TWICS results suggest no role for low-dose theophylline as add-on therapy in COPD
medwireNews: The addition of low-dose theophylline to inhaled corticosteroids (ICS) does not reduce the risk of exacerbations among patients with chronic obstructive pulmonary disease (COPD), findings from the TWICS trial indicate.
As reported in JAMA, ICS-treated COPD patients with a smoking history of more than 10 pack–years and at least two exacerbations treated with antibiotics, oral corticosteroids or both in the previous year were randomly assigned to receive 1 year of treatment with low-dose oral theophylline (200 mg once or twice daily depending on ideal bodyweight and current smoking status) or placebo.
Average rates of exacerbation over the treatment period were similar among the 772 participants in the theophylline group and their 764 counterparts given placebo, at 2.24 and 2.23 exacerbations per patient, respectively, giving a nonsignificant incidence rate ratio (IRR) of 0.99 after adjustment for factors such as age, sex and pack–years of smoking.
And a number of secondary outcomes, including mortality rates, episodes of pneumonia, COPD Assessment Test score and modified Medical Research Council dyspnoea score, were also comparable among patients treated with theophylline versus placebo, say David Price, from the University of Aberdeen in the UK, and fellow TWICS (Theophylline With Inhaled Corticosteroids) investigators.
However, they found that average rates of severe exacerbations requiring hospital admission were significantly lower among patients in the theophylline group, at 0.17 per patient versus 0.24 per patient in the placebo group (adjusted IRR=0.72).
The authors of an accompanying editorial, Gerard Criner (Temple University, Philadelphia, Pennsylvania, USA) and Bartolome Celli (Brigham and Women’s Hospital, Boston, Massachusetts, USA), say that this finding “may be attributable to a lack of correction for multiple statistical comparisons”.
Nonetheless, they note that “patients with a prior history of hospitalizations for COPD accounted for the majority of patients who had reduced hospitalizations while taking low-dose theophylline”, and the drug “may have benefited those with the greatest degree of physiological and functional impairment.” Therefore, further investigations “are needed in this particular patient subpopulation”, they add.
The investigators report that low-dose theophylline was not associated with increased rates of adverse reactions or serious adverse events (AEs). Serious cardiac AEs occurred in 2.4% of patients in the theophylline group and 3.4% of those in the placebo group, while serious gastrointestinal and neurological AEs occurred in a corresponding 2.7% versus 1.3% and 1.4% versus 0.9%, respectively.
Taken together, the TWICS results “do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations”, conclude Price and team.
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