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Effect of theophylline as adjunct to inhaled corticosteroids on exacerbations in patients with COPD

Graham Devereux, Seonaidh Cotton, Shona Fielding, et al.
JAMA 2018;320:1548–59

Chronic obstructive pulmonary disease (COPD) remains a growing global health concern, with exacerbations being associated with high morbidity and mortality. Research continues to explore novel, optimal therapeutic options for COPD patients to aid the improvement of COPD management and outcomes. Theophylline has long been used to treat COPD; however, high blood concentrations have been related to adverse effects. Recent data has highlighted a potential role for low-dose theophylline in combination with inhaled corticosteroids (ICS), demonstrating up to a 10,000-fold increase in the anti-inflammatory effects of ICS therapy. Despite this, the evidence to support the clinical relevance of low-dose theophylline has not been fully established.

In this double-blind, placebo-controlled, randomised study, researchers aimed to investigate the clinical effectiveness of low-dose theophylline in combination with ICS therapy in patients with COPD and frequent exacerbations. The clinical trial recruited 1578 participants across 121 UK primary and secondary care sites, all of which had COPD with a forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio of >0.7 and at least two exacerbations in the previous year. Patients were randomised into two groups: treatment (n=791) group, who received low-dose theophylline (200 mg) either once or twice a day for 1 year, or placebo (n=787) group.

Results demonstrated that the addition of low-dose theophylline to ICS therapy did not significantly decrease the number of recorded exacerbations (moderate to severe) in adults with COPD. A total number of 1727 exacerbations were recorded in the theophylline group, with 1703 exacerbations being recorded in the placebo group. Based on these findings, the researchers concluded that low-dose theophylline as an adjunctive therapy to ICS was not clinically effective in the prevention of COPD exacerbations.

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