ASTHMA

Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma

D B Price¹, D Hernandez², P Magyar³, J Fiterman⁴, K M Beeh⁵, I G James⁶, S Konstantopoulos⁷, R Rojas⁸, J A van Noord⁹, M Pons¹⁰, L Gilles¹¹, J A Leff¹¹ for the Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group^*

¹ University of Aberdeen, Aberdeen, UK
² Hospital Civil de Guadalajara, Guadalajara, Mexico
³ Department of Pulmonology, Semmelweis University, Budapest, Hungary
⁴ Pucrs Medical School, Porto Alegre, Brazil
⁵ Pulmonary Division, University Hospital, Mainz, Germany
⁶ Spring House Surgery, Bolton, Lancashire, UK
⁷ Pneumonology Clinic, Medical School University Hospital of Ioannina, Greece
⁸ Tucuman National University, San Miguel de Tucumán, Argentina
⁹ Atrium Medical Center, Department of Pulmonology Heerlen, The Netherlands
¹⁰ Ospedale Civico, Lugano, Switzerland
¹¹ Merck and Co Inc, Whitehouse Station, New Jersey, USA

Correspondence to:
Correspondence to:
Professor D B Price, Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK;
d.price{at}abdn.ac.uk

Background: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.

Methods: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 µg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 µg/day (n=448) or budesonide 1600 µg/day (n=441) for 12 weeks.

Results: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1–3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" ß agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.

Conclusion: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.

Keywords: asthma; add-on therapy; leukotriene receptor antagonists; montelukast; budesonide

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