Department of Internal Medicine, Bridgeport Hospital-Yale New Haven Health, Bridgeport, CT, USA.
Department of Internal Medicine, Quinnipiac University Frank H. Netter MD School of Medicine/Saint Vincent Medical Center, Bridgeport, CT, USA.
Pancreatology. 2019 Jun;19(4):587-594. doi: 10.1016/j.pan.2019.04.015. Epub 2019 May 2.
Systemic immune side effects including pancreatitis have been reported with the use of Immune Checkpoint Inhibitors (ICI) (CTLA-4, PD-1 and PDL-1). However, the true incidence, risk, causes (tumor or drug specific) of pancreatitis and relation to other immune side effects, especially diabetes mellitus (DM) are unknown.
We performed a systematic review and meta-analysis of all clinical trials using ICI for the incidence of any grade lipase elevation, pancreatitis or DM.
The incidence of asymptomatic lipase elevation after ICI use is 2.7% (211/7702) and grade 2 pancreatitis is 1.9% (150/7702). No pancreatitis related mortality has been reported in these clinical trials. Patients treated with CTLA-4 inhibitors have increased incidence of pancreatitis when compared to patients treated with PD1 inhibitors 3.98% (95% CI: 2.92 to 5.05) vs 0.94% (95% CI: 0.48 to 1.40); P value < 0.05. Patients treated with ICI for melanoma have increased incidence of pancreatitis when compared to non-melanoma cancers. We also noted an additive increase in incidence of pancreatitis with combination of CTLA4 and PD-1 inhibitors (10.60; 95% CI: 7.89 to 13.32) compared with either CTLA-4 or PD-1 inhibitors alone.
Our study provides precise data for the incidence of pancreatitis among patients using ICI based on tumor types and ICI regimens. ICI use for solid tumors is associated with increased incidence of all grades of lipase elevation and pancreatitis, especially for CTLA-4 agents and ICI combination. Although it does not appear to be associated with mortality, ICI related pancreatitis should be recognized early for appropriate treatment and to potentially reduce long term complications.
使用免疫检查点抑制剂（ICI）（CTLA-4、PD-1 和 PDL-1）会引起全身性免疫副作用，包括胰腺炎。然而，胰腺炎的真实发病率、风险、病因（肿瘤或药物特异性）以及与其他免疫副作用（尤其是糖尿病）的关系尚不清楚。
我们对所有使用 ICI 的临床试验进行了系统性回顾和荟萃分析，以评估任何级别脂肪酶升高、胰腺炎或糖尿病的发生率。
ICI 治疗后无症状性脂肪酶升高的发生率为 2.7%（211/7702），2 级胰腺炎的发生率为 1.9%（150/7702）。这些临床试验中未报告与胰腺炎相关的死亡。与 PD1 抑制剂相比，CTLA-4 抑制剂治疗的患者发生胰腺炎的风险更高 3.98%（95%CI：2.92 至 5.05）比 0.94%（95%CI：0.48 至 1.40）；P 值 < 0.05。与非黑色素瘤癌症相比，ICI 治疗黑色素瘤的患者发生胰腺炎的风险更高。我们还注意到，与单独使用 CTLA4 或 PD1 抑制剂相比，CTLA4 和 PD1 抑制剂联合使用时胰腺炎的发生率增加（10.60；95%CI：7.89 至 13.32）。
我们的研究基于肿瘤类型和 ICI 方案，为使用 ICI 的患者发生胰腺炎的发生率提供了精确数据。ICI 用于实体瘤与所有级别脂肪酶升高和胰腺炎的发生率增加有关，尤其是 CTLA-4 药物和 ICI 联合使用时。尽管它似乎与死亡率无关，但应及早识别与 ICI 相关的胰腺炎，以便进行适当的治疗，并有可能减少长期并发症。
