甲氨蝶呤治疗类风湿关节炎后发生淋巴细胞增生性疾病的风险研究

甲氨蝶呤(MTX)相关淋巴增生性疾病(MTX-LPD)是接受甲氨蝶呤治疗的类风湿关节炎(RA)患者面临的一个棘手的问题。然而，其发生率、预后和危险因素尚不清楚。

这项回顾性研究评估了MTX-LPD的实际发生率、预后影响和危险因素。在986例接受MTX治疗的RA患者中，90例患者发生了95次新的恶性肿瘤(NMs)，其中26例患者发生了最为常见的LPD。在MTX启动后的5年和10年，累计 LPD发生率分别为1.3%和4.7%。在24例发生LPD后停用甲氨蝶呤的患者中，有15例持续消退，LPD患者和无NM的患者总生存期无差异。炎症标志物和淋巴细胞绝对计数检测对早期LPD的检出无意义，但大多数LPD患者的红细胞沉降率持续升高。

对于联合用药，他克莫司只有在患者未接受生物疾病修饰抗风湿药物(bDMARDs)时才会增加风险。bDMARDs无增加任何药物的风险或使用类别的数量。即使在使用长时间MTX治疗后予IL-6A治疗，出现LPD病例数发病率仍较低，但差异无统计学意义。因此，在10年的MTX治疗中，大约每20例RA患者中有1例发生MTX-LPD，但这并不影响RA患者的生存。

他克莫司有增加某些患者发生LPD的风险，应谨慎使用。

Abstract Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.

引自:Tanaka K, Ichikawa A, Umezawa N, Yamamoto K, Yoshifuji K, Okada K, Nogami A, Umezawa Y, Nagao T, Sakashita C, Mori T, Tohda S, Koike R, Yasuda S, Yamamoto M. Lymphoproliferative disorder risk after methotrexate treatment for rheumatoid arthritis. Cancer Sci. 2023 Jun 26. doi: 10.1111/cas.15894. Epub ahead of print. PMID: 37365854.