Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study

Atsushi Fukunaga; Yasumasa Kakei; Sae Murakami; Yuji Kan; Koji Masuda; Masatoshi Jinnin; Ken Washio; Hiroo Amano; Tohru Nagano; Akihisa Yamamoto; Toshihiro Otsuka; Shunsuke Takahagi; Motoi Takenaka; Naoko Ishiguro; Koremasa Hayama; Naoko Inomata; Yukinobu Nakagawa; Akiko Sugiyama; Michihiro Hide

doi:10.3389/fimmu.2024.1441478

Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study

Front Immunol. 2024 Sep 16:15:1441478. doi: 10.3389/fimmu.2024.1441478. eCollection 2024.

Authors

Atsushi Fukunaga^{1

2}, Yasumasa Kakei^{3

4}, Sae Murakami⁴, Yuji Kan⁵, Koji Masuda⁶, Masatoshi Jinnin⁷, Ken Washio⁸, Hiroo Amano⁹, Tohru Nagano¹⁰, Akihisa Yamamoto¹¹, Toshihiro Otsuka¹, Shunsuke Takahagi¹², Motoi Takenaka¹³, Naoko Ishiguro¹⁴, Koremasa Hayama¹⁵, Naoko Inomata¹⁶, Yukinobu Nakagawa¹⁷, Akiko Sugiyama¹⁸, Michihiro Hide^{12

19}

Affiliations

¹ Department of Dermatology, Division of Medicine for Function and Morphology of Sensory Organs, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
² Department of Dermatology, Kobe University Graduate School of Medicine, Kobe, Japan.
³ Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
⁴ Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan.
⁵ Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁶ Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
⁷ Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
⁸ Department of Dermatology, Kobe City Nishi-Kobe Medical Center, Kobe, Japan.
⁹ Department of Dermatology, Iwate Medical University School of Medicine, Shiwa-gun, Japan.
¹⁰ Department of Dermatology, Kobe City Medical Center General Hospital, Kobe, Japan.
¹¹ Department of Dermatology, Takarazuka City Hospital, Takarazuka, Japan.
¹² Department of Dermatology, School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
¹³ Department of Dermatology, Nagasaki University School of Biomedical Sciences, Nagasaki, Japan.
¹⁴ Department of Dermatology, Tokyo Women's Medical University, Shinjuku-ku, Japan.
¹⁵ Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan.
¹⁶ Department of Environmental Immuno-Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
¹⁷ Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
¹⁸ Department of Allergology, National Hospital Organization (NHO), Fukuoka National Hospital, Fukuoka, Japan.
¹⁹ Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.

Abstract

Background: For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2^nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU.

Methods: This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration.

Results: Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively.

Conclusions: Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile.

Clinical trial registration: https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.

Keywords: Japan; chronic spontaneous urticaria; histamine H1 antagonists; quality of life; sleepiness; switching to bilastine.

Publication types

Multicenter Study
Randomized Controlled Trial
Clinical Trial, Phase IV
Comparative Study

MeSH terms

Adult
Aged
Benzimidazoles / administration & dosage
Benzimidazoles / adverse effects
Benzimidazoles / therapeutic use
Chronic Urticaria* / drug therapy
Female
Histamine H1 Antagonists* / administration & dosage
Histamine H1 Antagonists* / adverse effects
Histamine H1 Antagonists* / therapeutic use
Humans
Male
Middle Aged
Piperidines* / administration & dosage
Piperidines* / adverse effects
Piperidines* / therapeutic use
Treatment Outcome
Young Adult

Substances

bilastine
Piperidines
Histamine H1 Antagonists
Benzimidazoles