German Guideline for Idiopathic Pulmonary Fibrosis – Update on Pharmacological Therapies 2017

Jürgen Behr; Andreas Günther; Francesco Bonella; Klaus Geißler; Dirk Koschel; Michael Kreuter; Antje Prasse; Nicolas Schönfeld; Helmut Sitter; Joachim Müller-Quernheim; Ulrich Costabel

doi:10.1055/s-0043-123035

Pneumologie, Table of Contents

Pneumologie 2018; 72(02): 155-168
DOI: 10.1055/s-0043-123035

Guideline

German Guideline for Idiopathic Pulmonary Fibrosis – Update on Pharmacological Therapies 2017

S2k-Leitlinie Idiopathische Lungenfibrose – Update zur medikamentösen Therapie 2017

Jürgen Behr

¹Medizinische Klinik und Poliklinik V, Klinikum der Universität München (LMU) und Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center, Mitglied des Deutschen Zentrums für Lungenforschung

,

Andreas Günther

²Schwerpunkt Fibrosierende Lungenerkrankungen, Universitätsklinikum Gießen – Marburg, Standort Gießen, Justus-Liebig-Universität Gießen, sowie Agaplesion Pneumologische Klinik Waldhof-Elgershausen, University of Giessen Marburg Lung Center, Mitglied des Deutschen Zentrums für Lungenforschung

,

Francesco Bonella

³Schwerpunkt interstitielle und seltene Lungenkrankheiten, Ruhrlandklinik, Universitätsklinikum Essen

,

Klaus Geißler

⁴Patientenvertretung Lungenfibrose e.V., Essen

,

Dirk Koschel

⁵Abteilung Innere Medizin/Pneumologie, Fachkrankenhaus Coswig, Zentrum für Pneumologie, Allergologie, Beatmungsmedizin, Thoraxchirurgie

,

Michael Kreuter

⁶Zentrum für interstitielle und seltene Lungenerkrankungen, Pneumologie und Beatmungsmedizin, Thoraxklinik, Universitätsklinikum Heidelberg, Mitglied des Deutschen Zentrums für Lungenforschung

,

Antje Prasse

⁷Klinik für Pneumologie, Medizinische Hochschule Hannover und Clinical Research Center Fraunhofer Institut ITEM, Mitglied des Deutschen Zentrums für Lungenforschung

,

Nicolas Schönfeld

⁸Klinik für Pneumologie, Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Berlin

,

Helmut Sitter

⁹Institut für Theoretische Chirurgie, Philipps-Universität Marburg

,

Joachim Müller-Quernheim

¹⁰Klinik für Pneumologie, Department Innere Medizin, Medizinische Fakultät, Albert Ludwigs Universität, Freiburg

,

Ulrich Costabel

³Schwerpunkt interstitielle und seltene Lungenkrankheiten, Ruhrlandklinik, Universitätsklinikum Essen

› Author Affiliations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 – 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan. A less clear but still negative recommendation (B, 1-b) was attributed to the treatment of IPF with the phosphodiesterase-5-inhibitor sildenafil and acetyl-cysteine monotherapy. In contrast to the international guideline antacid therapy as a general treatment for IPF was rated negative, based on conflicting results of recent analyses (recommendation C; evidence 4). An unanimous positive recommendation was granted for the antifibrotic drugs nintedanib and pirfenidone for the treatment of IPF (A, 1-a). For some open questions in the management of IPF patients for which firm evidence is lacking the guideline also offers recommendations based on expert consensus.

Zusammenfassung

Die idiopathische Lungenfibrose (idiopathische pulmonale Fibrose, IPF) ist eine schwerwiegende Lungenerkrankung, die häufig innerhalb von zwei bis vier Jahren nach Diagnosestellung zum Tod führt. Seit Veröffentlichung der deutschen IPF-Leitlinie im Jahr 2013 liegen neue Therapiestudien vor, die eine Neubewertung der Behandlungsstrategien erfordern. Abweichend von der Vorgängerleitlinie wurde in der aktuellen Überarbeitung nicht mehr das GRADE-System sondern die Oxford Evidenzsystematik mit drei Empfehlungsgraden (A, B, C) verwendet, weil dieses System eine differenziertere Betrachtung erlaubt. Folgende Medikamente wurden mit dem Empfehlungsgrad A und dem Evidenzgrad 1-b als nicht geeignet für die Behandlung der IPF klassifiziert: Triple-Therapie aus Prednisolon, Azathioprin und Acetylcystein; Antikoagulation mit Vitamin-K-Antagonisten; Imatinib; Ambrisentan; Bosentan; Macitentan. Weniger eindeutig ist die negative Bewertung des Phosphodiesterase-5-Inhibitors Sildenafil und der Acetylcystein-Monotherapie (Empfehlungsgrad B, Evidenzgrad 2-b). Eindeutig positiv fiel die Empfehlung für Nintedanib und Pirfenidon zur Behandlung von IPF-Patienten aus (Empfehlungsgrad A, Evidenzgrad 1-a). Mit Empfehlungsgrad C und Evidenzgrad 4 wurde der generelle Einsatz von Antazida zur Behandlung der IPF als nicht zu empfehlen bewertet, da die Datenlage widersprüchlich ist; hier weicht die deutsche Leitlinie auch am deutlichsten von der internationalen Leitlinie ab. Am Ende der Leitlinie wird aus Expertensicht zu offenen Fragen in der Therapie der IPF Stellung genommen, für die bisher keine ausreichende Evidenzbasis existiert.

Full Text

References

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