Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Mult Scler Relat Disord. 2022 Mar;59:103681. doi: 10.1016/j.msard.2022.103681. Epub 2022 Feb 9.
S1P receptor modulators are oral Disease-Modifying Therapies (DMTs) for Multiple Sclerosis, which were associated with cases of basal cell carcinoma in clinical trials. This study aims at investigating in a real-world adverse event reporting system whether S1P receptor modulators increase the risk of skin cancer reporting, compared to other DMTs.
Adverse event reports from the FDA Adverse Event Reporting System (FAERS) were extracted, cleaned, and analyzed from 2004Q1 until 2020Q4. The crude and adjusted Reported Odds Ratios (cROR, aROR) for the outcomes: basal cell carcinoma, squamous cell carcinoma, or melanoma were calculated for all DMTs. In a sensitivity analysis, we looked at each outcome separately.
The aROR (95%CI) of siponimod was: 9.68 (5.48-15.79) and of fingolimod 4.54 (3.86-5.32), indicating a safety signal of S1P receptor modulators for skin cancer. Ozanimod had only 52 complete reports without any cases. In the sensitivity analysis, siponimod showed a signal only for basal cell carcinoma: 22.83 (12.27-38.83), while fingolimod for all outcomes separately, including melanoma: 3.02 (2.31-3.89). Notably, among the other DMTs, alemtuzumab: 4.40 (2.98-6.25) and cladribine: 3.28 (1.17-7.13) presented also a signal for disproportionate reporting, while ocrelizumab showed a signal in the sensitivity analysis only for melanoma 2.55 (1.21-4.65).
S1P receptors seem to increase skin cancer reporting on FAERS, and the association is strongest for basal cell carcinomas. Therefore, close dermatologic surveillance before- and during therapy is needed. Whether fingolimod and ocrelizumab also increase the risk of melanoma needs further investigation.
鞘氨醇 1 型受体调节剂是多发性硬化症的口服疾病修正治疗药物（DMT），在临床试验中与基底细胞癌病例有关。本研究旨在通过真实世界的不良事件报告系统调查鞘氨醇 1 型受体调节剂与其他 DMT 相比是否会增加皮肤癌报告的风险。
从 2004 年第一季度到 2020 年第四季度，从 FDA 不良事件报告系统（FAERS）中提取、清理和分析不良事件报告。为所有 DMT 计算了基底细胞癌、鳞状细胞癌或黑色素瘤的未调整和调整后的报告比值比（cROR，aROR）。在敏感性分析中，我们分别观察了每个结果。
西尼莫德的 aROR（95%CI）为：9.68（5.48-15.79），芬戈莫德为 4.54（3.86-5.32），表明 S1P 受体调节剂有皮肤癌的安全信号。奥扎尼莫德仅有 52 份完整报告，没有任何病例。在敏感性分析中，西尼莫德仅对基底细胞癌有信号：22.83（12.27-38.83），而芬戈莫德对所有结果均有信号，包括黑色素瘤：3.02（2.31-3.89）。值得注意的是，在其他 DMT 中，阿仑单抗：4.40（2.98-6.25）和克拉屈滨：3.28（1.17-7.13）也显示出不成比例报告的信号，而奥瑞珠单抗在敏感性分析中仅对黑色素瘤有信号 2.55（1.21-4.65）。
S1P 受体似乎会增加 FAERS 中的皮肤癌报告，基底细胞癌的关联最强。因此，在治疗前和治疗期间需要进行密切的皮肤科监测。芬戈莫德和奥瑞珠单抗是否也会增加黑色素瘤的风险还需要进一步研究。
