of “humanization” of the respective antibodies (“umab”: fully human, recombinant antibody; “ximab”: chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor‑α, interleukin-12 and -23; α4β7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.

Keywords

Molecular targeted therapy Colorectal neoplasms Stomach neoplasms Crohn disease Colitis, ulcerative 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

P. Dobsch, B. Michels, M. Müller-Schilling und A. Kandulski geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Literatur

  1. 1.
    Bang Y‑J, van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang Y‑K (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697.  https://doi.org/10.1016/S0140-6736(10)61121-X CrossRefGoogle Scholar
  2. 2.
    Schmiegel W, Buchberger B, Follmann M, Graeven U, Heinemann V, Langer T, Nothacker M, Porschen R, Rödel C, Rösch T, Schmitt W, Wesselmann S, Pox C (2017) S3-Leitlinie – Kolorektales Karzinom. Z Gastroenterol 55(12):1344–1498.  https://doi.org/10.1055/s-0043-121106 CrossRefGoogle Scholar
  3. 3.
    van Cutsem E, Cervantes A, Adam R, Sobrero A, van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D’Hoore A, Diaz-Rubio E, Douillard J‑Y, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne C‑H, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJG, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27(8):1386–1422.  https://doi.org/10.1093/annonc/mdw235 CrossRefGoogle Scholar
  4. 4.
    Arnold D, Lueza B, Douillard J‑Y, Peeters M, Lenz H‑J, Venook A, Heinemann V, van Cutsem E, Pignon J‑P, Tabernero J, Cervantes A, Ciardiello F (2017) Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol 28(8):1713–1729.  https://doi.org/10.1093/annonc/mdx175 CrossRefGoogle Scholar
  5. 5.
    AIO-KRK-Leitgruppe (2016) Statement der AIO-KRK-Leitgruppe zur Wahl der Erstlinientherapie bei Patienten mit metastasiertem Kolorektalkarzinom ohne Nachweis einer RAS Mutation unter Berücksichtigung der primären Tumorlokalisation: Update 31. Oktober 2016Google Scholar
  6. 6.
    Pox C, Aretz S, Bischoff SC, Graeven U, Hass M, Heußner P, Hohenberger W, Holstege A, Hübner J, Kolligs F, Kreis M, Lux P, Ockenga J, Porschen R, Post S, Rahner N, Reinacher-Schick A, Riemann JF, Sauer R, Sieg A, Scheppach W, Schmitt W, Schmoll HJ, Schulmann K, Tannapfel A, Schmiegel W (2013) S3-Leitlinie Kolorektales Karzinom Version 1.0 – Juni 2013 AWMF-Registernummer: 021/007OL. Z Gastroenterol 51(8):753–854.  https://doi.org/10.1055/s-0033-1350264 CrossRefGoogle Scholar
  7. 7.
    Goey KKH, Elias SG, van Tinteren H, Laclé MM, Willems SM, Offerhaus GJA, de Leng WWJ, Strengman E, ten Tije AJ, Creemers G‑JM, van der Velden A, de Jongh FE, Erdkamp FLG, Tanis BC, Punt CJA, Koopman M (2017) Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study. Ann Oncol 28(9):2128–2134.  https://doi.org/10.1093/annonc/mdx322 CrossRefGoogle Scholar
  8. 8.
    Pietrantonio F, Morano F, Corallo S, Miceli R, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Bergamo F, Sartore-Bianchi A, Tampellini M, Racca P, Clavarezza M, Berenato R, Caporale M, Antista M, Niger M, Smiroldo V, Murialdo R, Zaniboni A, Adamo V, Tomasello G, Giordano M, Petrelli F, Longarini R, Cinieri S, Falcone A, Zagonel V, Di Bartolomeo M, de Braud F (2019) Maintenance therapy with panitumumab alone vs panitumumab plus fluorouracil-leucovorin in patients with RAS wild-type metastatic colorectal cancer: a phase 2 randomized clinical trial. JAMA Oncol.  https://doi.org/10.1001/jamaoncol.2019.1467 Google Scholar
  9. 9.
    Nagata N, Mishima H, Kurosawa S, Oba K, Sakamoto J (2017) mFOLFOX6 plus panitumumab versus 5‑FU/LV plus panitumumab after six cycles of frontline mFOLFOX6 plus panitumumab: a randomized phase II study of patients with unresectable or advanced/recurrent, RAS wild-type colorectal carcinoma (SAPPHIRE)-study design and rationale. Clin Colorectal Cancer 16(2):154.  https://doi.org/10.1016/j.clcc.2017.02.001 CrossRefGoogle Scholar
  10. 10.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342.  https://doi.org/10.1056/NEJMoa032691 CrossRefGoogle Scholar
  11. 11.
    Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25(12):1539–1544.  https://doi.org/10.1200/JCO.2006.09.6305 CrossRefGoogle Scholar
  12. 12.
  13. 13.
    Wilke H, Muro K, van Cutsem E, Oh S‑C, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim T‑Y, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol 15(11):1224–1235.  https://doi.org/10.1016/S1470-2045(14)70420-6 CrossRefGoogle Scholar
  14. 14.
    Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J (2014) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383(9911):31–39.  https://doi.org/10.1016/S0140-6736(13)61719-5 CrossRefGoogle Scholar
  15. 15.
    Zhu AX, Kang Y‑K, Yen C‑J, Finn RS, Galle PR, Llovet JM, Assenat E, Brandi G, Pracht M, Lim HY, Rau K‑M, Motomura K, Ohno I, Merle P, Daniele B, Shin DB, Gerken G, Borg C, Hiriart J‑B, Okusaka T, Morimoto M, Hsu Y, Abada PB, Kudo M (2019) Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α‑fetoprotein concentrations (REACH-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Oncology 20(2):282–296.  https://doi.org/10.1016/S1470-2045(18)30937-9 Google Scholar
  16. 16.
    Zhu AX, Park JO, Ryoo B‑Y, Yen C‑J, Poon R, Pastorelli D, Blanc J‑F, Chung HC, Baron AD, Pfiffer TEF, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang S‑C, Abada PB, Yang L, Schwartz JD, Kudo M (2015) Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): A randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 16(7):859–870.  https://doi.org/10.1016/S1470-2045(15)00050-9 CrossRefGoogle Scholar
  17. 17.
    Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu T‑E, Portnoy DC, van Cutsem E, Grothey A, Prausová J, Garcia-Alfonso P, Yamazaki K, Clingan PR, Lonardi S, Kim TW, Simms L, Chang S‑C, Nasroulah F (2015) Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): A randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 16(5):499–508.  https://doi.org/10.1016/S1470-2045 CrossRefGoogle Scholar
  18. 18.
    Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345.  https://doi.org/10.1056/NEJMoa033025 CrossRefGoogle Scholar
  19. 19.
    Heinemann V, v. Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S‑E, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes H‑G, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol 15(10):1065–1075.  https://doi.org/10.1016/S1470-2045(14)70330-4 CrossRefGoogle Scholar
  20. 20.
    Venook AP, Niedzwiecki D, Lenz H‑J, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O’Neil BH, Atkins JN, Berry S, Polite BN, O’Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB, Mulkerin DL, Mayer RJ, Blanke C (2017) Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic Colorectal cancer: a randomized clinical trial. JAMA 317(23):2392–2401.  https://doi.org/10.1001/jama.2017.7105 CrossRefGoogle Scholar
  21. 21.
    Aljehani MA, Morgan JW, Guthrie LA, Jabo B, Ramadan M, Bahjri K, Lum SS, Selleck M, Reeves ME, Garberoglio C, Senthil M (2018) Association of primary tumor site with mortality in patients receiving bevacizumab and cetuximab for metastatic colorectal cancer. JAMA Surg 153(1):60–67.  https://doi.org/10.1001/jamasurg.2017.3466 CrossRefGoogle Scholar
  22. 22.
    van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon J‑L, van Laethem J‑L, Maurel J, Richardson G, Wolf M, Amado RG (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664.  https://doi.org/10.1200/JCO.2006.08.1620 CrossRefGoogle Scholar
  23. 23.
    Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJA, Strickland AH, Wilson G, Ciuleanu T‑E, Roman L, van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28(31):4706–4713.  https://doi.org/10.1200/JCO.2009.27.6055 CrossRefGoogle Scholar
  24. 24.
    Douillard J‑Y, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon J‑L, Rother M, Oliner KS, Wolf M, Gansert J (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol 28(31):4697–4705.  https://doi.org/10.1200/JCO.2009.27.4860 CrossRefGoogle Scholar
  25. 25.
    Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon J‑L, Hecht JR, Yu H, Oliner KS, Go WYPEAK (2014) A randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol 32(21):2240–2247.  https://doi.org/10.1200/JCO.2013.53.2473 CrossRefGoogle Scholar
  26. 26.
    Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D (2016) Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(suppl 5):v38–v49.  https://doi.org/10.1093/annonc/mdw350 CrossRefGoogle Scholar
  27. 27.
    The Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517):202–209.  https://doi.org/10.1038/nature13480 CrossRefGoogle Scholar
  28. 28.
    Preiß JC, Bokemeyer B, Buhr HJ, Dignaß A, Häuser W, Hartmann F, Herrlinger KR, Kaltz B, Kienle P, Kruis W, Kucharzik T, Langhorst J, Schreiber S, Siegmund B, Stallmach A, Stange EF, Stein J, Hoffmann JC (2014) Aktualisierte S3-Leitlinie-„Diagnostik und Therapie des Morbus Crohn“ 2014 [Updated German clinical practice guideline on „Diagnosis and treatment of Crohn’s disease“ 2014. Z Gastroenterol 52(12):1431–1484.  https://doi.org/10.1055/s-0034-1385199 CrossRefGoogle Scholar
  29. 29.
    Gomollón F, Dignass A, Annese V, Tilg H, van Assche G, Lindsay JO, Peyrin-Biroulet L, Cullen GJ, Daperno M, Kucharzik T, Rieder F, Almer S, Armuzzi A, Harbord M, Langhorst J, Sans M, Chowers Y, Fiorino G, Juillerat P, Mantzaris GJ, Rizzello F, Vavricka S, Gionchetti P (2017) 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis 11(1):3–25.  https://doi.org/10.1093/ecco-jcc/jjw168 CrossRefGoogle Scholar
  30. 30.
    Lindhaus C, Tittelbach J, Elsner P (2017) Cutaneous side effects of TNF-alpha inhibitors. J Dtsch Dermatol Ges 15(3):281–288.  https://doi.org/10.1111/ddg.13200 Google Scholar
  31. 31.
    Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P (2010) Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 362(15):1383–1395.  https://doi.org/10.1056/NEJMoa0904492 CrossRefGoogle Scholar
  32. 32.
    Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ (1997) 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 337(15):1029–1035.  https://doi.org/10.1056/NEJM199710093371502 CrossRefGoogle Scholar
  33. 33.
    Shivashankar R, Pardi DS (2017) Use of anti-tumor necrosis factors and anti-Integrins in the treatment of Crohn’s disease. Gastroenterol Clin North Am 46(3):589–601.  https://doi.org/10.1016/j.gtc.2017.05.012 CrossRefGoogle Scholar
  34. 34.
    Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P (2002) Maintenance infliximab for Crohn’s disease: The ACCENT I randomised trial. Lancet 359(9317):1541–1549.  https://doi.org/10.1016/S0140-6736(02)08512-4 CrossRefGoogle Scholar
  35. 35.
    Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Hanauer SB (2004) Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology 126(2):402–413.  https://doi.org/10.1053/j.gastro.2003.11.014 CrossRefGoogle Scholar
  36. 36.
    Dreesen E, van Stappen T, Ballet V, Peeters M, Compernolle G, Tops S, van Steen K, van Assche G, Ferrante M, Vermeire S, Gils A (2018) Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn’s disease who lose clinical response. Aliment Pharmacol Ther 47(3):346–355.  https://doi.org/10.1111/apt.14452 CrossRefGoogle Scholar
  37. 37.
    Da W, Zhu J, Wang L, Lu Y (2013) Adalimumab for Crohn’s disease after infliximab treatment failure: a systematic review. Eur J Gastroenterol Hepatol 25(8):885–891.  https://doi.org/10.1097/MEG.0b013e32836220ab CrossRefGoogle Scholar
  38. 38.
    Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, Panaccione R, Wolf D, Pollack P (2006) Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC‑I trial. Gastroenterology 130(2):323.  https://doi.org/10.1053/j.gastro.2005.11.030 CrossRefGoogle Scholar
  39. 39.
    Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Colombel J‑F, Panaccione R, D’Haens G, Li J, Rosenfeld MR, Kent JD, Pollack PF (2007) Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med 146(12):829–838.  https://doi.org/10.7326/0003-4819-146-12-200706190-00159 CrossRefGoogle Scholar
  40. 40.
    Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh DG, Panaccione R, Wolf D, Kent JD, Bittle B, Li J, Pollack PF (2007) Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut 56(9):1232–1239.  https://doi.org/10.1136/gut.2006.106781 CrossRefGoogle Scholar
  41. 41.
    Colombel J‑F, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, Schreiber S, Byczkowski D, Li J, Kent JD, Pollack PF (2007) Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 132(1):52–65.  https://doi.org/10.1053/j.gastro.2006.11.041 CrossRefGoogle Scholar
  42. 42.
    Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Willem JS, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353(23):2462–2476.  https://doi.org/10.1056/NEJMoa050516 CrossRefGoogle Scholar
  43. 43.
    Jiang X‑L, Cui H‑F, Gao J, Fan H (2015) Low-dose Infliximab for Induction and Maintenance Treatment in Chinese Patients With Moderate to Severe Active Ulcerative Colitis. J Clin Gastroenterol 49(7):582–588.  https://doi.org/10.1097/MCG.0000000000000319 CrossRefGoogle Scholar
  44. 44.
    Downey C (2016) Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arthritis: a literature review. Int J Rheum Dis 19(6):536–550.  https://doi.org/10.1111/1756-185X.12659 CrossRefGoogle Scholar
  45. 45.
    Toruner M, Loftus EV, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, Colombel J‑F, Egan LJ (2008) Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 134(4):929–936.  https://doi.org/10.1053/j.gastro.2008.01.012 CrossRefGoogle Scholar
  46. 46.
    Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, Cottone M, de Ridder L, Doherty G, Ehehalt R, Esteve M, Katsanos K, Lees CW, Macmahon E, Moreels T, Reinisch W, Tilg H, Tremblay L, Veereman-Wauters G, Viget N, Yazdanpanah Y, Eliakim R, Colombel JF (2014) Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 8(6):443–468.  https://doi.org/10.1016/j.crohns.2013.12.013 CrossRefGoogle Scholar
  47. 47.
    Lapsia S, Koganti S, Spadaro S, Rajapakse R, Chawla A, Bhaduri-McIntosh S (2016) Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation. J Med Virol 88(2):312–318.  https://doi.org/10.1002/jmv.24331 CrossRefGoogle Scholar
  48. 48.
    Shale MJ, Seow CH, Coffin CS, Kaplan GG, Panaccione R, Ghosh S (2010) Review article: Chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease. Aliment Pharmacol Ther 31(1):20–34.  https://doi.org/10.1111/j.1365-2036.2009.04112.x CrossRefGoogle Scholar
  49. 49.
    Yun H, Xie F, Beyl RN, Chen L, Lewis JD, Saag KG, Curtis JR (2017) Risk of hypersensitivity to biologic agents among medicare patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 69(10):1526–1534.  https://doi.org/10.1002/acr.23141 CrossRefGoogle Scholar
  50. 50.
    Hastings R, Ding T, Butt S, Gadsby K, Zhang W, Moots RJ, Deighton C (2010) Neutropenia in patients receiving anti-tumor necrosis factor therapy. Arthritis Care Res 62(6):764–769.  https://doi.org/10.1002/acr.20037 CrossRefGoogle Scholar
  51. 51.
    Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT (2003) Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107(25):3133–3140.  https://doi.org/10.1161/01.CIR.0000077913.60364.D2 CrossRefGoogle Scholar
  52. 52.
    Bye WA, Jairath V, Travis SPL (2017) Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 46(1):3–15.  https://doi.org/10.1111/apt.14075 CrossRefGoogle Scholar
  53. 53.
  54. 54.
  55. 55.
    Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Llurba E, Gris JM (2017) Tumor necrosis factor-alpha and pregnancy: focus on biologics. An updated and comprehensive review. Clin Rev Allergy Immunol 53(1):40–53.  https://doi.org/10.1007/s12016-016-8596-x CrossRefGoogle Scholar
  56. 56.
    van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders AGMGJ, Pedersen N, Selinger C, Sebastian S, Sturm A, Zelinkova Z, Magro F (2015) The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 9(2):107–124.  https://doi.org/10.1093/ecco-jcc/jju006 CrossRefGoogle Scholar
  57. 57.
    Croce E, Hatz C, Jonker EF, Visser LG, Jaeger VK, Bühler S (2017) Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation—a systematic review of randomized trials, observational studies and case reports. Vaccine 35(9):1216–1226.  https://doi.org/10.1016/j.vaccine.2017.01.048 CrossRefGoogle Scholar
  58. 58.
    Annese V, Beaugerie L, Egan L, Biancone L, Bolling C, Brandts C, Dierickx D, Dummer R, Fiorino G, Gornet JM, Higgins P, Katsanos KH, Nissen L, Pellino G, Rogler G, Scaldaferri F, Szymanska E, Eliakim R (2015) European evidence-based consensus: inflammatory bowel disease and malignancies. J Crohns Colitis 9(11):945–965.  https://doi.org/10.1093/ecco-jcc/jjv141 CrossRefGoogle Scholar
  59. 59.
  60. 60.
    Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel J‑F, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A (2013) Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 369(8):711–721.  https://doi.org/10.1056/NEJMoa1215739 CrossRefGoogle Scholar
  61. 61.
    Allegretti JR, Barnes EL, Stevens B, Storm M, Ananthakrishnan A, Yajnik V, Korzenik J (2017) Predictors of clinical response and remission at 1 year among a multicenter cohort of patients with inflammatory bowel disease treated with vedolizumab. Dig Dis Sci 62(6):1590–1596.  https://doi.org/10.1007/s10620-017-4549-3 CrossRefGoogle Scholar
  62. 62.
    Colombel J‑F, Sands BE, Rutgeerts P, Sandborn W, Danese S, D’Haens G, Panaccione R, Loftus EV, Sankoh S, Fox I, Parikh A, Milch C, Abhyankar B, Feagan BG (2017) The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut 66(5):839–851.  https://doi.org/10.1136/gutjnl-2015-311079 CrossRefGoogle Scholar
  63. 63.
    Zelinkova Z, Berakova K, Podmanicky D, Kadleckova B (2017) Placental madCAM1 expression and potential consequences for the treatment with vedolizumab during pregnancy. Gastroenterology 152(5):S764–S765.  https://doi.org/10.1016/S0016-5085(17)32653-7 CrossRefGoogle Scholar
  64. 64.
    Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao L‑L, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel J‑F, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EV, Dieleman LA, Katz S, Rutgeerts P (2016) Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 375(20):1946–1960.  https://doi.org/10.1056/NEJMoa1602773 CrossRefGoogle Scholar
  65. 65.
  66. 66.
    Cortes X, Borrás-Blasco J, Antequera B, Fernandez-Martinez S, Casterá E, Martin S, Molés JR (2017) Ustekinumab therapy for Crohn’s disease during pregnancy: a case report and review of the literature. J Clin Pharm Ther 42(2):234–236.  https://doi.org/10.1111/jcpt.12492 CrossRefGoogle Scholar
  67. 67.
    Panaccione R, Ghosh S, Middleton S, Márquez JR, Scott BB, Flint L, van Hoogstraten HJF, Chen AC, Zheng H, Danese S, Rutgeerts P (2014) Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 146(2):392–400.e3.  https://doi.org/10.1053/j.gastro.2013.10.052 CrossRefGoogle Scholar
  68. 68.
    Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (2018) Aktualisierte S3-Leitlinie Colitis ulcerosa der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) [Updated S3-Guideline Colitis ulcerosa. German Society for Digestive and Metabolic Diseases (DGVS)—AWMF Registry 021/009]. Z Gastroenterol 56(9):1087–1169.  https://doi.org/10.1055/a-0651-8174 CrossRefGoogle Scholar
  69. 69.
  70. 70.
    Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, Kucharzik T, Molnár T, Raine T, Sebastian S, de Sousa HT, Dignass A, Carbonnel F (2017) Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis 11(7):769–784.  https://doi.org/10.1093/ecco-jcc/jjx009 CrossRefGoogle Scholar
  71. 71.
    Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel J‑F, Reinisch W, Gibson PR, Collins J, Järnerot G, Rutgeerts P (2014) Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology 146(1):96–109.e1.  https://doi.org/10.1053/j.gastro.2013.06.010 CrossRefGoogle Scholar
  72. 72.
    Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel J‑F, Sandborn WJ, van Assche G, Axler J, Kim H‑J, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A (2013) Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 369(8):699–710.  https://doi.org/10.1056/NEJMoa1215734 CrossRefGoogle Scholar
  73. 73.
  74. 74.
    Lee Y, Lim WI, Bloom CI, Moore S, Chung E, Marzella N (2017) Bezlotoxumab (Zinplava) for Clostridium Difficile Infection: The First Monoclonal Antibody Approved to Prevent the Recurrence of a Bacterial Infection. P T 42(12):735–738Google Scholar
  75. 75.
    Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, Cornely OA, Rahav G, Bouza E, Lee C, Jenkin G, Jensen W, Kim Y‑S, Yoshida J, Gabryelski L, Pedley A, Eves K, Tipping R, Guris D, Kartsonis N, Dorr M‑B (2017) Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med 376(4):305–317.  https://doi.org/10.1056/NEJMoa1602615 CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • Philipp Dobsch
    • 1
  • Bernhard Michels
    • 1
  • Martina Müller-Schilling
    • 1
  • Arne Kandulski
    • 1
    Email author
  1. 1.Klinik und Poliklinik für Innere Medizin IUniversitätsklinikum RegensburgRegensburgDeutschland

Personalised recommendations