Vedolizumab in der Behandlung der Colitis ulcerosa und des Morbus Crohn – ein Konsensus der Arbeitsgruppe „Chronisch Entzündliche Darmerkrankungen“ der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie

Einleitung

Colitis ulcerosa und Morbus Crohn sind die beiden Hauptformen chronisch entzündlicher Darmerkrankungen (CED) [1] [2]. Sie sind durch abdominelle Schmerzen, Diarrhoen, die im Falle der Colitis ulcerosa häufig blutig sind, und Müdigkeit sowie einen oft chronisch-relapsierenden Verlauf gekennzeichnet. Intestinale Komplikationen wie Stenosen, Fisteln, Abszesse und das Auftreten von kolorektalen Karzinomen können Operationen erforderlich machen.

Das Therapieziel ist die kortisonfreie Remission [3] [4]. Aufgrund ihrer prognostischen Aussagekraft erlangt auch die mukosale Heilung zunehmende Bedeutung [5] [6]. Die gängigen Therapien reichen von Mesalazin, über Glukokortikoide, Immunsuppressiva (z. B. Azathioprin, 6-Mercaptopurin, Methotrexat) bis hin zu Tumornekrosefaktor-(TNF)-α-Antikörpern [3] [4] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]. Ein Teil der Patienten spricht jedoch auch auf die Therapie mit TNF-α-Antikörpern nicht an, hat trotz primären Ansprechens einen sekundären Wirkungsverlust oder entwickelt Nebenwirkungen, die ein Absetzen der Therapie erforderlich machen [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]. Ein Versagen auf eine Therapie mit einem TNF-α-Antikörper verringert die Ansprechrate auf einen zweiten Vertreter dieser Medikamentengruppe, sodass nicht nur der Bedarf für weitere wirksame Medikamente im Allgemeinen, sondern auch mit einem anderen Wirkmechanismus im Speziellen gegeben ist [8] [17].

Vedolizumab ist ein humanisierter monoklonaler IgG1-Antikörper, der spezifisch an das α₄β₇-Integrin bindet und dadurch ein neues und darmselektives Wirkprinzip besitzt. Vedolizumab ist seit Mai 2014 in der Europäischen Union für die Behandlung von erwachsenen Patienten mit mittelschwerer bis schwerer Colitis ulcerosa und mittelschwerem bis schwerem Morbus Crohn zugelassen, die entweder auf konventionelle Therapie oder einen der TNF-α-Antikörper unzureichend angesprochen haben, nicht mehr darauf ansprechen oder eine Unverträglichkeit gegen eine entsprechende Therapie aufweisen [18] [19]. Die empfohlene Dosierung beträgt unabhängig vom Körpergewicht 300 mg i. v., die zu Woche 0, 2 und 6 und danach alle 8 Wochen verabreicht werden.

Der vorliegende Konsensusbericht der Arbeitsgruppe „Chronisch Entzündliche Darmerkrankungen“ der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) soll ein praktischer Leitfaden für den Einsatz von Vedolizumab bei Patienten mit einer CED sein und entstand in ähnlicher Art wie frühere Konsensusstatements dieser Arbeitsgruppe [20] [21]. Die Teilnehmer des Konsensus, die auch die Autoren dieses Berichts sind, wurden von GN ausgesucht und erarbeiteten Entwürfe für Text und Empfehlungen zu den von GN vorgeschlagenen Themen (Delphi-Prozess). Alle Konsensusteilnehmer sind Mitglieder der Arbeitsgruppe „Chronisch Entzündliche Darmerkrankungen“ der ÖGGH und haben langjährige Erfahrung in der Behandlung von ambulanten und stationären Patienten mit CED. Empfehlungen und Text basieren auf der verfügbaren Literatur (systematische Literatursuche mittels MedLine/PubMed und Cochrane Database sowie Abstracts der großen internationalen Kongresse) und wurden hinsichtlich Evidenzgrad (Level of Evidence, EL) und Empfehlungsgrad (Grade of Recommendation, RG) entsprechend dem Oxford Centre for Evidence Based Medicine bewertet ([Tab. 1]). Die Statements wurden im Rahmen eines Treffens am 21.1.2015 von den Konsensusteilnehmern erarbeitet und am 18.4.2015 im Rahmen des jährlich stattfindenden Treffens der Arbeitsgruppe „Chronisch Entzündliche Darmerkrankungen“ in Weyregg (Österreich) der ÖGGH vor einer größeren Teilnehmerzahl präsentiert, diskutiert und zur Abstimmung gebracht. Ein Statement galt als angenommen, wenn es eine Zustimmung von mindestens 80 % erhielt. Die Kapitel des Konsensusberichts wurden von den jeweiligen Teilnehmern verfasst, von allen anderen Autoren überarbeitet, und die finale Version wurde von allen akzeptiert.

Tab. 1 Evidenz- und Empfehlungsgrade basierend auf dem Oxford Centre for Evidence Based Medicine. (Quelle: „The Oxford 2011 Levels of Evidence“. http://www.cebm.net/index.aspx?o = 5653).

Level of Evidence (Treatment Benefits)
1[1]	Systematic review of randomized trials or n-of-1 trials
21	Randomized trial or observational study with dramatic effect
31	Non-randomized controlled cohort/follow-up study[2]
41	Case-series, case-control studies, or historically controlled studies2
51	Mechanism-based reasoning
Level of Evidence (Treatment Harms)
11	Systematic review of randomized trials, systematic review of nested case-control studies, n-of-1 trial with the patient you are raising the question about, or observational study with dramatic effect
21	Individual randomized trial or (exceptionally) observational study with dramatic effect
31	Non-randomized controlled cohort/follow-up study (postmarketing surveillance) provided there are sufficient numbers to rule out a common harm. (For long-term harms the duration of follow-up must be sufficient.)2
41	Case-series, case-control, or historically controlled studies2
51	Mechanism-based reasoning
Grades of Recommendation
A	Consistent level 1 studies
B	Consistent level 2 or 3 studies or extrapolation from level 1 studies
C	Level 4 studies or extrapolation from level 2 or 3 studies
D	Level 5 evidence or troublingly inconsistent or inconclusive studies of any level

¹ Level may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO [Patient, Intervention, Comparison, Outcome]), because of inconsistency between studies, or because the absolute effect size is very small; Levels may be graded up if there is a large or very large effect size.

² As always, a systematic review is generally better than an individual study.

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