Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
BMJ. 2013 Apr 8;346:f1939. doi: 10.1136/bmj.f1939.
To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis.
Population based cohort study.
Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n = 10,878) or not (n = 42,198) with TNF inhibitors and matched general population comparators (n = 162,743).
The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer.
113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100,000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs.
Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.
研究肿瘤坏死因子（TNF）抑制剂治疗与类风湿关节炎中的恶性黑色素瘤、未接受生物药物治疗的类风湿关节炎患者的黑色素瘤风险，以及 TNF 抑制剂在类风湿关节炎中的所有部位癌症风险之间的潜在关联。
基于人群的队列研究。
2001-2010 年瑞典全国临床、健康和人口登记处前瞻性记录的数据。接受 TNF 抑制剂治疗（n=10878）或未接受治疗（n=42198）的类风湿关节炎患者，以及匹配的一般人群对照者（n=162743）。
主要结局是无任何类型侵袭性癌症既往史的人群中首次侵袭性黑色素瘤。使用 Cox 回归比较非生物药物治疗的类风湿关节炎患者与一般人群对照者，以及接受 TNF 抑制剂治疗的类风湿关节炎患者与未接受生物药物治疗的患者，估计危险比。次要结局包括原位黑色素瘤、第二原发黑色素瘤和所有部位癌症。
在未接受生物药物治疗的类风湿关节炎患者中，113 例发生了首次侵袭性黑色素瘤，而在一般人群对照队列中，393 例发生了黑色素瘤。与一般人群相比，未接受生物药物治疗的类风湿关节炎患者患黑色素瘤的风险无显著增加（危险比 1.2，95%置信区间 0.9 至 1.5）。在接受 TNF 抑制剂治疗的类风湿关节炎患者中，发生了 38 例侵袭性黑色素瘤；与未接受生物药物治疗的类风湿关节炎患者相比，这些患者黑色素瘤的风险增加（危险比 1.5，1.0 至 2.2；每 100000 人年增加 20 例）。接受 TNF 抑制剂治疗的类风湿关节炎患者发生第二原发黑色素瘤的风险虽非显著增加（危险比 3.2，0.8 至 13.1；n=3 例与 10 例）。
总体而言，与一般人群相比，未接受生物药物治疗的类风湿关节炎患者侵袭性黑色素瘤的风险并未增加。接受 TNF 抑制剂治疗的类风湿关节炎患者总体癌症风险无增加，但侵袭性黑色素瘤的相对风险增加 50%。鉴于绝对风险的微小增加，这些发现可能不会显著改变 TNF 抑制剂在临床实践中的总体风险效益平衡，但可能会在其他原因导致黑色素瘤风险较高的患者中产生影响。
