Almutairi Abdulaali R, Slack Marion, Erstad Brian L, McBride Ali, Abraham Ivo
Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ, USA.
Ther Adv Drug Saf. 2021 Feb 2;12:2042098621991279. doi: 10.1177/2042098621991279. eCollection 2021.
The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting.
Elderly patients (age ⩾ 65 years) diagnosed with advanced melanoma between 2011 and 2015 and treated with anti-CTLA4 or anti-PD1 agents were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. We estimated the risk of colitis from start of treatment up to 90 days from the last dose of therapy. We used the log-rank test and logistic regression with adjustment for potential confounders using the inverse probability of treatment weighting method. We conducted several sensitivity analyses.
A total of 274 elderly patients with advanced melanoma were included in our cohort. The risk of colitis was similar between anti-PD1 users and anti-CTLA4 users based on log-rank test ( = 0.17) and logistic regression [odds ratio (OR) = 0.35, 95% confidence interval (95%CI) 0.04-2.79]. Sensitivity analyses for patients with all-stage melanoma showed a significantly lower risk of colitis in anti-PD1 compared with anti-CTLA4 treated patients based on log-rank test ( = 0.017) and logistic regression (OR = 0.21, 95%CI 0.09-0.53).
Elderly with advanced melanoma treated with anti-CTLA4 or anti-PD1 had a similar risk of developing colitis. However, there was a statistically significant difference in the risk of colitis between anti-CTLA4 or anti-PD1 users among all-stage-melanoma patients.
While the anti-cancer agents known as immune-checkpoint inhibitors have had a great impact on the treatment of melanoma, they may also have side effects. This study estimated the risk of colitis, a chronic inflammation of the colon, in elderly patients with melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) or anti-programmed cell-death 1 (anti-PD1) agents, using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Overall, we found that the risk of colitis was not different between anti-PD1 users and anti-CTLA4 users with advanced-stage melanoma. However, after including patients across all stages of melanoma, we found a significantly lower risk of colitis with anti-PD1 compared with anti-CTLA4.
在晚期黑色素瘤治疗中，使用抗细胞毒性T淋巴细胞抗原4（抗CTLA4）疗法（伊匹单抗）和抗程序性细胞死亡蛋白1（抗PD1）药物（纳武单抗和派姆单抗）与包括结肠炎在内的免疫相关不良事件（irAE）有关。我们旨在评估在现实环境中接受抗CTLA4和抗PD1治疗的老年晚期黑色素瘤患者中结肠炎的发生率和风险。
从监测、流行病学和最终结果（SEER）-医疗保险数据中识别出2011年至2015年间诊断为晚期黑色素瘤并接受抗CTLA4或抗PD1药物治疗的老年患者（年龄⩾65岁）。我们估计了从治疗开始到最后一剂治疗后90天内结肠炎的风险。我们使用对数秩检验和逻辑回归，并采用治疗权重逆概率方法对潜在混杂因素进行调整。我们进行了多项敏感性分析。
我们的队列中共有274例老年晚期黑色素瘤患者。基于对数秩检验（P = 0.17）和逻辑回归[比值比（OR）= 0.35，95%置信区间（95%CI）0.04 - 2.79]，抗PD1使用者和抗CTLA4使用者之间的结肠炎风险相似。对所有分期黑色素瘤患者的敏感性分析显示，基于对数秩检验（P = 0.017）和逻辑回归（OR = 0.21，95%CI 0.09 - 0.53），与抗CTLA4治疗的患者相比，抗PD1治疗的患者结肠炎风险显著更低。
接受抗CTLA4或抗PD1治疗的老年晚期黑色素瘤患者发生结肠炎的风险相似。然而，在所有分期黑色素瘤患者中，抗CTLA4或抗PD1使用者之间的结肠炎风险存在统计学显著差异。
虽然被称为免疫检查点抑制剂的抗癌药物对黑色素瘤治疗产生了重大影响，但它们也可能有副作用。本研究使用监测、流行病学和最终结果（SEER）-医疗保险链接数据库中的数据，评估了接受抗细胞毒性T淋巴细胞抗原4（抗CTLA4）或抗程序性细胞死亡蛋白1（抗PD1）药物治疗的老年黑色素瘤患者患结肠炎（一种结肠慢性炎症）的风险。总体而言，我们发现晚期黑色素瘤的抗PD1使用者和抗CTLA4使用者之间的结肠炎风险没有差异。然而，在纳入所有分期黑色素瘤患者后，我们发现与抗CTLA4相比，抗PD1治疗的患者结肠炎风险显著更低。
