Sterling Timothy R, Moro Ruth N, Borisov Andrey S, Phillips Elizabeth, Shepherd Gillian, Adkinson Newton Franklin, Weis Stephen, Ho Christine, Villarino Margarita Elsa
Vanderbilt University School of Medicine, Nashville, Tennessee.
Centers for Disease Control and Prevention CDC Foundation, Research Collaboration, Atlanta, Georgia.
Clin Infect Dis. 2015 Aug 15;61(4):527-35. doi: 10.1093/cid/civ323. Epub 2015 Apr 22.
Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome.
We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study.
Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1).
SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.
NCT00023452.
对于高危人群的潜伏性结核感染，每周一次利福喷丁加异烟肼治疗3个月（3HP）与每日一次异烟肼治疗9个月（9H）效果相同，但有报道称可能出现类流感综合征。
我们在预防结核病研究中确定了具有临床意义的全身性药物反应（SDR），并评估了未完成治疗的患者的危险因素。
在接受≥1剂研究药物的7552人中，153人出现SDR：3HP组138/3893（3.5%），9H组15/3659（0.4%）（P<0.001）。在3HP组中，87人（63%）出现类流感综合征，23人（17%）出现皮肤反应；13/3893（0.3%）出现严重反应（6人低血压），6人报告晕厥。症状在中位3剂后出现，给药后4小时出现；症状缓解的中位时间为24小时。无死亡病例。在多因素logistic回归分析中，与SDR独立相关的因素包括接受3HP治疗（调整后的优势比[aOR]9.4；95%置信区间[CI]，5.5，16.2）、非西班牙裔白人种族/族裔（aOR 3.3；95%CI，2.3，4.7）、女性（aOR 2.0；95%CI，1.4，2.9）、年龄≥35岁（aOR 2.0；95%CI，1.4，2.9）和较低的体重指数（体重指数[BMI]；P = 0.009）。在接受3HP治疗的人群的另一项多因素分析中，严重SDR与非西班牙裔白人种族/族裔（aOR 5.4；95%CI，1.8，16.3）以及同时接受非研究药物治疗（aOR 5.9；95%CI，1.3，27.1）相关。
3HP治疗时SDR更常见，且大多为类流感样。白人、女性、年龄较大和BMI较低的人群风险增加。严重反应罕见，与3HP、同时用药和白人种族有关。潜在机制尚不清楚。
NCT00023452。
