Oral Low-dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients With Severe COPD

Cosío, Borja G.; Shafiek, Hanaa; Iglesias, Amanda; Yáñez, Aina M.; Córdova, Rocío; Palou, Alexandre; Rodríguez-Roisín, Robert; Peces-Barba, Germán; Pascual, Sergi; Gea, Joaquim; Sibila, Oriol; Barnes, Peter J.; Agustí, Àlvar

doi:10.1016/j.chest.2016.04.011

Cited by 53 publications

(55 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 The few randomized clinical trials of low-dose theophylline have been small (58-110 participants), reported contradictory results, and have had major limitations. [30][31][32] The current pragmatic trial recruited 1578 participants with 98% ascertainment of the primary outcome. This high ascertainment rate was achieved by participants who ceased study medication attending scheduled study assessments, the request for exacerbation data from general practice staff, or the inspection of primary care records.…”

Section: Discussionmentioning

confidence: 99%

“…The exacerbation rate in this trial is somewhat higher than recent explanatory trials 33,34 ; however, it is consistent with the recent pragmatic UK Salford Lung Study, which used an inclusion criterion of at least 1 exacerbation and reported exacerbation rates of 1.74 to 1.90 per year. 35 Previous low-dose theophylline studies used a single dose for all participants 10,11,30 ; however, in the current study, theophylline dosing was personalized (determined by IBW and smoking status; designed to achieve plasma theophylline concentrations of 1 to 5 mg/L). The use of IBW avoided the potential for inappropriately high doses of theophylline in overweight participants.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD

Devereux

Cotton

Fielding

et al. 2018

JAMA

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. OBJECTIVE To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. DESIGN, SETTING, AND PARTICIPANTS The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. INTERVENTIONS Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). MAIN OUTCOMES AND MEASURES The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. RESULTS Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). CONCLUSIONS AND RELEVANCE Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD

Devereux

Cotton

Fielding

et al. 2018

JAMA

Self Cite

View full text Add to dashboard Cite

show abstract

“…Gegenüber Placebo zeigt Theophyllin eine leichte Besserung der Symptomatik [106], als Zusatztherapie zu Salmeterol eine Zunahme des FEV 1 und eine Abnahme der Atemnot [107] (Evidenz B). Eine Reduktion der Exazerbationsrate wurde in eine Studie bei COPD-Patienten berichtet [106], in einer anderen Analyse jedoch nicht bestätigt [108].…”

Section: Methylxanthineunclassified

Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD)

et al. 2018

View full text Add to dashboard Cite

This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.

show abstract

“…Despite that theophylline enhancing histone deacetylase (HDAC) activity and improving corticosteroid sensitivity were recognized (79). Oral low dose theophylline on top of ICS/LABA failed to reduce COPD exacerbation (80).…”

Section: Comparing Selective Pde4 Inhibitors With Xanthine Derivativesmentioning

confidence: 99%

Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases

Kawamatawong

2017

J. Thorac. Dis.

View full text Add to dashboard Cite

Oral Low-dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients With Severe COPD

Cited by 53 publications

References 24 publications

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD

Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD)

Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases

Contact Info

Product

Resources

About