Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma

Allergy, Asthma & Clinical Immunology

David I Bernstein⁷  Jacques Hébert²  Amarjit Cheema³  Kevin R Murphy⁶  Ivan Chérrez-Ojeda⁴  Carlos Eduardo Matiz-Bueno¹  Wen-Ling Kuo⁵  Hendrik Nolte⁵ 

[1] Fundación Salud Bosque, Bogota, Colombia

[2] Centre de Recherche Appliquée en Allergie de Québec, Québec, Canada

[3] Alpha Medical Research, Mississauga, Ontario, Canada

[4] RESPIRALAB Allergy, Respiratory & Sleep Center, Guayaquil, Ecuador

[5] Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ USA

[6] Boys Town National Research Hospital, Boys Town, Nebraska, USA

[7] Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

关键词: onset of action;    noninferiority;    fluticasone propionate/salmeterol;    mometasone furoate/formoterol;    asthma;   

Others  :  792557
DOI  :  10.1186/1710-1492-7-21

 received in 2011-07-08, accepted in 2011-12-07,  发布年份 2011

【 摘 要 】

Background

Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma.

Methods

Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 μg (delivered as 2 inhalations of MF-MDI 100 μg) twice daily (BID), subjects (aged ≥12 y) were randomized to MF/F-MDI 200/10 μg BID (delivered as 2 inhalations of MF/F-MDI 100/5 μg) or FP/S administered via a dry powder inhaler (DPI) 250/50 μg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV₁ AUC_{0-12 h}). Secondary assessments included onset of action (change from baseline in FEV₁ at 5 minutes postdose on day 1) and patient-reported outcomes.

Results

722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV₁ AUC_{0-12 h} change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV₁ at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]).

Conclusions

The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints.

Trial registration

ClinicalTrials.gov: NCT00424008

【 授权许可】

   
2011 Bernstein et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention. [http:/ / www.ginasthma.org/ guidelines-gina-report-global-strat egy-for-asthma.html] webcite Accessed November 15, 2011
• [2]National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report. [http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm] webcite Accessed December 14, 2010
• [3]Meltzer EO, Kuna P, Nolte H, S Nayak A, Laforce C, on Behalf of the P04073 Study Investigators: Mometasone Furoate/Formoterol Reduces Asthma Deteriorations and Improves Lung Function. Eur Rispirol J 2011, in press. http://erj.ersjournals.com/content/early/2011/08/04/09031936.00020310.long webcite. Accessed Sep 7, 2011
• [4]Nathan RA, Nolte H, Pearlman DS: Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids. Allergy Asthma Proc 2010, 31(4):269-279.
• [5]Weinstein SF, Corren J, Murphy K, Nolte H, White M: Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg and 400/10 microg combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids. Allergy Asthma Proc 2010, 31(4):280-289.
• [6]Maspero JF, Nolte H, Cherrez-Ojeda I: Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma. J Asthma 2010, 47(10):1106-1115.
• [7]Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR: Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999, 14(4):902-907.
• [8]Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK: Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 1992, 47(2):76-83.
• [9]Juniper EF, Guyatt GH, Willan A, Griffith LE: Determining a minimal important change in a disease-specific Quality of Life Questionnaire. J Clin Epidemiol 1994, 47(1):81-87.
• [10]Juniper EF, Svensson K, Mork AC, Stahl E: Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med 2005, 99(5):553-558.
• [11]Fish JE, Karpel JP, Craig TJ, Bensch GW, Noonan M, Webb DR, Silverman B, Schenkel EJ, Rooklin AR, Ramsdell JW, Nathan R, Leflein JG, Grossman J, Graft DF, Gower RG, Garay SM, Frigas E, Degraff AC, Bronsky EA, Bernstein DI, Berger W, Shneyer L, Nolop KB, Harrison JE: Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma. J Allergy Clin Immunol 2000, 106(5):852-860.
• [12]Kemp JP, Berkowitz RB, Miller SD, Murray JJ, Nolop K, Harrison JE: Mometasone furoate administered once daily is as effective as twice-daily administration for treatment of mild-to-moderate persistent asthma. J Allergy Clin Immunol 2000, 106(3):485-492.
• [13]Nathan RA, Nayak AS, Graft DF, Lawrence M, Picone FJ, Ahmed T, Wolfe J, Vanderwalker ML, Nolop KB, Harrison JE: Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate. Ann Allergy Asthma Immunol 2001, 86(2):203-210.
• [14]Nayak AS, Banov C, Corren J, Feinstein BK, Floreani A, Friedman BF, Goldsobel A, Gottschlich GM, Hannaway PJ, Lampl KL, Lapidus RJ, Lawrence M, Lumry W, Munk Z, Pearlman D, Scardella AT, Schenkel EJ, Segal AT, Segall N, Silverman B, Shneyer L, Nolop KB, Harrison JE: Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma. Ann Allergy Asthma Immunol 2000, 84(4):417-424.
• [15]Berger WE, Ford LB, Mahr T, Nathan RA, Crim C, Edwards L, Wightman DS, Lincourt WR, Rickard K: Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids. Ann Allergy Asthma Immunol 2002, 89(4):393-399.
• [16]Chuchalin A, Jacques L, Frith L: Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids. Clin Drug Investig 2008, 28(3):169-181.
• [17]Nelson HS, Busse WW, deBoisblanc BP, Berger WE, Noonan MJ, Webb DR, Wolford JP, Mahajan PS, Hamedani AG, Shah T, Harding SM: Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma. J Allergy Clin Immunol 1999, 103(2 Pt 1):267-275.
• [18]Chowdhury BA, Dal Pan G: The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med 2010, 362(13):1169-1171.
• [19]Walters EH, Gibson PG, Lasserson TJ, Walters JA: Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid. Cochrane Database Syst Rev 2007, (1):CD001385.
• [20]Cote C, Pearle JL, Sharafkhaneh A, Spangenthal S: Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: a multicenter, randomized study. Pulm Pharmacol Ther 2009, 22(1):44-49.
• [21]van Noord JA, Smeets JJ, Raaijmakers JA, Bommer AM, Maesen FP: Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. Eur Respir J 1996, 9(8):1684-1688.
• [22]Murphy KR, Bender BG: Treatment of moderate to severe asthma: patient perspectives on combination inhaler therapy and implications for adherence. J Asthma Allergy 2009, 2:63-72.
• [23]Juniper EF, Bousquet J, Abetz L, Bateman ED: Identifying 'well-controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. Respir Med 2006, 100(4):616-621.
• [24]Rachelefsky GS, Liao Y, Faruqi R: Impact of inhaled corticosteroid-induced oropharyngeal adverse events: results from a meta-analysis. Ann Allergy Asthma Immunol 2007, 98(3):225-238.