ERJ Open Research (2018-10-01)

Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study

  • Vincent Cottin,
  • Dirk Koschel,
  • Andreas Günther,
  • Carlo Albera,
  • Arata Azuma,
  • C. Magnus Sköld,
  • Sara Tomassetti,
  • Philip Hormel,
  • John L. Stauffer,
  • Indiana Strombom,
  • Klaus-Uwe Kirchgaessler,
  • Toby M. Maher,
  • PASSPORT study group,
  • Peter Cerkl,
  • Holger Flick,
  • Christian Geltner,
  • Judith Löffler-Ragg,
  • Michael Studnicka,
  • Elisabeth Bendstrup,
  • Helle Dall Madsen,
  • Saher B. Shaker,
  • Maritta Kilpelainen,
  • Marjukka Myllaerniemi,
  • Minna Purokivi,
  • Seppo Saarelainen,
  • Emmanuel Bergot,
  • Philippe Bonniaud,
  • Raphael Borie,
  • Pascal Chanez,
  • Vincent Cottin,
  • Francis Couturaud,
  • Claire Dromer,
  • Frederic Gagnadoux,
  • Anne-Sophie Gamez,
  • Anne Gondouin,
  • Dominique Israel-Biet,
  • Stephane Jouneau,
  • Romain Kessler,
  • Francois Lebargy,
  • Sylvain Marchand-Adam,
  • Borsi Melloni,
  • Jean-Marc Naccache,
  • Christophe Pison,
  • Gregoire Prevot,
  • Martine Reynaud-Gaubert,
  • Abdellatif Tazi,
  • Dominique Valeyre,
  • Benoit Wallaert,
  • Jost Achenbach,
  • Stefan Andreas,
  • Burkhard Bewig,
  • Reiner Bonnet,
  • Stephan Budweiser,
  • Ulrich Costabel,
  • Martin Faehling,
  • Joachim Ficker,
  • Juergen Fisher,
  • Sven Glaeser,
  • Christian Grah,
  • Christian Grohe,
  • Andreas Günther,
  • Martin Hetzel,
  • Wolfgang Hohenforst-Schmidt,
  • David Jungck,
  • Peter Kardos,
  • Claus Keller,
  • Martin Kohlhaeufl,
  • Dirk Koschel,
  • Claus Kroegel,
  • Rainer Kruegel,
  • Berthold Michels,
  • Joachim Mueller-Quernheim,
  • Claus Neurohr,
  • Heinz-Theodor Pelzer,
  • Michael Pfeifer,
  • Michael Prediger,
  • Klaus F. Rabe,
  • Winifried Randerath,
  • Nicolas Scheonfeld,
  • Robert Scheubel,
  • Jens Schreiber,
  • Hartwig Schutte,
  • Bernd Schoenhofer,
  • Barbara Wagener,
  • Tobias Welte,
  • Michael Westhoff,
  • Heinrike Wilkens,
  • Hubert Wirtz,
  • Michael Henry,
  • Michael Keane,
  • Anthony O'Regan,
  • Katherine O'Reilly,
  • Carlo Albera,
  • Fabrizio Luppi,
  • Sandra Nutini,
  • Alberto Pesci,
  • Venerino Poletti,
  • Elisabetta Rosi,
  • Paola Rottoli,
  • Thomas Eagan,
  • Durdica Kulosman,
  • Tone Blorg Sjaheim,
  • Karl Axel Karlsson,
  • Magnus Sköld,
  • Sanjay Agrawal,
  • Kesavan Suresh Babu,
  • Stephen Bianchi,
  • Nazia Chaudhuri,
  • Sophie Fletcher,
  • Michael Gibbons,
  • Simon Hart,
  • Gisli Jenkins,
  • Toby Maher,
  • Ann Millar,
  • Joanna Porter,
  • Nicky Simler,
  • Lisa Spencer,
  • Monica Spiteri,
  • Melissa Wickremasinghe

DOI
https://doi.org/10.1183/23120541.00084-2018
Journal volume & issue
Vol. 4, no. 4

Abstract

Read online

Real-world studies include a broader patient population for a longer duration than randomised controlled trials (RCTs) and can provide relevant insights for clinical practice. PASSPORT was a multicentre, prospective, post-authorisation study of patients who were newly prescribed pirfenidone and followed for 2 years after initiating treatment. Physicians collected data on adverse drug reactions (ADRs), serious ADRs (SADRs) and ADRs of special interest (ADRSI) at baseline and then every 3 months. Post hoc stepwise logistic regression models were used to identify baseline characteristics associated with discontinuing treatment due to an ADR. Patients (n=1009, 99.7% with idiopathic pulmonary fibrosis) had a median pirfenidone exposure of 442.0 days. Overall, 741 (73.4%) patients experienced ADRs, most commonly nausea (20.6%) and fatigue (18.5%). ADRs led to treatment discontinuation in 290 (28.7%) patients after a median of 99.5 days. Overall, 55 (5.5%) patients experienced SADRs, with a fatal outcome in six patients. ADRSI were reported in 693 patients, most commonly gastrointestinal symptoms (38.3%) and photosensitivity reactions/skin rashes (29.0%). Older age and female sex were associated with early treatment discontinuation due to an ADR. Findings were consistent with the known safety profile of pirfenidone, based on RCT data and other post-marketing experience, with no new safety signals observed.