Nakagawa Taku, Fujita Kohei, Miki Mari, Ito Akihiro, Namkoong Ho, Asakura Takanori, Morimoto Kozo, Hasegawa Naoki, Kita Toshiyuki, Watanabe Akira, Tsuyuguchi Kazunari, Kawashima Masahiro, Shiozawa Ayako, Watanabe Satoru, Sato Atsuo, Kato Tatsuo, Kimizuka Yoshifumi, Harada Hiroaki, Fujita Kaori, Saito Akiko M, Hashimoto Hiroya, Inoue Yoshikazu, Ogawa Kenji
Department of Respiratory Medicine, NHO Higashinagoya National Hospital, Aichi, Japan.
Department of Respiratory Medicine, NHO Kyoto Medical Center, Kyoto, Japan.
Ann Am Thorac Soc. 2025 Aug;22(8):1183-1192. doi: 10.1513/AnnalsATS.202406-626OC.
Patients with noncavitary nodular bronchiectatic (NB) complex pulmonary disease (MAC-PD) are treated intermittently three times per week, although no randomized controlled trials have been conducted comparing three times weekly with daily therapy. To assess the tolerability, safety, and efficacy of intermittent versus daily treatment in patients with previously untreated noncavitary NB MAC-PD. In an open-label study, patients were randomly assigned to the intermittent therapy group receiving clarithromycin 1,000 mg, rifampicin 600 mg, and ethambutol 25 mg/kg (maximum 1,000 mg) three days per week or the daily therapy group receiving clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 15 mg/kg (maximum 750 mg) daily for 1 year. The primary endpoint was the proportion of patients requiring modification of the initial treatment regimen. Twenty-one Japanese hospitals participated in the study, enrolling 141 patients between May 2019 and December 2021. The full analysis set included 138 participants (intermittent therapy = 70; daily therapy = 68). There were no significant differences between the intermittent and daily therapy groups in terms of the regimen modification rate (20.0% [14 of 70] vs. 33.8% [23 of 68]; adjusted odds ratio, 0.48; 95% confidence interval, 0.22 to 1.05; = 0.06) or culture conversion (70.3% vs. 80.0%; = 0.53), time to culture conversion (28.0 vs. 28.5 d; = 0.89), improvement in chest CT findings (60.9% vs. 71.0%; = 0.30), or clarithromycin resistance development (1.4% vs. 0%; = 1.00). Elevated aspartate aminotransferase (16.9% vs. 41.2%; = 0.003) and alanine aminotransferase (18.3% vs. 44.1%; = 0.002) were more common in the daily treatment group, whereas elevated bilirubin (11.3% vs. 1.5%; = 0.04) and dysgeusia (14.1% vs. 1.5%; = 0.01) were more common in the intermittent treatment group. The daily treatment group exhibited a greater absolute change in the 36-Item Short Form Health Survey physical aspect score (-2.5 points) than the intermittent treatment group (2.1 points) ( = 0.01). Intermittent treatment was not significantly better tolerated than daily treatment for noncavitary NB MAC-PD. However, further studies with larger numbers of patients are needed. Clinical trial registered with https://jrct.mhlw.go.jp/en-top (jRCTs031190008).
非空洞性结节性支气管扩张（NB）型复杂性肺部疾病（MAC-PD）患者每周接受三次间歇性治疗，不过尚未进行随机对照试验来比较每周三次治疗与每日治疗的效果。为评估既往未接受治疗的非空洞性NB型MAC-PD患者间歇性治疗与每日治疗的耐受性、安全性及疗效。在一项开放标签研究中，患者被随机分配至间歇性治疗组，每周三天接受克拉霉素1000mg、利福平600mg及乙胺丁醇25mg/kg（最大剂量1000mg）治疗，或每日治疗组，每日接受克拉霉素800mg、利福平450mg及乙胺丁醇15mg/kg（最大剂量750mg）治疗，为期1年。主要终点是需要修改初始治疗方案的患者比例。21家日本医院参与了该研究，在2019年5月至2021年12月期间招募了141例患者。完整分析集包括138名参与者（间歇性治疗组 = 70例；每日治疗组 = 68例）。间歇性治疗组与每日治疗组在方案修改率（20.0%[70例中的14例]对33.8%[68例中的23例]；调整后的优势比为0.48；95%置信区间为0.22至1.05；P = 0.06）、培养转阴率（70.3%对80.0%；P = 0.53）、培养转阴时间（28.0天对28.5天；P = 0.89）、胸部CT表现改善（60.9%对71.0%；P = 0.30）或克拉霉素耐药发生率（1.4%对0%；P = 1.00）方面无显著差异。每日治疗组天门冬氨酸氨基转移酶升高（16.9%对41.2%；P = 0.003）和丙氨酸氨基转移酶升高（18.3%对44.1%；P = 0.002）更为常见，而间歇性治疗组胆红素升高（11.3%对1.5%；P = 0.04）和味觉障碍（14.1%对1.5%；P = 0.01）更为常见。每日治疗组在36项简明健康调查问卷身体方面得分的绝对变化（-2.5分）大于间歇性治疗组（2.1分）（P = 0.01）。对于非空洞性NB型MAC-PD，间歇性治疗的耐受性并不显著优于每日治疗。然而，需要更多患者参与的进一步研究。临床试验已在https://jrct.mhlw.go.jp/en-top（jRCTs031190008）注册。
