Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom.
Dermatology Centre, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, United Kingdom.
JAMA Dermatol. 2020 Jul 1;156(7):787-794. doi: 10.1001/jamadermatol.2020.1300.
Biologic therapies are widely prescribed immunomodulatory agents. There are concerns that compared with treatment with conventional systemic therapy, long-term biologic treatment for common immune-mediated inflammatory diseases, namely inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriasis, may be associated with increased risk of melanoma.
To examine whether biologic treatment of IBD, RA, or psoriasis is associated with an increased risk of melanoma compared with conventional systemic therapy.
Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published from January 1, 1995, to February 7, 2019, for eligible studies.
Randomized clinical trials, cohort studies, and nested case-control studies quantifying the risk of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with patients treated with conventional systemic therapy were included.
Two reviewers independently extracted key study characteristics and outcomes. Study-specific risk estimates were pooled, and random- and fixed-effects model meta-analyses were conducted. Heterogeneity was assessed using the I2 statistic. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed.
The pooled relative risk (pRR) of melanoma in biologic-treated patients with IBD, RA, and psoriasis compared with biologic-naive patients treated with conventional systemic therapy.
Seven cohort studies comprising 34 029 biologic-treated patients and 135 370 biologic-naive patients treated with conventional systemic therapy were eligible for inclusion. Biologic treatment was positively associated with melanoma in patients with IBD (pRR, 1.20; 95% CI, 0.60-2.40), RA (pRR, 1.20; 95% CI, 0.83-1.74), or psoriasis (hazard ratio, 1.57; 95% CI, 0.61-4.09) compared with those who received conventional systemic therapy, but the differences were not statistically significant. Adjustment for other risk factors was absent from most studies.
The findings suggest that clinically important increases in melanoma risk in patients treated with biologic therapy for common inflammatory diseases cannot be ruled out based on current evidence. However, further studies with large patient numbers that adjust for key risk factors are needed to resolve the issue of long-term safety of biologic therapy.
生物疗法是广泛应用的免疫调节药物。人们担心与传统的全身治疗相比，长期使用生物疗法治疗常见的免疫介导的炎症性疾病，如炎症性肠病（IBD）、类风湿关节炎（RA）和银屑病，可能会增加患黑色素瘤的风险。
研究与传统的全身治疗相比，生物疗法治疗 IBD、RA 或银屑病是否与黑色素瘤风险增加相关。
从 1995 年 1 月 1 日至 2019 年 2 月 7 日，在 Embase、MEDLINE 和 Cochrane 中央对照试验注册库（CENTRAL）中检索了有关 IBD、RA 和银屑病的生物治疗患者与接受传统全身治疗患者的黑色素瘤风险的随机临床试验、队列研究和巢式病例对照研究。
纳入了定量评估 IBD、RA 和银屑病的生物治疗患者与接受传统全身治疗患者的黑色素瘤风险的随机临床试验、队列研究和巢式病例对照研究。
两名审查员独立提取关键研究特征和结果。汇总了研究特异性风险估计值，并进行了随机和固定效应模型荟萃分析。使用 I2 统计量评估异质性。遵循了观察性研究的荟萃分析（MOOSE）报告指南。
与接受传统全身治疗的生物治疗患者相比，IBD、RA 和银屑病的生物治疗患者的黑色素瘤的合并相对风险（pRR）。
有 7 项队列研究纳入了 34029 名接受生物治疗的患者和 135370 名接受传统全身治疗的生物治疗患者。生物治疗与 IBD（pRR，1.20；95%CI，0.60-2.40）、RA（pRR，1.20；95%CI，0.83-1.74）或银屑病（风险比，1.57；95%CI，0.61-4.09）患者的黑色素瘤相关，但差异无统计学意义。大多数研究均未调整其他风险因素。
这些发现表明，根据现有证据，不能排除接受生物治疗的常见炎症性疾病患者黑色素瘤风险显著增加的可能性。然而，需要进一步开展具有大量患者数量且调整了关键风险因素的研究，以解决生物治疗的长期安全性问题。
