The Efficacy and Tolerability of Intravenous Montelukast in Acute Asthma Exacerbations in Japanese Patients

Abstract

Objectives. In Japan, the Asthma Prevention and Management Guidelines recommend nebulized β-agonists, IV (intravenous) drip corticosteroids, as well as IV drip aminophylline for acute asthma treatment. However, current treatment for acute asthma provides inadequate benefit for some patients. We evaluated the efficacy and safety of IV montelukast added to standard therapy in Japanese patients with acute asthma exacerbations. Methods. This multicenter, randomized, double-blind, parallel-group study compared IV montelukast 7 mg, 14 mg, and placebo in Japanese patients with acute asthma exacerbations (N = 242). Fifteen- to sixty-five-year-old patients with acute asthma were treated with standard care during a screening period that lasted ≤60 minutes. Patients with FEV₁ (forced expiratory volume in 1 second) ≤70 predicted were randomly allocated to one of three treatment groups. The primary end point was the time-weighted average change in FEV₁ from baseline over 60 minutes [ΔFEV₁ (0–60 minutes)] after study drug administration. Secondary end points included the time-weighted average change in FEV₁ over 20, 40, and 120 minutes [ΔFEV₁ (0–T min)]. Results. IV montelukast 7 mg was significantly more effective than placebo for the time-weighted average ΔFEV₁ (0–60 minutes) [least squares (LS) mean 0.09 L vs. 0.01 L; p < .05]. IV montelukast 14 mg was also more effective than placebo (LS mean 0.17 L; p < .001). Similar improvements in time-weighted average [ΔFEV₁ (0–T min)] were seen at all time points (all p < .05). Both doses of IV montelukast demonstrated a significant increase in average ΔFEV₁ compared with placebo within 10 minutes of administration (p < .001 to p < .01). The tolerability of IV montelukast was similar to that of placebo. Conclusion. IV montelukast was significantly more effective than placebo in the improvement of ΔFEV₁ in Japanese patients, suggesting its role as an adjunctive therapy to existing guideline recommendations.

• acute asthma
• aminophylline
• asthma exacerbation
• intravenous montelukast
• leukotriene receptor antagonist
• randomized trial

Acknowledgments

We thank Jennifer Pawlowski, MS, from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA, for her editorial assistance. We thank Dr. Tohru Tsuda (Tsuda Hospital), Dr. Naohito Suzuki (Doai Memorial Hospital), Dr. Kensuke Fukuyo (Fukuyo Naika Clinic), Dr. Shigeru Fujii (Fukuoka Shin Mizumaki Hospital), Dr. Masaharu Kinoshita (Nagata Hospital), Dr. Masahiko Tokushima (Maebashi Norte Hospital), Dr. Junichiro Hiyama (Shin-Koga Hospital), Dr. Toyotake Arisawa (Izumino Hospital), Dr. Takefumi Saito (National Hospital Organization Ibaraki Higashi Hospital), Dr. Koshi Ichihashi (Iida Hospital), Dr. Hiroshi Koto (Kyushu Central Hospital), Dr. Yuji Nakatani (Nakatani Hospital), Dr. Kazuo Nakanishi (Social Insurance Chukyo Hospital), Dr. Norio Kihara (Kihara Hospital), Dr. Ryuichiro Kobayashi (Ohta General Hospital Foundation Ohta Nishinouchi Hospital), Dr. Hiromasa Inoue (Kyushu University Hospital), Dr. Toshihiro Shirai (Shizuoka General Hospital), Dr. Masami Taniguchi (National Hospital Organization Sagamihara Hospital), Dr. Hirokazu Kubo (Kinki University Hospital), Dr. Takeshi Matsumura (Ibaraki Seinan Medical Center Hospital), Dr. Susumu Arai (Kitasato Institute Medical Center Hospital), Dr. Masahide Miyamoto (Ohta Fukushima General Hospital), Dr. Youichi Nakamura (Yokohama City Minato Red Cross Hospital), Dr. Kenichi Takahashi (Yokohama Minamikyosai Hospital), Dr. Kiyoshi Komuta (Osaka Police Hospital), Dr. Makoto Yamamoto (Obihiro Kousei Hospital), Dr. Fumio Sakamaki (Saiseikai Central Hospital), Dr. Kazuto Hirata (Osaka City University Hospital), Dr. Yoshimasa Tanikawa (Kamo Hospital), Dr. Takao Fujisawa (National Hospital Organization Mie Hospital), Dr. Terufumi Shimoda (National Hospital Organization Fukuoka Hospital), Dr. Sekiya Koyama (National Hospital Organization Chushin Matsumoto Hospital), Drs. Fumio Kokubu and Kenji Minoguchi (Showa University Hospital), Dr. Toshiyuki Kita (National Hospital Organization Kanazawa Medical Center), Dr. Tetsuyuki Morikawa (Yokohama Rousai Hospital), Dr. Nobuki Aoki (Shinrakuen Hospital), Dr. Tetsuo Hiramatsu (Komaki Municipal Hospital), Dr. Hirotaka Yasuba (Takatsuki Red Cross Hospital), Dr. Osamu Taguchi (Mie University Hospital), Dr. Kazuya Fukuoka (Hospital of Hyogo College of Medicine). Dr. Yasuto Nakatsumi (Kanazawa Municipal Hospital), Dr. Nobuharu Ohshima (National Hospital Organization Tokyo Hospital), Dr. Takeshi Fukuda (Dokkyo Medical University Hospital), Dr. Motokazu Kato (Kishiwada City Hospital), Dr. Tatsuya Abe (Tohoku KoseiNenkin Hospital), Hiroaki Kume (Nagoya University Hospital), Dr. Yasuhiro Yamazaki (National Hospital Organization Dohoku Hospital), Dr. Yoshinori Katada (National Hospital Organization Osaka-Minami Medical Center), Dr. Goro Kimura (National Hospital Organization Minami-Okayama Medical Center), Dr. Hidenori Ibata (National Hospital Organization Mie Chuo Medical Center), Dr. Mitsuhiro Kamimura (National Hospital Organization Disaster Medical Center), Dr. Koichi Nishi (Ishikawa Prefectural Central Hospital), Dr. Soichi Tachikawa (Fujita Health University Banbuntane Hotokukai Hospital), Drs. Michiaki Horiba and Joe Shindoh (Ogaki Municipal Hospital), Dr. Akira Iwashima (Nagaoka Chuo General Hospital), Drs. Naoki Fujimura and Toru Enokibori (Rakuwakai Otowa Hospital), Dr. Masaharu Hiraga (Nakamura Hospital), Dr. Masaaki Miyoshi (Research Institute for Neuroscience Southern TOHOKU Medical Clinic), Dr. Osamu Nemoto (Iwase Public Hospital), Dr. Shigeo Nakajima (Nishioka Hospital), Dr. Toshio Kiguchi (Tachikawa General Hospital), Dr. Kazuro Ogurusu (Kasaoka City Hospital), and Drs. Yoshinori Ashihara and Hidetoshi Tachibana (Oita Oka Hospital).

Declaration of Interest

This study was sponsored by MSD KK, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA.

SH and TI are employees of MSD KK and SSS is an employee of MSD USA (with both MSD KK and MSD USA being subsidiaries of Merck & Co., Inc., Whitehouse Station, NJ, USA), and all three may own or have options to own stock in the company. MA, HT, YT, and YS declare consultancy and grant remuneration from MSD.

All authors are responsible for the work described in this article and were involved in at least one of the following: [conception, design, acquisition, analysis, statistical analysis, interpretation of data] and [drafting the manuscript and/or revising the manuscript for important intellectual content]. All authors provided final approval of the version to be published. All authors meeting authorship requirements are listed, and no authors meeting requirements were excluded. The manuscript was collectively written by all named authors; no outside writing assistance was provided.