Abstract
Background: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICS).
Objective: To determine the effectiveness of stepping up to high-dose ICS.
Methods: A historic cohort study of asthma patients (≥13 years old), identified from two large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICS were compared to those who stepped up from medium- to high-dose ICS, while patients who stepped up from low- to medium-dose were compared to those who stepped up from low- to high-dose ICS. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and number of exacerbations and antibiotics courses were analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.
Results: The mean follow-up time to first exacerbation was 2.7 (SD 2.7) years for those who remained on stable medium-dose ICS and 2.0 (SD 2.2) years for those who stepped up from medium-to high117 dose ICS. A similar pattern was noted for those who stepped-up from low- to medium-ICS dose (2.6 (SD 2.5) years) and from low- to high-dose ICS (2.3 (SD 2.5) years). Patients who stepped up from medium- to high-dose ICS (n=6,879) had a higher risk of exacerbations during follow-up compared to those who remained on medium-dose ICS (n=51,737; hazard ratio [HR] 1.17, 95% confidence interval 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n=3,232) compared to low to medium-dose (n=12,659) ICS (HR 1.10 [1.04-1.17]). A step-up to high-dose ICS was also associated with higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts (BEC).
Conclusion: We found no evidence that a step-up to high-dose ICS is effective in preventing future asthma exacerbations.
Objective: To determine the effectiveness of stepping up to high-dose ICS.
Methods: A historic cohort study of asthma patients (≥13 years old), identified from two large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICS were compared to those who stepped up from medium- to high-dose ICS, while patients who stepped up from low- to medium-dose were compared to those who stepped up from low- to high-dose ICS. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and number of exacerbations and antibiotics courses were analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.
Results: The mean follow-up time to first exacerbation was 2.7 (SD 2.7) years for those who remained on stable medium-dose ICS and 2.0 (SD 2.2) years for those who stepped up from medium-to high117 dose ICS. A similar pattern was noted for those who stepped-up from low- to medium-ICS dose (2.6 (SD 2.5) years) and from low- to high-dose ICS (2.3 (SD 2.5) years). Patients who stepped up from medium- to high-dose ICS (n=6,879) had a higher risk of exacerbations during follow-up compared to those who remained on medium-dose ICS (n=51,737; hazard ratio [HR] 1.17, 95% confidence interval 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n=3,232) compared to low to medium-dose (n=12,659) ICS (HR 1.10 [1.04-1.17]). A step-up to high-dose ICS was also associated with higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts (BEC).
Conclusion: We found no evidence that a step-up to high-dose ICS is effective in preventing future asthma exacerbations.
| Original language | English |
|---|---|
| Pages (from-to) | 532-543 |
| Number of pages | 12 |
| Journal | The Journal of Allergy and Clinical Immunology: In Practice |
| Volume | 11 |
| Issue number | 2 |
| Early online date | 9 Nov 2022 |
| DOIs | |
| Publication status | Published - Feb 2023 |
Bibliographical note
Funding: The OPCRD is established and maintained by Optimum Patient Care (OPC) Ltd. This study was funded by AstraZeneca and conducted collaboratively with the OPRI Pte Ltd.Acknowledgments
The authors wish to acknowledge the input of Dr Marjan Kerkhof and Dr Jaco Voorham for their contributions to the study. We would like to acknowledge Dr Julia Granerod (PhD) of the Observational and Pragmatic Research Institute (OPRI), Singapore, for her medical writing support, and Ms. Shilpa Suresh (MSc) of the Observational and Pragmatic Research Institute (OPRI), Singapore, for editorial and formatting assistance that supported the development of this publication.
Data Availability Statement
The data set supporting the conclusions of this article was derived from the CPRD (www.cprd.com) and the OPCRD (www.opcrd.co.uk). The CPRD has broad National Research Ethics Service Committee ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymized research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency Committee, the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee for the CPRD. The authors do not have permission to give public access to the study data set; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd.com. Access to OCPRD can be made via the OCPRD website (https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk.Keywords
- asthma
- exacerbations
- corticosteroids
- high dose
- step-up