Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD

Terzano, Claudio; Petroianni, Angelo; Conti, Vittoria; Ceccarelli, Daniela; Graziani, Elda; Sanduzzi, Alessandro; D'Avelli, Serena

doi:10.1016/j.rmed.2008.07.012

« Previous Next »Respiratory Medicine
Volume 102, Issue 12 , Pages 1701-1707, December 2008

Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD

Claudio Terzano
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy
Angelo Petroianni
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy
- Corresponding author. Tel.: +39 06 4074517; fax: +39 06 40800276.
Vittoria Conti
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy
Daniela Ceccarelli
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy
Elda Graziani
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy
Alessandro Sanduzzi
- Institute of Respiratory Diseases, II Faculty of Medicine, University of Naples, Italy
Serena D'Avelli
- Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, “Sapienza” University of Rome, Via Casal de' Pazzi, 16, 00156 Rome, Italy

Received 22 January 2008; accepted 14 July 2008. published online 29 August 2008.

Summary

Aim

To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24h in patients with moderate to severe COPD.

Methods

In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18μg once-daily (8am); Tr2: TIO 18μg (8am)+FOR 12μg (8pm); Tr3: FOR 12μg twice-daily (8am and 8pm); Tr4: TIO 18μg (8am)+FOR 12μg twice-daily (8am and 8pm); Tr5: FOR 12μg twice-daily (8am and 8pm)+TIO 18μg (8pm). Spirometries were performed during 24h (13 steps) on Day1 and Day30. End-points were: gain of FEV₁ (ΔFEV₁) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol.

Results

Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8mL and +119.1mL; Day30 +160.2mL, and +160.5mL, respectively). Daily means of ΔFEV₁ were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80puffs/die) and Tr5 (0.71puffs/die).

Conclusions

In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV₁ during the 24h (CV=0.256). These results are relevant for opening new ways in clinical practice.

Keywords: COPD Therapy, Tiotropium, Formoterol, Spirometry