Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma

Jorge F Maspero, Hendrik Nolte, Iván Chérrez-Ojeda, P04139 Study Group, Enrique Casal, Hector Defranchi, Carlos G Di Bartolo, Alberto L Dolmann, Jose E Jares, Jorge F Maspero, Luisa B Rey, Ahahi Yanez, Carlos Bisbal, Susana Munoz, Tamara Soler, Eduardo Castro, Ivan Cherrez, Rene Cordova, Efrén Guerrero, Victor Chur, Edgar Contreras, Jeremias Guerra, Gerardo Martinez, Jesus J Moran-Ochoa, Chavira M Perez, Marco Camere, William Chavez, Octavio Cubas, Felix Efrain, Andres Pineiro, Danilo Salazar, Jorge F Maspero, Hendrik Nolte, Iván Chérrez-Ojeda, P04139 Study Group, Enrique Casal, Hector Defranchi, Carlos G Di Bartolo, Alberto L Dolmann, Jose E Jares, Jorge F Maspero, Luisa B Rey, Ahahi Yanez, Carlos Bisbal, Susana Munoz, Tamara Soler, Eduardo Castro, Ivan Cherrez, Rene Cordova, Efrén Guerrero, Victor Chur, Edgar Contreras, Jeremias Guerra, Gerardo Martinez, Jesus J Moran-Ochoa, Chavira M Perez, Marco Camere, William Chavez, Octavio Cubas, Felix Efrain, Andres Pineiro, Danilo Salazar

Abstract

Objective: The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.

Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.

Results: The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.

Conclusions: One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma.

Figures

Figure 1
Figure 1
Patient disposition. ICS, inhaled corticosteroid; FP/S, fluticasone propionate/salmeterol combination; MF/F, mometasone furoate/formoterol. ‘Patient population used for safety analyses. tPatient population used for efficacy analyses, identified before database lock.
Figure 2
Figure 2
Mean plasma cortisol 24-hour AUC at baseline, week 26, and week 52. Patients who had both 0- and 24-hour measurements were included in the analysis. AUC, area under the curve; FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol. *p < .043 versus baseline within treatment groups.
Figure 3
Figure 3
Improvement in mean 24-hour total asthma symptom scores. Total asthma symptom scores are the sum of wheezing, coughing, and difficulty breathing scores, based on a scale of 0 (none) to 3 (severe). FP/S, fluticasone propionate/salmeterol; MF/F, mometasone furoate/formoterol.

References

    1. Murphy KR. Asthma: versatile treatment for a variable disease. J Asthma. 2005;42:149–157.
    1. Bernstein DI. ABCs of asthma. Clin Cornerstone. 2008;8:9–25.
    1. Dougherty RH, Fahy JV. Acute exacerbations of asthma: epidemiology, biology and the exacerbation-prone phenotype. Clin Exp Allergy. 2009;39:193–202.
    1. Fanta CH. Asthma. N Engl J Med. 2009;360:1002–1014.
    1. Global Initiative for Asthma. Global strategy for asthma manage ment and prevention. Available at: . Accessed July 29, 2010.
    1. National Heart Lung and Blood Institute - National Asthma Education and Prevention Program. Expert panel report 3: guide lines for the diagnosis and management of asthma. Available at: . Accessed July 29, 2010.
    1. Tan RA, Corren J. Mometasone furoate in the management of asthma: a review. Ther Clin Risk Manag. 2008;4:1201–1208.
    1. Bernstein DI, Berkowitz RB, Chervinsky P, Dvorin DJ, Finn AF, Gross GN, Karetzky M, Kemp JP, Laforce C, Lumry W, Mendelson LM, Nelson H, Pearlman D, Rachelefsky G, Ratner P, Repsher L, Segal AT, Selner JC, Settipane GA, Wanderer A, Cuss FM, Nolop KB, Harrison JE. Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler. Respir Med. 1999;93:603–612.
    1. 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;106:852–860.
    1. 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;106:485–492.
    1. 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;84:417–424.
    1. 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;86:203–210.
    1. D'Urzo A, Karpel JP, Busse WW, Boulet LP, Monahan ME, Lutsky B, Staudinger H. Efficacy and safety of mometasone furoate admin istered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids. Curr Med Res Opin. 2005;21:1281–1289.
    1. Bensch GW, Prenner B, Berkowitz R, Galant S, Ramsdell J, Lutsky B. Once-daily evening administration of mometasone furoate in asthma treatment initiation. Ann Allergy Asthma Immunol. 2006;96:533–540.
    1. Karpel JP, Nayak A, Lumry W, Craig TJ, Kerwin E, Fish JE, Lutsky B. Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma. Respir Med. 2007;101:628–637.
    1. Bensch G, Lapidus RJ, Levine BE, Lumry W, Yegen U, Kiselev P, Della Cioppa G. A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. Ann Allergy Asthma Immunol. 2001;86:19–27.
    1. Pleskow W, LaForce CF, Yegen U, Matos D, Della Cioppa G. Formoterol delivered via the dry powder Aerolizer inhaler versus albuterol MDI and placebo in mild-to-moderate asthma: a randomized, double-blind, double-dummy trial. J Asthma. 2003;40:505–514.
    1. LaForce C, Prenner BM, Andriano K, Lavecchia C, Yegen U. Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma. J Asthma. 2005;42:101–106.
    1. Dahl R, Creemers JP, Van Noord J, Sips A, Della Cioppa G, Thomson M, Andriano K, Kottakis J, Fashola T. Comparable efficacy and tolerability of formoterol (Foradil) administered via a novel multi-dose dry powder inhaler (Certihaler) or the Aerolizer dry powder inhaler in patients with persistent asthma. Respiration. 2004;71:126–133.
    1. Reynolds NA, Lyseng-Williamson KA, Wiseman LR. Inhaled salmeterol/fluticasone propionate: a review of its use in asthma. Drugs. 2005;65:1715–1734.
    1. Lasserson TJ, Cates CJ, Ferrara G, Casali L. Combination fluticasone and salmeterol versus fixed dose combination budesonide and for moterol for chronic asthma in adults and children. Cochrane Database Syst Rev. 2008 CD004106.
    1. Chylack LT, Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, Friend J, McCarthy D, Wu SY. The lens opacities classifi cation system III. The longitudinal study of cataract study group. Arch Ophthalmol. 1993;111:831–836.
    1. Derendorf H, Nave R, Drollmann A, Cerasoli F, Wurst W. Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. Eur Respir J. 2006;28:1042–1050.
    1. Morice AH, Hochmuth L, Ekelund J, Thorén A, Puterman AS. Comparable long-term safety and efficacy of a novel budesonide/formoterol pressurized metered-dose inhaler versus budesonide/formoterol Turbuhaler in adolescents and adults with asthma. Pulm Pharmacol Ther. 2008;21:32–39.
    1. Peters SP, Prenner BM, Mezzanotte WS, Martin P, O'Brien CD. Long-term safety and asthma control with budesonide/formoterol ver sus budesonide pressurized metered-dose inhaler in asthma patients. Allergy Asthma Proc. 2008;29:499–516.
    1. Nathan RA, Nolte H, Pearlman DS. Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 μg combina tion treatment in patients with persistent asthma previously receiv ing medium-dose inhaled corticosteroids. Allergy Asthma Proc. 2010;31:269–279.
    1. Weinstein S, Corren J, Murphy K, Nolte H, White M. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 μg and 400/10 μg combination treatments in patients with per sistent asthma previously receiving high-dose inhaled corticosteroids. Allergy Asthma Proc. 2010;31:280–289.
    1. Barnes NC. The properties of inhaled corticosteroids: similarities and differences. Prim Care Respir J. 2007;16:149–154.
    1. Meltzer EO, Wenzel S. The efficacy and safety of mometasone furoate delivered via a dry powder inhaler for the treatment of asthma. J Asthma. 2006;43:765–772.
    1. Broadley KJ. Beta-adrenoceptor responses of the airways: for better or worse? Eur J Pharmacol. 2006;533:15–27.
    1. Rodrigo GJ, Moral VP, Marcos LG, Castro-Rodriguez JA. Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review. Pulm Pharmacol Ther. 2009;22:9–19.
    1. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid ther apy: a systematic review and meta-analysis. Arch Intern Med. 1999;159:941–955.
    1. Allen DB. Effects of inhaled steroids on growth, bone metabolism, and adrenal function. Adv Pediatr. 2006;53:101–110.
    1. D'Urzo A. Mometasone furoate dry-powder inhaler for the control of persistent asthma. Expert Opin Pharmacother. 2007;8:2871–2884.
    1. Karpel JP, Nelson H. Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma. Curr Med Res Opin. 2007;23:2897–2911.
    1. Chylack LT, Jr, Gross GN, Pedinoff A. A randomized, controlled trial to investigate the effect of ciclesonide and beclomethasone dipropionate on eye lens opacity. J Asthma. 2008;45:893–902.
    1. Bisgaard H, Allen D, Milanowski J, Kalev I, Willits L, Davies P. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1–3 years with recurrent wheezing. Pediatrics. 2004;113:e87–e94.
    1. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJH, Pauwels RA, Pedersen SE. Can guideline-defined asthma control be achieved? The gaining optimal asthma control study. Am J Respir Crit Care Med. 2004;170:836–844.
    1. Pauwels RA, Lofdahl C, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med. 1997;337:1405–1411.
    1. 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;362:1169–1171.

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