Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma

Abstract

Background: Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.

Methods: We reviewed patient choice to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma.

Results: Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR 3.10, 95% CI 1.68-5.73) and prior study medication changes (two or more changes: OR 2.77, 95% CI 1.51-5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR 0.54, 95% CI 0.32-0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR 29.28, 95% CI 16.07-53.36) when compared with those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice.

Conclusions: Belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for the generalisability of models of care in severe asthma and require further focused studies.

Trial registration: ClinicalTrials.gov NCT02717689.

Conflict of interest statement

Conflict of interest: J. Busby has nothing to disclose. Conflict of interest: J.G. Matthews has nothing to disclose. Conflict of interest: R. Chaudhuri reports grants, personal fees for advisory board work and nonfinancial support for meeting attendance from AstraZeneca, personal fees for advisory board work from GlaxoSmithKline and Novartis, personal fees for advisory board work and nonfinancial support for meeting attendance from Chiesi, nonfinancial support for meeting attendance from Napp Pharmaceuticals, outside the submitted work. Conflict of interest: I.D. Pavord reports personal fees for lectures, advisory board honoraria, sponsorship to attend scientific meetings, and payments for organising educational events from AstraZeneca, personal fees for lectures, advisory board honoraria, and sponsorship to attend scientific meetings from Boehringer Ingelheim and GlaxoSmithKline, personal fees for lectures from Aerocrine and Chiesi, personal fees for lectures and advisory board honoraria from Almirall and Novartis, advisory board honoraria from Genentech, Regeneron, Sanofi, Circassia and Knopp, personal fees for lectures, payments for organising educational events, and sponsorship to attend scientific meetings from Teva, grants from the National Institute for Health Research, outside the submitted work. Conflict of interest: T.C. Hardman has nothing to disclose. Conflict of interest: J.R. Arron has patents “Diagnosis and treatments relating to Th2 inhibition” (US 9,684,000 B2) and “Diagnosis and treatments relating to Th2 inhibition” (US 9,995,755 B2) issued with rights assigned to Genentech, a member of the Roche group, and is an employee of Genentech, Inc. and owns stocks/options in the Roche group. Conflict of interest: P. Bradding reports grants from Genentech, other (consultancy work on behalf of the University of Leicester) from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: C.E. Brightling reports grants and personal fees from GlaxoSmithKline, AstraZeneca, Sanofi, Novartis, Chiesi, Genentech, Gossamer, Mologic and 4D Pharma, all paid to the institution and outside the submitted work. Conflict of interest: D.F. Choy is an employee of Genentech, Inc. and owns stocks/options in the Roche group. Conflict of interest: D.C. Cowan has nothing to disclose. Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and Teva, consultation for Teva and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline; he is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin-out company. Conflict of interest: C.E. Hanratty has nothing to disclose. Conflict of interest: T.W. Harrison reports grants, personal fees and nonfinancial support from AstraZeneca, grants and personal fees from GlaxoSmithKline, personal fees from Vectura, Synairgen and Chiesi, outside the submitted work. Conflict of interest: C.T. Holweg is an employee and stock owner of Genentech Inc., a member of the Roche Group, outside the submitted work. Conflict of interest: P.H. Howarth reports employment by GlaxoSmithKline. Conflict of interest: S.J. Fowler reports personal fees for lectures and support to attend an international conference from AstraZeneca, grants and personal fees for lectures from Boehringer Ingelheim, personal fees for lectures, participation in an advisory board, and support to attend an national conference from Chiesi, personal fees for lectures from GlaxoSmithKline, Novartis and Teva, outside the submitted work. Conflict of interest: J.L. Lordan has nothing to disclose. Conflict of interest: A.H. Mansur reports personal and institution payment for talks, advisory board meetings, sponsorship to attend conferences and education grants for service developments from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi, Teva and others, outside the submitted work. Conflict of interest: A. Menzies-Gow reports grants and personal fees from AstraZeneca, personal fees from Novartis, GlaxoSmithKline, Sanofi and Vectura, personal fees and nonfinancial support from Teva and Boehringer Ingelheim, outside the submitted work. Conflict of interest: R.M. Niven has received lecture fees, advisory board activity and been supported to attend international meetings/conferences in the last 5 years by the following companies: AstraZeneca, Boehringer, Boston Scientific, Chiesi, Napp, Novartis and Teva. None of these have any relevance to the manuscript; R.M. Niven owns no shares or stocks and is not personally or in any family way connected to any pharmaceutical companies. Conflict of interest: D.S. Robinson has nothing to disclose. Conflict of interest: S.M. Walker has nothing to disclose. Conflict of interest: A. Woodcock reports personal fees for lectures from GlaxoSmithKline, personal fees for lectures and consultancy from Novartis, personal fees for consultancy from Chiesi, other (chairing research projects) from Reacta Biotech, Axalbion and Medicines Evaluation Unit, outside the submitted work. Conflict of interest: L.G. Heaney reports other (sponsorship for meeting attendance) from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Napp Pharmaceutical, personal fees for lectures and advisory board work from Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia, grants from Medimmune, Novartis UK, Roche/Genentech Inc., and GlaxoSmithKline, and is academic lead for the Medical Research Council Stratified Medicine UK Consortium in severe asthma, which involves industrial partnerships with Amgen, Genentech/Hoffman la Roche, AstraZeneca, Medimmune, GlaxoSmithKline, Aerocrine and Vitalograph, outside the submitted work.

Copyright ©The authors 2022.

Figures

FIGURE 1

Comparison of multivariate analysis for reduce, maintain and increase advisories. ER: emergency room; ACQ: Asthma Control Questionnaire; OCS: oral corticosteroid; ICS: inhaled corticosteroid; LAMA: long-acting muscarinic antagonist.

FIGURE 2

Exacerbation outcome in patients with dissociated symptoms and type 2 inflammation biomarkers. a) High symptoms/low type 2 inflammation biomarkers. We observed no benefit with increased corticosteroid dose. b) Low symptoms/high type 2 inflammation biomarkers. We observed substantial benefit with increased corticosteroid dose. HR: hazard ratio.