Effects of Inhaled Mometasone Furoate on Growth Velocity and Adrenal Function: A Placebo-Controlled Trial in Children 4–9 Years Old with Mild Persistent Asthma

Abstract

Objective. To assess the effects of long-term mometasone furoate delivered via a dry powder inhaler (MF-DPI) on growth velocity and hypothalamic–pituitary–adrenal axis function in children with asthma. Study design. Children aged 4–9 years with asthma (n = 187) were randomized to MF-DPI 100 μg (delivered dose; actuated dose is 110 μg) once daily in the morning (QD AM), 100 μg twice daily (BID), 200 μg QD AM, or placebo for 52 weeks followed by a 3-month follow-up period. The primary outcome was growth velocity calculated from stadiometric heights recorded at each visit. Secondary outcomes included serum and 12-h urinary cortisol, serum osteocalcin, and urinary N-telopeptide. Results. MF-DPI 100 μg QD AM treatment did not significantly affect growth velocity compared with placebo (–0.10 ± 0.31 cm/y, p = 0.76). When the effect of a total daily dose of 200 μg MF-DPI on growth velocity was examined, no significant effect was demonstrated for MF-DPI 100 μg BID compared with placebo (–0.64 ± 0.39 cm/y, p = 0.10), although the change in mean growth velocity with MF-DPI 200 μg QD AM reached statistical significance (–0.70 ± 0.29 cm/y, p = 0.02). The effects of all examined doses of MF-DPI on mean plasma cortisol levels were similar to cortisol changes seen in the placebo group, suggesting an absence of drug-related effects. No differences in 12-h urinary cortisol or other outcomes were observed between groups. Conclusions. One year of treatment with a total daily dose of 100 μg of MF-DPI in the morning resulted in no significant difference, whereas a total daily dose of 200 μg of MF-DPI was associated with some changes in growth velocity when compared with placebo. The differences in growth velocity, and the absence of drug-related cortisol effects, support the use of a total daily dose of 100 μg of MF-DPI in children aged 4–9 years with mild persistent asthma.

• height
• hypothalamic–pituitary–adrenal axis
• inhaled corticosteroid
• mometasone furoate
• pediatric

Acknowledgments

The authors thank all the investigators and personnel for study C97–384 at these sites: Howard E. Beede, M.D., ICSL-Clinical Studies, Normal, IL; Thomas Bell, M.D., Montana Medical Research, LLC, Missoula, MT; David Bernstein, M.D., Bernstein Clinical Research, Cincinnati, OH; Mark H. Ellis, M.D., CHOC Pediatric Subspecialty Faculty, Division of Allergy, Asthma, and Immunology, Orange, CA; Stanley P. Galant, M.D., Clinical Trials of Orange County, Orange, CA; Pinkus Goldberg, M.D., Clinical Research Center of Indiana, Indianapolis, IN; David Gossage, M.D., Allergy, Asthma and Sinus Center, Knoxville, TN; Leon S. Greos, M.D., Colorado Allergy and Asthma Center PC, Wheat Ridge, CO; Robert E. Grubbe, M.D., Allergy and Asthma Center, LLC, Oxford, AL; Anne-Marie Irani, M.D., Virginia Commonwealth University Medical College of VA, Richmond, VA; Harold B. Kaiser, M.D., Clinical Research Institute, Minneapolis, MN; Daniel Laszlo, M.D., Aspen Medical Center, Loveland, CO; Michael Lawrence, M.D., Center for Clinical Research, Taunton, MA; Allen K. Lieberman, M.D., HealthQuest Research, Austin, TX; Eli O. Meltzer, M.D., Allergy and Asthma Medical Group and Research Center, San Diego, CA; Henry Milgrom, M.D., National Jewish Medical and Research Center, Denver, CO; S. David Miller, M.D., New England Clinical Studies, North Dartmouth, MA; Anjuli S. Nayak, M.D., ICSL-Clinical Studies, Normal, IL; Michael Noonan, M.D., Allergy Associates Research Center, Portland, OR; Amit I. Patel, M.D., Integrated Research Group, Corona, CA; Patrick V. Perin, M.D., Advanced Asthma Allergy, Teaneck, NJ; Paul H. Ratner, M.D., Sylvania Research, San Antonio, TX; Anthony R. Rooklin, M.D., Asthma & Allergy Research Associates, Upland, PA; Michael E. Ruff, M.D., Pharmaceutical Research and Consulting, Inc., Dallas, TX; Eric J. Schenkel, M.D., Valley Clinical Research Center, Easton, PA; Robert H. Schwartz, M.D., AAIR Research Center, Rochester, NY; Gail G. Shapiro, M.D., ASTHMA, Inc., Seattle, WA; David P. Skoner, M.D., Children’s Hospital of Pittsburgh, Pittsburgh, PA; G. Edward Stewart II, M.D., Allergy & Asthma Care of Florida, Ocala, FL; and Mark L. Vandewalker, M.D., Clinical Research of the Ozarks, Inc., Rolla, MO.

Disclosures. This study was supported by Merck & Co, Inc. Dr. Skoner has received grant/research support from and/or has served as a consultant and/or speaker for AstraZeneca, GlaxoSmithKline, Merck & Co., Inc., Novartis Pharmaceuticals Corp., and Teva Respiratory, LLC. Dr. Meltzer has received grant/research support from and/or has served as an advisory board member, consultant, and/or speaker for Alcon, Alexza Pharmaceuticals, Amgen, Antigen Labs, Apotex, Astellas, AstraZeneca, Boehringer Ingelheim, Capnia, Dainippon Sumitomo Pharma, Dey, GlaxoSmithKline, ISTA, Johnson & Johnson, Kalypsys, MAP, MEDA, Merck & Co., Inc., National Jewish Health, Novartis, Procter & Gamble, Rady Children’s Hospital San Diego, Sandoz, sanofi-aventis, Schering-Plough, Sepracor, SRxA, Teva, UCB, VentiRx, Wockhardt, and Wyeth. Dr. Milgrom has received grant/research support from and/or has served as a speaker and/or advisor for AstraZeneca, Genentech, GlaxoSmithKline, Merck & Co., Inc., Novartis, Sepracor, and sanofi-aventis. Drs. Stryszak, Teper, and Staudinger are employees of Merck Research Laboratories. Medical writing and editorial assistance were provided by Erin P. Scott, Ph.D., of Complete Publication Solutions, LLC, Horsham, PA. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ.

Role of Funding Source. Merck & Co., Inc. was involved in the study design, as well as in the analysis and interpretation of the data. The authors made the final decision to submit the article.