Ramsey Mitchell L, Li Susan S, Lara Luis F, Gokun Yevgeniya, Akshintala Venkata S, Conwell Darwin L, Heintz John, Kirkby Stephen E, McCoy Karen S, Papachristou Georgios I, Patel Alpa, Singh Vikesh K, Hart Phil A
Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Division of General Internal Medicine, The Ohio State University Wexner Medical Center, USA.
J Cyst Fibros. 2023 Mar;22(2):193-200. doi: 10.1016/j.jcf.2022.08.008. Epub 2022 Aug 23.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes.
We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included.
Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7).
CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.
囊性纤维化跨膜传导调节因子（CFTR）调节剂可改善囊性纤维化（CF）患者的肺部预后；然而，其对胰腺表现的影响尚未得到充分描述。我们推测CFTR调节剂可改善外分泌胰腺功能指标及预后。
我们进行了一项系统检索，以确定报告CFTR调节剂治疗的人类外分泌胰腺指标的研究。仅纳入报告基线和治疗期评估的研究。
在630项检索到的研究中，41项符合纳入标准。CFTR调节剂总体上使急性胰腺炎事件减少了85%（率比0.15，95%置信区间（CI）0.04，0.52），在胰腺功能充足的CF（PS-CF）亚组中效果更明显（率比0.13（95%CI 0.03，0.53））。在293例有胰腺功能充足基线和治疗期评估的受试者中，253例基线时胰腺功能不全，54例（21.3%）转变为胰腺功能充足。在32例基线FE-1值<200 mcg/g的受试者中，16例（50%）升至≥200 mcg/g。血清胰蛋白酶平均降低565.9 ng/mL（标准差（SD）311.8），淀粉酶降低38.2 U/L（SD 57.6），脂肪酶降低232.3 U/L（SD 247.7）。
使用CFTR调节剂可降低急性胰腺炎发生率，并改善外分泌胰腺功能的间接指标。有必要开展进一步的干预性研究，以评估CFTR调节剂对CFTR功能障碍患者急性胰腺炎和胰腺功能充足的作用机制及影响。
