Chronic obstructive pulmonary disease: add-on theophylline offers no benefit

  • Devereux G & al.
  • Health Technol Assess
  • 1 Jul 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.


  • The addition of low-dose oral theophylline to inhaled corticosteroids (ICSs) does not offer overall clinical or health economic benefits in patients with chronic obstructive pulmonary disease (COPD) at high risk for exacerbation.

Why this matters

  • Despite advances in the current National Institute for Health and Care Excellence COPD guidelines, there is still an unmet need for improved pharmacological treatment of COPD, particularly prevention of exacerbations.

Study design

  • For intention-to-treat (IIT) analysis, 1536 participants recruited in the Theophylline With Inhaled CorticoSteroid (TWICS) trial were randomly assigned (1:1) to receive either low-dose theophylline (n=772) or placebo (n=764) for 1 year.
  • Primary outcome: number of participant-reported exacerbations during the 1-year treatment period that required treatment with antibiotics and/or oral corticosteroids.
  • Funding: Health Technology Assessment programme of the National Institute for Health Research.

Key results

  • No significant difference was observed in the number of exacerbations between theophylline vs placebo groups (adjusted incidence rate ratio [aIRR], 0.99; 95% CI, 0.91-1.08; P=.840).
  • Exacerbations requiring hospital treatment were less frequent in theophylline vs placebo group (aIRR, 0.72; 95% CI, 0.55-0.94; P=.017).
  • Theophylline vs placebo group did not differ in:
    • non-COPD-related hospital admissions (P=.952),
    • episodes of pneumonia (P=.307),
    • Forced expiratory volume1% (P=.555),
    • COPD assessment test score (P=.975),
    • modified Medical Research Council dyspnoea scale (P=.074),
    • total mortality (P=.369) or COPD-/respiratory-related mortality (P=.762), and
    • any (P=.116) or serious (P=.616) adverse events.


  • The proportion of participants who ceased trial medication was higher than anticipated.