Shelton Edward, Laharie David, Scott Frank I, Mamtani Ronac, Lewis James D, Colombel Jean-Frederic, Ananthakrishnan Ashwin N
Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts.
Service d'Hépato-Gastroentérologie, University Bordeaux, Laboratoire de Bactériologie, Bordeaux, Pessac, France.
Gastroenterology. 2016 Jul;151(1):97-109.e4. doi: 10.1053/j.gastro.2016.03.037. Epub 2016 Apr 1.
BACKGROUND & AIMS: Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk.
We searched Medline, EMBASE, and conference proceedings for terms related to immune-mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and 1 of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random-effects meta-analysis was performed to calculate the pooled incidence rates as well as risk differences between the various treatments.
Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8 per 1000 p-y), immune-modulator therapy (36.2 per 1000 p-y), or no immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease showed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6 per 1000 p-y for immune-modulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43).
In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune-suppressive therapies for individuals with specific cancers.
医生经常会遇到患有免疫介导疾病且有恶性肿瘤病史的患者。关于这些患者免疫抑制治疗安全性的数据有限。已发表的研究规模较小，事件数量较少，无法对风险进行可靠估计。
我们在Medline、EMBASE以及会议论文集中搜索了从创刊至2015年4月与免疫介导疾病、免疫抑制治疗和癌症复发相关的术语。我们纳入了16项研究（9项针对类风湿关节炎患者，8项针对炎症性肠病患者，1项针对银屑病患者），并根据免疫抑制治疗类型（肿瘤坏死因子单克隆抗体[抗TNF]、传统免疫调节剂或无免疫抑制）对研究进行分层。进行随机效应荟萃分析以计算合并发病率以及各种治疗之间的风险差异。
我们的分析纳入了11702人，在先前诊断为癌症后进行了31258人年的随访评估。接受抗TNF治疗的个体（每1000人年3(3.8)例）、免疫调节剂治疗的个体（每1000人年36.2例）或未进行免疫抑制的个体（每1000人年37.5例）中癌症复发率相似，但接受联合免疫抑制的患者中癌症复发率在数值上更高（每1000人年54.5例）（所有P值均>.1）。对新发和复发性癌症分别进行亚组分析、免疫调节剂治疗类型或免疫介导疾病分析均显示相似结果，风险未增加。当在索引癌症后6年内开始免疫抑制治疗时，我们发现新发或原发性癌症的合并发病率值相似（免疫调节剂为每1000人年33.6例，抗TNF药物为每1000人年43.7例），而在索引癌症后6年以上开始免疫抑制治疗时（免疫调节剂为每1000人年32.9例，P = .86；抗TNF药物为每1000人年21.0例，P = .43）。
在对16项研究的荟萃分析中，我们观察到先前患有癌症且未接受免疫抑制、抗TNF治疗、免疫调节剂治疗或联合治疗的个体中癌症复发率相似。需要进行前瞻性研究以确定针对特定癌症个体重新开始免疫抑制治疗的最佳间隔时间。
