title: Combination therapy: the future of management for idiopathic pulmonary fibrosis?
abstract: Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons. Future clinical assessment will probably include add-on trials in which a new drug is combined with an intervention with established efficacy; this development is in turn likely to herald the use of combination regimens in clinical practice. Personalised medicine (the selection of monotherapies on the basis of individualised biomarker signal) is an intrinsically attractive alternative approach, but is unlikely to be useful in routine management of idiopathic pulmonary fibrosis in the medium-term future because of the complex nature of the disease's pathogenesis. In this Personal View, we review the pleiotropic nature of disease pathogenesis in idiopathic pulmonary disease, the use of combination regimens in other selected chronic lung diseases, and the conceptual basis for combination therapies in interstitial lung disorders other than idiopathic pulmonary fibrosis. On the basis of these considerations, and the emergence of data from add-on trials, we believe that the future of management for idiopathic pulmonary fibrosis lies in the development of combination regimens.
authors.affiliation: Department of Respiratory Medicine, Unit for Interstitial Lung Diseases, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.affiliation: Department of Thoracic Medicine and Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete, Crete, Greece.
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Antoniou
authors.affiliation: Inserm U1152, Université Paris Diderot, PRES Sorbonne Paris Cité, LabEx Inflamex, and Assistance Publique-Hôpitaux de Paris, DHU FIRE, Paris, France; Service de Pneumologie A, Centre de Compétence des Maladies Pulmonaires Rares, Hôpital Bichat, Paris, France.
authors.forename: Keren
authors.initials: K
authors.lastname: Borensztajn
authors.affiliation: Department of Pneumology/Allergology, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Hôpital Louis Pradel, Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: Inserm U1152, Université Paris Diderot, PRES Sorbonne Paris Cité, LabEx Inflamex, and Assistance Publique-Hôpitaux de Paris, DHU FIRE, Paris, France; Service de Pneumologie A, Centre de Compétence des Maladies Pulmonaires Rares, Hôpital Bichat, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.affiliation: Centre for Interstitial Lung Diseases and University Medical Center Utrecht, Department of Pulmonology, St. Antonius Hospital Nieuwegein, Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.affiliation: NIHR Biological Research Unit, Royal Brompton Hospital, Sydney Street, London, UK.
authors.forename: Toby M
authors.initials: TM
authors.lastname: Maher
authors.affiliation: Department of Diseases of the Thorax, Ospedale GB Morgagni, Forlì, Italy.
authors.forename: Venerino
authors.initials: V
authors.lastname: Poletti
authors.affiliation: National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Richeldi
authors.affiliation: Regional Centre for Interstitial and Rare Lung Diseases, Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vancheri
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK. Electronic address: athol.wells@rbht.nhs.uk.
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
mesh_terms: D001249:Asthma / Q000188:drug therapy; D004359:Drug Therapy, Combination; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy*; D057285:Precision Medicine; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy