Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Department of Gastroenterology, Centre Hospitalier Régional Universitaire-Nancy, Nancy, France; University of Lorraine, Inserm, Nutrition-Genetics and Exposure to Environmental Risks, Nancy, France.
Clin Gastroenterol Hepatol. 2024 Mar;22(3):499-512.e6. doi: 10.1016/j.cgh.2023.07.027. Epub 2023 Aug 12.
BACKGROUND & AIMS: There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments.
We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent.
Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation.
In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.
免疫介导性疾病合并恶性肿瘤病史患者使用免疫抑制治疗的安全性数据有限,尤其是新型生物制剂和小分子药物治疗的数据。
我们系统检索了 PubMed 和 Embase 数据库,以确定研究免疫介导性疾病中免疫抑制治疗对癌症复发影响的研究。使用随机效应荟萃分析对研究进行汇总,并按治疗类型进行分层。主要结局为新发癌症的发生,定义为新发或复发癌症。
我们的荟萃分析纳入了 31 项研究(17 项炎症性肠病、14 项类风湿关节炎、2 项银屑病和 1 项强直性脊柱炎),共纳入 24328 人,随访评估 85784 人年。未接受免疫抑制治疗(IS)者的癌症复发率相似(1627 例新发癌症,43765 人年;35/1000 人年;95%CI,27-43),接受肿瘤坏死因子拮抗剂(571 例新发癌症,17722 人年;32/1000 人年;95%CI,25-38)、免疫调节剂(1104 例新发癌症,17018 人年;46/1000 人年;95%CI,31-61)和联合免疫抑制治疗(179 例新发癌症,2659 人年;56/1000 人年;95%CI,31-81)者的癌症复发率相似。接受乌司奴单抗(5 例新发癌症,213 人年;21/1000 人年;95%CI,0-44)和维得利珠单抗(37 例新发癌症,1951 人年;16/1000 人年;95%CI,5-26)者癌症发生率较低,但尚无关于 JAK 抑制剂的研究。按免疫抑制治疗开始时间分层的研究未发现早期(<5 年)或延迟治疗开始与药物疗效相关。
在免疫介导性疾病合并恶性肿瘤病史的患者中,我们观察到无免疫抑制治疗与不同免疫抑制治疗的癌症复发率相似。