Sauer Sara M, Mitnick Carole D, Khan Uzma, Hewison Catherine, Bastard Mathieu, Holtzman David, Law Stephanie, Khan Munira, Padayachee Shrivani, Ahmed Saman, Isani Afshan K, Krisnanda Aga, Vilbrun Stalz Charles, Bektasov Sagit, Kumsa Andargachew, Docteur Wisney, Tintaya Karen, McNicol Mark, Atshemyan Hakob, Voynilo Tatiana, Thwe Thin Thin, Seung Kwonjune, Rich Michael, Huerga Helena, Khan Palwasha, Franke Molly
medRxiv. 2023 May 29:2023.05.24.23290472. doi: 10.1101/2023.05.24.23290472.
Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up.
We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights.
The estimated TB recurrence risk was 6.6 per 1000 (95% confidence interval (CI):3.2,11.2) when deaths were handled as non-recurrences, and 6.7 per 1000 (95% CI:2.8,12.2) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 24.2 (95% CI:14.1,37.0), 10.5 (95% CI:5.6,16.6), and 7.8 (95% CI:3.9,13.2) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small but apparent impact on estimates.
The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.
成功治疗后复发风险的量化对于评估耐多药或利福平耐药（MDR/RR）结核病（TB）的治疗方案至关重要。然而，当一些患者在治疗后随访期间死亡或失访时，此类分析会变得复杂。
我们分析了2015年至2018年期间在16个国家成功完成包含贝达喹啉和/或地拉曼胺的较长疗程MDR/RR-TB治疗方案的1991例患者的数据。我们使用五种处理治疗后死亡的方法，总体上以及按HIV状态估计治疗后六个月的结核病复发风险。我们使用逆概率加权法来处理失访患者，并研究了在不应用逆概率权重的情况下排除这些患者所产生的潜在偏倚的影响。
当将死亡视为未复发时，估计的结核病复发风险为每1000人中有6.6例（95%置信区间（CI）：3.2，11.2）；当对死亡进行截尾处理并应用逆概率权重来处理排除的死亡时，估计风险为每1000人中有6.7例（95%CI：2.8，12.2）。对于复发或1）任何死亡、2）死因不明或与结核病相关的死亡、3）与结核病相关的死亡，每1000人的复合复发结局估计风险分别为24.2（95%CI：14.1，37.0）、10.5（95%CI：5.6，16.6）和7.8（95%CI：3.9，13.2）。HIV状态的相应相对风险在方向和幅度上有所不同。在不进行逆概率加权的情况下排除失访患者对估计值有微小但明显的影响。
估计的六个月结核病复发风险较低，并且由于复发事件较少，与HIV状态的关联尚无定论。通过对死亡进行明确假设并对缺失的随访数据进行适当调整，将提高治疗后复发的估计。
