Efficacy and safety of nemolizumab in paediatric patients aged 6–12 years with atopic dermatitis with moderate-to-severe pruritus: results from a phase III, randomized, double-blind, placebo-controlled, multicentre study
Atsuyuki Igarashi, Toshio Katsunuma, Takayo Matsumura, Hiroshi Komazaki, for the Nemolizumab-JP04 Study Group, Hidetoshi Takahashi, Katsushi Miura, Satoshi Horino, Shigemi Yoshihara, Shozo Maeda, Masayuki Akashi, Yuko Hamahata, Yoko Nezu, Kei Masuda, Seigo Shirakawa, Toshio Katsunuma, Yukihiro Ohya, Noriyuki Yanagida, Hiromi Tadaki, Masao Fukuzawa, Hideo Kaneko, Kazuhiro Takahashi, Michinori Funato, Masaki Futamura, Masanari Kodera, Yoshihiro Takasato, Takao Fujisawa, Akihiro Kume, Takeshi Taketani, Youko Murakami, Masatoshi Wakatsuki, Satomi Igawa, Minako Tomiita, Shuichi Suzuki, Masami Narita, Koichi Yoshida, Yasuto Kondo, Takahiro Kiyomasu, Yutaka Takemura, Akira Manki, Michihiro Hide, Akio Tanaka, Junichiro Tezuka, Masanori Ikeda, Fumiya Yamaide, Taiji Nakano
Abstract
BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory skin condition affecting up to one-quarter of children. Uncontrolled pruritus associated with childhood AD, and the accompanying scratching, negatively impacts quality of life (QoL), sleep and development. The humanized monoclonal antibody nemolizumab, used concomitantly with topical agents, was shown to reduce pruritus and improve QoL in patients with AD aged ≥ 13 years. However, data relating to its efficacy and safety in younger children (aged < 13 years) have been lacking. OBJECTIVES: To evaluate the efficacy and safety of nemolizumab, administered concomitantly with topical agents, in Japanese paediatric patients (aged 6-12 years) with AD and inadequately controlled moderate-to-severe pruritus. METHODS: This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre, 16-week, phase III study. Patients aged ≥ 6 and < 13 years, with confirmed AD, and an inadequate pruritic response despite treatment with topical agents and oral antihistamines were randomly assigned (1 : 1) to receive nemolizumab 30 mg or placebo every 4 weeks (Q4W). The primary efficacy endpoint was the change in the weekly mean 5-level itch score from baseline to week 16; secondary efficacy endpoints were related to pruritus, indicators for AD and QoL. Safety was assessed via adverse events (AEs) and laboratory test results. RESULTS: In total, 89 patients were enrolled, received either nemolizumab 30 mg (n = 45) or placebo (n = 44) Q4W, and completed the study. The mean patient age was 9.1 (SD 1.9) years, and mean duration of AD was 8.5 (2.7) years. The change in 5-level itch score from baseline to week 16 showed a statistically significant difference in the nemolizumab treatment group (-1.3) compared with placebo (-0.5; least-squares mean difference -0.8, 95% confidence interval -1.1 to -0.5; P < 0.0001). Improvements with nemolizumab were observed from the second day of administration. Secondary endpoints were in favour of nemolizumab. No AEs resulted in discontinuation, and the overall safety profile in patients aged 6-12 years was comparable with that in older patients (aged ≥ 13 years) with AD. CONCLUSIONS: Nemolizumab is a potential new treatment option for paediatric patients with AD whose pruritus has not been sufficiently improved with topical treatments and antihistamines.