Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy

Abstract

Background

Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.

Methods

Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.

Results

Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).

Conclusion

Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Keywords:

• severe asthma
• biologics
• real-world
• treatment pattern
• patient characteristics

Ethics Approval

This study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance Code of Conduct (EMA 2014; EUPAS33582) and with all applicable local and international laws and regulation. Registration of the ISAR database with the European Union Electronic Register of Post-Authorization studies was also undertaken (ENCEPP/DSPP/23720). ISAR has ethical approval from the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218). Governance was provided by The Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (registration number: ADEPT0420). All data collection sites in the International Severe Asthma Registry (ISAR) have obtained regulatory agreement in compliance with specific data transfer laws, country-specific legislation, and relevant ethical boards and organizations.

Acknowledgments

The authors would like to acknowledge Dr. James Zangrilli and Dr. Alex de Giorgio-Miller for their instrumental contributions to the study concept, Mr. Joash Tan (BSc, Hons) of the Observational and Pragmatic Research Institute (OPRI), for editorial and formatting assistance that supported the development of this publication.

The authors also thank the investigators and participating sites in ISAR for making this research possible.

ISAR Participating Sites:

• Argentina

  • Fundacion CIDEA

  • Fernandez Hospital Buenos Aires

  • Investigaciones en Patologias Respiratorias

• Australia

  • Austin Hospital, VIC

  • Campbelltown Hospital, NSW

  • Concord Hospital, NSW

  • Fiona Stanley Hospital, WA

  • Flinders Medical Centre, SA

  • Frankston Hospital, VIC

  • John Hunter Hospital, NSW

  • Monash Health, VIC

  • Princess Alexandra Hospital, QLD

  • Royal Adelaide Hospital, SA

  • Royal Prince Alfred Hospital, NSW

  • St George Specialist Centre, NSW

  • St Vincent Clinic, NSW

  • The Alfred Hospital, VIC

  • The Prince Charles Hospital, QLD

  • Western Health, Footscray, VIC

  • Woolcock Institute of Medical Research, NSW

• Bulgaria

  • Cvetanka Odjakova, Varna

  • Darina Dimova, Plovdiv

  • Diana Hristova, Sofia

  • Eleonora Stamenova, Sofia

  • Katya Noleva, Pazardzhik

  • Violina Vasileva, Dupnica

• Canada

  • University of British Columbia- Vancouver Coastal Health

  • University of British Columbia- Providence Health Care

  • University of Alberta

  • Toronto Western Hospital

  • University Institute of Cardiology and Respirology of Quebec

• Colombia

  • Fundacion Neumologica Colombiana, Bogotá

  • Institituto Neumológico del Oriente, Bucaramanga

  • Hospital Universitario San Ignacio, Bogotá

• Denmark

  • Bispebjerg University Hospital

  • Aarhus University Hospital

  • Gentofte University Hospital

  • Hvidovre University Hospital

  • Naestved University Hospital

  • Odense University Hospital

  • Roskilde University Hospital

  • Vejle Hospital

• Greece

  • Attikon University Hospital, Chaidari

  • University Hospital of Ioannina, Ioánnina

• India

  • Fortis Hospital, Kolkatta

  • West Bengal, D. Y. Patil hospital, Navi Mumbai, Maharashtra

• Ireland

  • Royal College of Surgeons

• Italy

  • Personalized Medicine, Asthma & Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI

  • UOC Allergology Department, Piacenza

  • Department of Experimental and Clinical Biomedical Sciences ”Mario Serio”, Respiratory Unit, Careggi University Hospital, Florence

  • Departmental Unit of Allergology and Pneumology, Hospital Institute Fondazione Poliambulanza, Brescia

  • Department of Internal Medicine, Clinical Immunology, Clinical Pathology and Infectious Diseases, Azienda Ospedaliera Universitaria Federico II, Naples

  • Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin

  • Department of Clinical and Biomedical Sciences, University of Milan, Respiratory Diseases, Sacco University Hospital, ASST Fatebenefratelli-Sacco, Milan

  • Pneumology Unit, Santa Maria Nuova Hospital, Azienda USL di Reggio Emilia IRCCS

  • Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan

  • Division of Respiratory Diseases, Department of Promoting Health, Maternal-Infant. Excellence and Internal and Specialized Medicine (Promise) G. D’Alessandro, University of Palermo, Palermo

  • Allergy and Clinical Immunology Unit, Department of Medicine, ”Carlo Poma” Hospital, Mantova

  • Respiratory Medicine, Department of Medical Sciences, University of Turin

  • Respiratory Unit and Adult Cystic Fibrosis Center, And Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, University of Milan

  • Department of Medicine and Surgery, University of Parma

  • Division of Allergy and Clinical Immunology, University of Salerno, Fisciano

  • Respiratory Department, Division of Respiratory Diseases ”Federico II” University, AO Dei Colli, Naples

  • Allergy and Clinical Immunology, University of Turin & AO Mauriziano, Turin

  • Division of Pneumology and Allergology, Policlinico, University of Catania

  • Allergy Unit, Fondazione Policlinico A. Gemelli, IRCCS, Rome

  • Department of Medicine, Allergy Unit Asthma Center, University of Verona

  • Department of Translational Medical Sciences, University of Campania ”L. Vanvitelli”, Naples

  • Department of Clinical and Experimental Sciences, University of Brescia, Spedali Civili, Brescia

  • Department of Emergency and Organ Transplantation, School and Chair of Allergology and Clinical Immunology, University of Bari Aldo Moro, Bari

  • Fondazione Policlinico Universitario A. Gemelli, IRCCS Catholic University of Rome

  • Department of Pharmacology, Faculty of Medicine Catholic, University of the Sacred Heart Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome

  • Division of Respiratory Diseases, IRCCS Policlinico San Matteo, Foundation and Department of Internal Medicine and Therapeutics, University of Pavia

  • University of Insubria, ICS Maugeri, IRCCS, Varese

  • Section of Respiratory Diseases, Medical and Surgical Sciences Department, University of Foggia

  • Department of Medical and Surgical Sciences, Section of Respiratory Diseases, University Magna Graecia, Catanzaro

  • Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa

• Japan

  • Hiroshima Allergy and Respiratory Clinic

  • Kindai University Hospital

  • Idaimae Minamiyojo Clinic

  • National Mie Hospital

  • Kobe University Hospital

  • Kyoto University Hospital

  • Mie University Hospital

  • Sagamihara National Hospital

  • Kochi Medical School Hospital

  • Nagoya City University Hospital

  • Dokkyo Medical University Hospital

  • Iwasaki Clinic

  • Kinki Hokuriku Airway disease Conference

• Kuwait

  • Kuwait University, Faculty of Medicine

  • Al-Rashed Allergy center, Ministry of Health, Kuwait

  • The Kuwait Foundation for the Advancement of Sciences

• Mexico

  • Hospital Médica Sur, Mexico City

  • Centro de Atención de Enfermedades Cardiopulmonares, Guadalajara

  • ISSSTE Hospital Regional Lic. Adolfo López Mateos, Mexico City

• South Korea

  • Seoul St. Mary’s Hospital

  • Konkuk University Hospital

  • Yeouido St. Mary’s Hospital

  • Ulsan University Hospital

  • Haeundae Paik Hospital

  • Hallym University Chuncheon Sacred Heart Hospital

  • Hanyang University Hospital

  • Hallym University Kangdong Sacred Heart Hospital

• Saudi Arabia

  • King Fahad Medical City, Riyadh

  • King Abdul Aziz University, Jeddah

• Spain

  • Hospital Lucus Augusti. Lugo. EOXI Lugo, Cervo e Monforte

  • Hospital Universitario Son Espases, Palma de Mallorca

  • Hospital Universitario de Cruces. Barakaldo, Bizkaia

  • Hospital Sta Creu i Sant Pau. Barcelona

  • University Hospital San Agustín. Avilés

  • Hospital Bellvitge. Barcelona

  • Hospital 12 de Octubre. Madrid

• Taiwan

  • Taipei Veterans General Hospital

  • Taipei Medical University, Shuang Ho Hospital

  • China Medical University Hospital

  • Kaohsiung Medical University Hospital

• United Arab Emirates

  • Rashid Hospital, Dubai

• UK

  • Belfast Health & Social Care Trust

  • Royal Brompton and Harefield Hospitals, London

  • Guy’s and St Thomas’ NHS Foundation Trust

  • Barts Health NHS Trust

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. The study was supervised by David B. Price.

Disclosure

Mohsen Sadatsafavi has received honoraria from AZ, BI, and GSK for purposes unrelated to the content of this manuscript and has received research funding from AZ and BI directly into his research account from AZ for unrelated projects.

Trung N. Tran is an employee of AstraZeneca. AstraZeneca is a co-funder of the International Severe Asthma Registry.

Nigel Chong Boon Wong reports grants from Optimum Patient Care Global, grants from AstraZeneca Ltd, during the conduct of the study.

Nasloon Ali was an employee of Observational and Pragmatic Research Institute (OPRI) at the time this research was conducted. OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca.

Con Ariti is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca.

Esther Garcia Gil was an employee of AstraZeneca at the time this research was conducted. AstraZeneca is a co-funder of the International Severe Asthma Registry.

Anthony Newell was an employee of Optimum Patient Care (OPC) at the time this research was conducted. OPC is a co-funder of the International Severe Asthma Registry.

Marianna Alacqua was an employee of AstraZeneca at the time this research was conducted. AstraZeneca is a co-funder of the International Severe Asthma Registry.

Mona Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline.

Alan Altraja has received lecture fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MSD, Norameda, Novartis, Orion, Sanofi, and Zentiva; personal fees from Teva, Shire Pharmaceuticals and CSL Behring, sponsorships from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MSD, Norameda, Sanofi, and Novartis; and has been a member of advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi, and Teva.

Riyad Al-Lehebi has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi, reports personal fees from Novartis and participated in advisory board fees from GlaxoSmithKline.

Mohit Bhutani: has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Pfizer, Sanofi Genzyme, Covis pharmaceuticals; has been an investigator on clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Sanofi Genzyme, Boehringer Ingelheim

Leif Bjermer has (in the last three years) received lecture or advisory board fees from Alk-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Sanofi, Genzyme/Regeneron, and Teva.

Anne-Sofie Bjerrum has received lecture fees from Astra Zeneca, GlaxoSmithKline, Novartis.

Arnaud Bourdin has received industry-sponsored grants from AstraZeneca-MedImmune, Boehringer-Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, Sanofi-Regeneron and consultancies with AstraZeneca-MedImmune, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, and Chiesi.

Lakmini Bulathsinhala is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca.

Anna von Bülow reports speakers fees and consultancy fees from AstraZeneca, GSK and Novartis, outside the submitted work. She has also attended advisory board for Novartis and AstraZeneca.

John Busby reports personal fees from NuvoAir, outside the submitted work.

Giorgio Walter Canonica has received research grants, as well as lecture or advisory board fees from A. Menarini, Alk-Albello, Allergy Therapeutics, Anallergo, AstraZeneca, MedImmune, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, Danone, Faes, Genentech, Guidotti Malesci, GlaxoSmithKline, Hal Allergy, Merck, MSD, Mundipharma, Novartis, Orion, Sanofi Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva, Thermo Fisher, and Valeas.

Victoria Carter is an employee of Optimum Patient Care, a co-funder of the International Severe Asthma Registry and reports grants from Optimum Patient Care Global, during the conduct of the study

Borja G. Cosio declares grants from Chiesi, AstraZeneca, Menarini, Teva and GSK; personal fees for advisory board activities from Chiesi, GSK, Novartis, Sanofi, Menarini, Teva and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, GSK, Menarini, Sanofi, Teva and AstraZeneca, outside the submitted work.

Richard W. Costello has received honoraria for lectures from Aerogen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Teva. He is a member of advisory boards for GlaxoSmithKline and Novartis, has received grant support from GlaxoSmithKline and Aerogen, has received personal fees from Respirasense, personal fees from PfizerBioNTech, during the conduct of the study and has patents in the use of acoustics in the diagnosis of lung disease, assessment of adherence and prediction of exacerbations, issued to 212.

J. Mark FitzGerald reports grants from AstraZeneca, GSK, Sanofi Regeneron, Novartis paid directly to UBC. Personal fees for lectures and attending advisory boards: AstraZeneca, GSK, Sanofi Regeneron, TEVA.

João A Fonseca reports grants from or research agreements with AstraZeneca, Mundipharma, Sanofi Regeneron and Novartis. Personal fees for lectures and attending advisory boards: AstraZeneca, GSK, Mundipharma, Novartis, Sanofi Regeneron and TEVA.

Liam G. Heaney declares he has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Circassia, Evelo Biosciences, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance and Teva; he has taken part in asthma clinical trials sponsored by Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen.

Enrico Heffler participates in speaking activities and industry advisory committees for AstraZeneca, Sanofi-Genzyme, GSK, Novartis, Regeneron, Stallergenes-Greer, TEVA, Circassia and Nestlè Purina, grants from AstraZeneca and GSK

Mark Hew declares grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Seqirus, for unrelated projects.

Flavia Hoyte declares honoraria from AstraZeneca. She has been an investigator on clinical trials sponsored by GlaxoSmithKline, Genentech, Teva, Sanofi and National Institute of Allergy and Infectious Diseases (NIAID), for which her institution has received funding.

Takashi Iwanaga declares grants from Astellas, Boehringer Ingelheim, Daiichi-Sankyo, Kyorin, MeijiSeika Pharma, Teijin Pharma, Ono, and Taiho, and lecture fees from Kyorin, GlaxoSmithKline, Sanofi and AstraZeneca.

David J. Jackson has received advisory board and speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva, Napp, Chiesi, Sanofi Regeneron, Novartis and research grant funding from AstraZeneca.

Rupert C. Jones declares grants from Astra Zeneca, Glaxo Smith Kline, Novartis OPRI and Teva and personal fees for consultancy, speakers’ fees or travel support from Astra Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Novartis and OPRI.

Mariko Siyue Koh reports grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Sanofi and Boehringer Ingelheim, outside the submitted work.

Piotr Kuna reports personal fees from Adamed, personal fees from AstraZeneca, personal fees from Berlin Chemie Manarini, personal fees from Boehringer Ingelheim, personal fees from Lekam, personal fees from Novartis, personal fees from Chiesi, personal fees from Polpharma, personal fees from Sanofi, personal fees from Teva, personal fees from Zentiva, personal fees from FAES, personal fees from Glenmark, outside the submitted work

Désirée Larenas Linnemann reports speaker or personal fees from ALK, Alakos, Armstrong, AstraZeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, Gossamer, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Purina institute, Sanofi, Siegfried, UCB, Carnot, Viatris, and grants from Sanofi, AbbVie, ALK, AstraZeneca, Circassia, Chiesi, GSK, Lilly, Novartis, Pfizer, Purina Institute and UCB, outside the submitted work

Sverre Lehmann declares receipt of lecture (personal) and advisory board (to employer) fees from AstraZeneca, Boehringer Ingelheim, and Novartis.

Lauri A. Lehtimäki declares personal fees for consultancy, lectures and attending advisory boards from ALK, AstraZeneca, Boehringer Ingelheim, Circassia, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Orion Pharma, Sanofi, and Teva.

Juntao Lyu is an employee of Optimum Patient Care (OPC). OPC is a co-funder of the International Severe Asthma Registry.

Jorge Maspero reports grants and personal fees from AstraZeneca, Sanofi, Novartis, and GSK, personal fees from IMMUNOTEK, personal fees from SANOFI, outside the submitted work.

Andrew N. Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva, andhas received speaker fees from AstraZeneca, Novartis, Teva and Sanofi. He has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva. He has had consultancy agreements with AstraZeneca and Sanofi.

Nikolaos G. Papadopoulos declares research support from Gerolymatos, Menarini, Nutricia, and Vian; and consultancy/speaker fees from ASIT, AZ, Boehringer Ingelheim, GSK, HAL Allergy, Medscape, Menarini, MSD, Mylan, Novartis, and Nutricia, OM Pharma, Sanofi, and Takeda, grant from Capricare.

Andriana I. Papaioannou has received fees and honoraria from Menarini, GSK, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi.

Luis Perez-de-Llano declares non-financial support, personal fees, and grants from Teva, Sanofi and AstraZeneca, Chesi; non-financial support and personal fees from Boehringer Ingelheim, Esteve, GlaxoSmithKline, Mundipharma, and Novartis; personal fees from MSD, TECHDOW PHARMA, Leo-Pharma, GEBRO and GILEAD; non-financial support from Menairi, grants, non-financial support from FAES during the conduct of the study.

Diahn-Warng Perng (Steve) received sponsorship to attend or speak at international meetings, honoraria for lecturing or attending advisory boards, and research grants from the following companies: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Daiichi Sankyo, Shionogi and Orient Pharma

Matthew Peters declares personal fees and non-financial support from AstraZeneca and GlaxoSmithKline.

Paul E. Pfeffer has attended advisory boards for AstraZeneca, Sanofi and GSK; has given lectures at meetings supported by AstraZeneca and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Sanofi and Novartis, for which his institution received remuneration; non-financial support from Chiesi; and has a current research grant funded by GlaxoSmithKline.

Celeste M. Porsbjerg has attended advisory boards for AstraZeneca, Novartis, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme.

Todor A. Popov declares relevant research support from Novartis and Chiesi Pharma.

Chin Kook Rhee declares consultancy and lecture fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mundipharma, MSD, Novartis, Sandoz, Sanofi, Takeda, and Teva-Handok.

Sundeep Salvi declares research support and speaker fees from Cipla, Glenmark, GSK

Camille Taillé has received lecture or advisory board fees and grants to her institution from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi and Novartis, for unrelated projects.

Carlos A. Torres-Duque has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis; has taken part in clinical trials from AstraZeneca, Novartis and Sanofi-Aventis; has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Grifols and Novartis.

Charlotte S. Ulrik has attended advisory boards for AstraZeneca, ALK-Abello, GSK, Boehringer-Ingelheim, Novartis, Chiesi, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Sandoz, Mundipharma, Chiesi, Boehringer-Ingelheim, Orion Pharma, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, Merck, InsMed, ALK-Abello, Sanofi-Genzyme, GlaxoSmithKline, Boehringer-Ingelheim, Regeneron, Chiesi and Novartis; and has received educational and research grants from AstraZeneca, MundiPharma, Boehringer-Ingelheim, Novartis, TEVA, GlaxoSmithKline and Sanofi-Genzyme; has received personal fees from Pfizer.

Seung Won Ra has received lecture fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis.

Eileen Wang has received honoraria from AstraZeneca, GlaxoSmithKline, Wefight, and Clinical Care Options. She has been an investigator on clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Novartis, Teva, and Sanofi, for which her institution has received funding. She has received personal fees from Wefight.

Michael E. Wechsler reports receiving consulting honoraria from AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Novartis, Regeneron, Sanofi and Teva; personal fees from Amgen, Avalo, Cerecor, Cytoreason, Eli Lilly, Equillium, Incyte, Kinaset, Phylaxis, Pulmatrix, Rapt and Sound Biologics.

David B. Price has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.