Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterised by progressive airflow limitation. It affects approximately 1 million people in the UK, is the fifth leading cause of death in the UK and costs the NHS approximately £1 billion annually. Exacerbations of COPD account for 60% of NHS COPD costs and are associated with accelerated rate of lung function decline, reduced physical activity, reduced quality of life, increased mortality and increased risk of comorbidities such as acute myocardial infarction and stroke. Current treatment includes inhaled corticosteroids (ICS), usually in combination with inhaled Long Acting Beta Agonist (LABA) to reduce exacerbation rates and improve lung function. However the COPD airway inflammation is relatively insensitive to the anti-inflammatory effects of ICS and even high doses fail to prevent exacerbations. It has been observed that the reduced HDAC2 activity of COPD can be reversed in a dose-dependent manner by theophylline at ‘low’ concentrations.
The TWICS trial, funded by the NIHR HTA programme, was a national, multi-centre randomised controlled trial which aimed to determine the clinical effectiveness and cost-effectiveness of adding low dose theophylline (Uniphyllin MR 200mg od or bd [depending on smoking status and ideal body weight]) to inhaled corticosteroid therapy in patients with COPD and a history of exacerbations.
1578 participants were recruited from 121 primary and secondary care sites across the UK (60% of participants from primary care). . Participants were randomised to low-dose theophylline or placebo for one year. The primary clinical outcome was the number of participant reported COPD exacerbations necessitating a change in management (minimum change treatment with antibiotics and/or oral corticosteroids) during the one year treatment period. For people with COPD at high risk of exacerbation, adding low-dose oral theophylline to a drug regimen that includes ICS confers no overall clinical or health economic benefit.
Contacts
- Seonaidh Cotton; s.c.cotton@abdn.ac.uk
Status
CompletedPublications
Trial protocol:
Devereux, G., Cotton, S., Barnes, P. et al. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial. Trials 16, 267 (2015).
https://doi.org/10.1186/s13063-015-0782-2
http://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-0782-2
Trial Results:
Devereux, G., Cotton, S., Fielding, S., McMeekin, N., Barnes, P. J., Briggs, A., Burns, G., Chaudhuri, R., Chrystyn, H., Davies, L., De Soyza, A., Gompertz, S., Haughney, J., Innes, K., Kaniewska, J., Lee, A., Morice, A., Norrie, J., Sullivan, A., Wilson, A., Price, D. Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial. JAMA, vol. 320, no. 15, pp. 1548-1559.
https://jamanetwork.com/journals/jama/fullarticle/2707459
Devereux, G., Cotton, S., Fielding, S., McMeekin, N., Barnes, P. J., Briggs, A., Burns, G., Chaudhuri, R., Chrystyn, H., Davies, L., Soyza, A. D., Gompertz, S., Haughney, J., Innes, K., Kaniewska, J., Lee, A., Morice, A., Norrie, J., Sullivan, A., Wilson, A., Price, D. Low-dose oral theophylline combined with inhaled corticosteroids for people with chronic obstructive pulmonary disease and high risk of exacerbations: a RCT. Health technology assessment (Winchester, England), vol. 23, no. 37, pp. 1-146
https://www.journalslibrary.nihr.ac.uk/hta/hta23370#/full-report