. Unidade de Pneumologia Pediátrica, Instituto da Criança e do Adolescente, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.
. Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.
J Bras Pneumol. 2024 Jan 5;49(6):e20230187. doi: 10.36416/1806-3756/e20230187. eCollection 2024.
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
评估三联囊性纤维化跨膜电导调节因子（CFTR）调节剂（依伐卡托+泰比卡托+艾美拉唑）（ETI）治疗对囊性纤维化患者重要临床终点的影响。
这是一项系统评价和荟萃分析，纳入了比较 ETI 与安慰剂或其他 CFTR 调节剂联合治疗方案在至少携带一个 F508del 等位基因的 CF 患者中的疗效的随机临床试验。本研究遵循系统评价和荟萃分析报告的首选条目（PRISMA）建议以及患者（P）、干预措施（I）、比较措施（C）和结局（O）方法（PICO）。我们检索了 MEDLINE、EMBASE、Cochrane 对照试验中心注册库和 ClinicalTrials.gov 数据库，检索时间从建库至 2022 年 12 月 26 日。使用 Cochrane 偏倚风险工具评估偏倚风险，根据推荐评估、制定与评价（GRADE）分级评估证据质量。
我们在初步检索中检索到 54 项研究。其中，有 6 项研究符合纳入标准并进行了分析（共纳入 1127 例患者，干预组和对照组分别为 577 例和 550 例）。荟萃分析显示，ETI 治疗可增加 FEV1%[风险差（RD），+10.47%；95%可信区间，6.88-14.06]，减少急性肺恶化次数（RD，-0.16；95%可信区间，-0.28 至 -0.04），改善生活质量（RD，+14.93；95%可信区间，9.98-19.89）和 BMI（RD，+1.07 kg/m2；95%可信区间，0.90-1.25）。两组不良反应发生率无差异（RD，-0.03；95%可信区间，-0.08 至 0.01），且研究均未报告死亡事件。
我们的研究结果表明，ETI 治疗可显著改善具有临床意义的患者为中心的结局。
