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Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: an interventional open-label study
  1. John Busby1,
  2. Cecile T J Holweg2,
  3. Akiko Chai2,
  4. Peter Bradding3,
  5. Fang Cai2,
  6. Rekha Chaudhuri4,5,
  7. Adel H Mansur6,
  8. James Laurence Lordan7,
  9. John G Matthews8,
  10. Andrew Menzies-Gow9,
  11. Robert Niven10,
  12. Tracy Staton2,
  13. Liam G Heaney11
  1. 1 Centre for Experimental Medicine, Queen's University Belfast School of Medicine Dentistry and Biomedical Sciences, Belfast, UK
  2. 2 Genentech Inc. (a member of the Roche Group), South San Francisco, California, USA
  3. 3 Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
  4. 4 Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK
  5. 5 Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, Scotland
  6. 6 Respiratory, Heartlands Hospital, Birmingham, UK
  7. 7 Respiratory, Freeman Hospital, Newcastle upon Tyne, UK
  8. 8 Product Development, Genentech Inc. (a member of the Roche Group), South San Francisco, California, USA
  9. 9 Royal Brompton Hospital, London, UK
  10. 10 Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  11. 11 Centre of Infection and Immunity, Queens University Belfast, Belfast, UK
  1. Correspondence to Professor Liam G Heaney, Centre for Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, UK; l.heaney{at}qub.ac.uk

Abstract

Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day prednisolone boost (0.5 mg/kg). High-dose OCS reduced median blood eosinophils (−60 cells/µl; 95% CI −140 to 10), periostin (−8.4 ng/mL; −11.6 to –2.8), FeNO (−19.0 ppb; −28.5 to –4.0), IL-5 (−0.17 pg/mL; −0.28 to –0.08) and IL-13 (−0.15 pg/mL; −0.27 to –0.03). There were small improvements in mean FEV1 (0.16 L; 0.05 to 0.27) and (Asthma Control Questionnaire) ACQ-7 score (0.3; 0.0 to 0.7). Study measures returned to baseline 1-month postintervention. Following rescue OCS, 1 month is sufficient before using type-2 biomarkers to guide long-term treatment.

Trial registration number NCT01948401.

  • asthma pharmacology
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Footnotes

  • Contributors JB conducted the statistical analysis and drafted the manuscript. CTJH, AC, FC, JGM, TS and LGH contributed to the planning and conduct of the clinical trial including assay development and interpretation of data and critical review of the study. PB, RC, AHM, JLL, AM-G and RN contributed to the planning and conduct of the clinical trial, interpretation of data and critical review of the study. All authors reviewed and approved the final version of the manuscript. JB acts as study guarantor.

  • Funding Data were generated and supplied by Genentech Inc. Funding for the analysis was supplied by the Medical Research Council (MR/M016579/1).

  • Competing interests CH, AC, JGM, TS are (or were at time of study) employees of Genentech Inc., a Member of the Roche Group and own Roche stock. RC has attended Advisory Board Meetings for AstraZeneca, GSK, Novartis and Teva and been a speaker at meetings for AstraZeneca. She has attended conferences supported by Boehringer, Teva, AstraZeneca and received educational grants from Novartis and Aerocrine. AHM received personal and department funds for talks and advisory board meetings and was sponsored to attend national and international conferences from pharmaceutical companies that include GlaxoSmithKline, Astra Zeneca, Novartis, NAPP, Boehringer Ingelheim, Roche, Chiesi. AM-G has attended advisory boards with GlaxoSmithKline, Novartis, AstraZeneca, Boehringer Ingelheim and Teva. He has received speaker fees from Novartis, AstraZeneca, Vectura, Boehringer Ingelheim, Sanofi and Teva. He has participated in research with Hoffman La Roche, GlaxoSmithKline, Boehringer Ingelheim and Astra Zeneca. He has attended international conferences with Teva and Boehringer Ingelheim and has consultancy agreements with AstraZeneca, Sanofi and Vectura. RN has received an unrestricted grant of £10,000 from Novartis in 2010 towards development of clinical services at the University Hospital of South Manchester. He has run preceptorship programmes in 2015 and 2016. These programmes have resulted in payment to the University Hospital of south Manchester for amounts not exceeding £10,000. He has also performed lecturing at Pharmaceutically sponsored meetings for the following pharmaceutical companies in the last 3 years: Astra Zeneca (<£1000), Boehringer Ingelheim (<£2000) Boston scientific (<£5000) Chiesi (<£1000), Novartis < £10,000, Napp (<£2000), Teva (<£2000). He has sat on advisory boards for the following companies in the last 3 years (Astra Zeneca, Boehringer Ingelheim, Boston scientific, Chiesi, GSK, Novartis Vectura and Teva), receiving reimbursement not exceeding £5000 per company. He has received sponsorship support to attend international academic meetings from Astra Zeneca, Boehringer ingelheim, Novartis, GSK, Chiesi and TEVA. RN (or any members of his family) has no shares or any pecuniary interest in any pharmaceutical industry and has no shareholdings or dividends and is not a paid consultant for any company. LGH is Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies.

  • Patient consent for publication Not required.

  • Ethics approval National Research Ethics Service East of England (Cambridge South Committee Ref: 13/EE/0099).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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