ElExacaftor in cystic fibrosis: two drugs good, thrEE drugs bEttEr For cystic fibrosis (CF) patients homozygous for the F508del mutation of the transmembrane conductance regulator (CFTR) protein, a combination of a CFTR potentiator and a corrector has been shown to be beneficial. This pharmaceutical funded doubleblinded randomised control trial (Heijerman et al, Lancet 2019;394:1940) examined the clinical outcomes with the addition of elexacaftor (a further corrector) or placebo to tezacaftor and ivacaftor on percent predicted forced expiratory volume in one second (ppFEV1) after four weeks of therapy. The study randomised 107 participants with stable CF. The addition of elexacaftor was associated with a significant improvement in ppFEV1 (10%, 95% CI 7.4 to 12.6; p<0.0001) and reduction in sweat chloride concentration (−45.1 mmol/L, 95% CI −50.1 to −40.1; p<0.0001). The regime was well tolerated. Although the trial was limited to four weeks, similar improvements in lung function and sweat chloride tests over this duration have previously been associated with sustained positive outcomes in areas such as exacerbation rates. In addition, the group published data on patients heterozygous for F508del (Middleton et al, NEJM 2019;381:1809) demonstrating similar physiological improvements. These two trials represent a significant development for patients with at least one F508del mutation — almost 90% of patients.

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杂志社

囊性纤维化中的 ElExacaftor：两种药物好，三种药物更好 对于跨膜电导调节剂 (CFTR) 蛋白的 F508del 突变纯合子的囊性纤维化 (CF) 患者，CFTR 增强剂和校正剂的组合已被证明是有益的。这项由制药公司资助的双盲随机对照试验 (Heijerman et al, Lancet 2019;394:1940) 检查了在 tezacaftor 和 ivacaftor 中添加 elexacaftor（一种进一步的校正剂）或安慰剂的临床结果，以预测一秒内用力呼气量的百分比 (ppFEV1 ) 经过四个星期的治疗。该研究随机分配了 107 名患有稳定 CF 的参与者。添加 elexacaftor 与 ppFEV1 显着改善（10%，95% CI 7.4 至 12.6；p<0.0001）和汗液氯化物浓度降低（-45.1 mmol/L，95% CI -50）相关。1 至 -40.1；p<0.0001)。该政权得到了很好的容忍。尽管试验仅限于 4 周，但在此期间肺功能和汗液氯化物测试的类似改善以前与急性加重率等领域的持续阳性结果有关。此外，该小组还发表了 F508del 杂合患者的数据（Middleton 等，NEJM 2019；381:1809）证明了类似的生理改善。这两项试验代表了至少有一个 F508del 突变的患者——几乎 90% 的患者的重大进展。在此期间，肺功能和汗液氯化物测试的类似改善以前与急性加重率等领域的持续阳性结果有关。此外，该小组还发表了 F508del 杂合患者的数据（Middleton 等，NEJM 2019；381:1809）证明了类似的生理改善。这两项试验代表了至少有一个 F508del 突变的患者——几乎 90% 的患者的重大进展。在此期间，肺功能和汗液氯化物测试的类似改善以前与急性加重率等领域的持续阳性结果有关。此外，该小组还发表了 F508del 杂合患者的数据（Middleton 等，NEJM 2019；381:1809）证明了类似的生理改善。这两项试验代表了至少有一个 F508del 突变的患者——几乎 90% 的患者的重大进展。