Subscribe to RSS
DOI: 10.1055/a-1585-4026
Chronisch-entzündliche Darmerkrankungen
Inflammatory bowel diseases – therapy update 2022Was ist neu?
Chirurgische Therapie Die Auswertung von Langzeitdaten bestätigt die Gleichwertigkeit der primär chirurgischen vs. medikamentösen (Infliximab) Therapie bei Morbus-Crohn-Patienten mit isoliertem Ileozökalbefall.
Neu zugelassene und sich in später klinischer Entwicklung befindliche Therapien Der selektive JAK-1-Inhibitor Filgotinib ist kürzlich zur Behandlung von Colitis-ulcerosa-Patienten mit mittelschwerer bis schwerer Aktivität zugelassen worden, welche auf eine konventionelle oder biologische Therapie nicht angesprochen haben. Weiterhin ist der S1P-Rezeptor-Modulator Ozanimod, welcher den Abstrom von Lymphozyten aus dem Lymphknoten verhindert, ebenfalls zur Behandlung der genannten Colitis-ulcerosa-Patienten zugelassen worden. Der S1P-Rezeptor-Modulator Etrasimod wird aktuell in einer klinischen Phase-3-Studie bei Colitis ulcerosa getestet und der selektive JAK-1-Inhibitor Upadacitinib dürfte nächstes Jahr bei Colitis ulcerosa zugelassen werden. Zahlreiche IL-23p19-Inhibitoren befinden sich in fortgeschrittenen Studienphasen (Guselkumab, Mirikizumab, Brazikumab) bzw. haben diese bereits beendet (Risankizumab). Deren Zulassung ist zeitnah zu erwarten. Der lokal applizierbare Toll-like-Rezeptor-9-Agonist Cobitolimod könnte zukünftig eine lokal applizierbare Therapieoption bei Patienten mit linksseitiger Colitis ulcerosa darstellen.
Zukünftige therapeutische Herausforderungen Die Positionierung der bereits vorhandenen und zukünftigen Therapieoptionen in unseren Therapiealgorithmus muss noch definiert werden. Hierbei können wir auf Ergebnisse erster Head-to-Head-Studien zurückgreifen und sollten darüber hinaus bei jedem Patienten individuelle Faktoren berücksichtigen. Noch immer fehlen Prädiktoren für die Vorhersage des individuellen Therapieansprechens.
Abstract
Growing insights into the underlying immunopathogenesis of inflammatory bowel diseases (IBD) have led to the advent of targeted therapies, which selectively target pivotal mediators of the inflammatory process. This has enabled us to define and achieve novel therapeutic outcomes to prevent disease-associated complications and halt the progressive course of disease. In addition to already available treatment options, the selective Janus kinase type 1 inhibitor filgotinib and the selective sphingosine-1-phosphate receptor modulator Ozanimod have recently been approved for the treatment of ulcerative colitis patients. Furthermore, positive phase 2/3 induction and maintenance trial results have been reported for representatives of the class of IL-23p19 inhibitors, which are expected to further increase our therapeutic possibilities. All these agents can be applied as first-line or also subsequent treatment options and recent head-to-head trials have helped us to position these substances in our therapeutic algorithm. Nevertheless, there is still the currently unmet clinical need do establish predictive markers of response to identify the subgroup of IBD patients, that have a heightened probability of response to each therapy. In the following, we will give an overview of the recently approved or in late-stage clinical development tested substances and discuss their positioning in our therapeutic armamentarium.
Publication History
Article published online:
15 March 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Ytterberg SR, Bhatt DL, Mikuls TR. et al. ORAL Surveillance Investigators. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med 2022; 386 (04) 316-326
- 2 Agrawal M, Verstockt B. Etrolizumab for ulcerative colitis: beyond what meets the eye. Lancet Gastroenterol Hepatol 2022; 7: 2-4
- 3 Digby-Bell JL, Atreya R, Monteleone G. et al. Interrogating host immunity to predict treatment response in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2020; 17: 9-20
- 4 Ponsioen CY, de Groof EJ, Eshuis EJ. et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. Lancet Gastroenterol Hepatol 2017; 2: 785-792
- 5 Stevens TW, Haasnoot ML, D'Haens GR. et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: retrospective long-term follow-up of the LIR!C trial. Lancet Gastroenterol Hepatol 2020; 5: 900-907
- 6 Sandborn WJ, Feagan BG, D'Haens G. et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2021; 385: 1280-1291
- 7 Sandborn WJ, Peyrin-Biroulet L, Zhang J. et al. Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis. Gastroenterology 2020; 158: 550-561
- 8 Feagan BG, Danese S, Loftus Jr EV. et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet 2021; 397: 2372-2384
- 9 https://news.abbvie.com/news/press-releases/second-phase-3-induction-study-confirms-upadacitinib-rinvoq-improved-clinical-endoscopic-and-histologic-outcomes-in-ulcerative-colitis-patients.htm
- 10 https://news.abbvie.com/alert-topics/immunology/upadacitinib-rinvoq-meets-primary-and-all-ranked-secondary-endpoints-in-first-phase-3-induction-study-in-ulcerative-colitis.htm
- 11 https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-met-primary-and-all-secondary-endpoints-in-52-week-phase-3-maintenance-study-in-ulcerative-colitis-patients.htm
- 12 Abbvie. Upadacitinib (RINVOQ®) Achieved Primary and Key Secondary Endpoints in First Phase 3 Induction Study in Patients with Crohn's Disease. https://news.abbvie.com/news/press-releases/upadacitinib-rinvoq-achieved-primary-and-key-secondary-endpoints-in-first-phase-3-induction-study-in-patients-with-crohns-disease.htm . Stand: 10.02.2022
- 13 Sands BE, Chen J, Feagan BG. et al. Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study. Gastroenterology 2017; 153: 77-86.e6
- 14 Sandborn WJ, Ferrante M, Bhandari BR. et al. Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis. Gastroenterology 2020; 158: 537-549.e10
- 15 Sands BE, Peyrin-Biroulet L, Kierkus J. et al. Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease. Gastroenterology 2022; 162: 495-508
- 16 Sandborn WJ, D'Haens GR, Reinisch W. et al. GALAXI-1 Investigators. Guselkumab for the treatment of Crohn's disease: Induction results from the Phase 2 GALAXI-1 study.. Gastroenterology 2022;
- 17 Schreiber SW, Ferrante M, Panaccione R. et al. Risankizumab induces early clinical remission and response in patients with moderate-to-severe crohn’s disease: Results from the phase 3 advance and motivate studies. J Crohns Colitis 2021; 15 (Suppl. 01) S026-S027
- 18 Ferrante M, Liao Y, Pang Y. et al Efficacy and Safety of Risankizumab as Maintenance Therapy in Patients With Crohn's Disease: 52 Week Results From the Phase 3 FORTIFY Study. United Eur Gastroenterol J 2021; 9 (Suppl. 1)
- 19 Schmitt H, Billmeier U, Dieterich W. et al. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut 2019; 68: 814-828
- 20 Schmitt H, Ulmschneider J, Billmeier U. et al. The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis. J Crohns Colitis 2020; 14: 508-524
- 21 Atreya R, Peyrin-Biroulet L, Klymenko A. et al. Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial. Lancet Gastroenterol Hepatol 2020; 5: 1063-1075
- 22 Sands BE, Peyrin-Biroulet L, Loftus Jr EV. et al. VARSITY Study Group. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med 2019; 381 (13) 1215-1226
- 23 Sands BE, Irving PM, Hoops T. et al Ustekinumab versus adalimumab for induction and maintenance therapy in moderate-to-severe Crohn’s disease: the SEAVUE study.. Abstract presented at: Digestive Disease Week; May 21-23, 2021; Virtual Meeting
- 24 Atreya R, Neurath MF. Mechanisms of molecular resistance and predictors of response to biological therapy in inflammatory bowel disease. Lancet Gastroenterol Hepatol 2018; 3: 790-802