FDA批准首个JAK抑制剂治疗类风湿关节炎

美国食品药品管理局(FDA)于11月6日宣布，已批准Janus激酶(JAK)抑制剂tofacitinib用于治疗对甲氨蝶呤应答不充分或不能耐受的中至重度类风湿关节炎(RA)成年患者。该药物有望改变部分RA患者的治疗经历。

Tofacitinib是一种炎性细胞因子JAK通路的小分子抑制剂，也是首个被批准用于治疗RA的该类口服药物。炎性细胞因子在RA发病机制中起着一定作用。

根据FDA的批准声明，该药物的获批附带了风险评估和降低策略(REMS)，强调了与该药物治疗相关的严重风险，并要求生产商辉瑞公司开展上市后研究。

FDA称，该药物的批准是基于7项研究的结果。研究表明，接受治疗的中至重度RA患者与安慰剂组相比，临床应答和身体功能得到改善。Tofacitinib与机会性感染等严重感染、结核病、癌症以及淋巴瘤风险增加相关，上述风险已列入该药品说明书中的黑框警告中。

该药物还与胆固醇和肝酶水平提高，以及血细胞计数降低有关。REMS要求提供包括告知患者有关药物安全性的用药指南，以及旨在使医务人员了解该药物相关严重风险的沟通计划。

上市后研究将对两种剂量的tofacitinib与另一种已批准用于RA治疗的药物进行比较。

在5月份的会议上，FDA关节炎顾问委员会以8:2的投票结果推荐批准tofacitinib用于RA患者，尽管委员会成员对其安全性的担忧挥之不去。

辉瑞将以商品名Xeljanz上市该药。另一种JAK抑制剂ruxolitinib(Jakafi)于2011年获准用于骨髓纤维化治疗。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

The Janus kinase inhibitor tofacitinib, a drug that has the promise to change the treatment experience for some patients with rheumatoid arthritis, has been approved to treat adults with moderately to severely active disease who have not responded adequately to or cannot tolerate methotrexate, the Food and Drug Administration announced on Nov. 6.

Tofacitinib is a small-molecule inhibitor of the Janus kinase (JAK) pathway of inflammatory cytokines that play a role in the pathogenesis of RA, and is the first drug in this class of oral drugs to be approved for RA.

It has been approved with a Risk Evaluation and Mitigation Strategy (REMS) that addresses the serious risks associated with treatment, and a requirement that the manufacturer, Pfizer, conduct a postmarketing study, according to the FDA’s statement announcing the approval.

Approval was based on the results of seven studies, which found that patients with moderately to severely active RA had improvements in clinical response and physical functioning, when compared with those on placebo. Tofacitinib was associated with an increased risk of serious infections, including opportunistic infections; tuberculosis; cancers; and lymphoma, which are described in the boxed warning in the drug’s label, the FDA said.

Treatment was also associated with increases in cholesterol and liver enzymes, and decreased blood counts. The REMS consists of a Medication Guide that includes information for patients about the drug’s safety and a communication plan that will educate health care providers about the serious risks associated with the treatment.

The postmarketing study will compare two doses of tofacitinib with another approved treatment for RA.

At a meeting in May, the FDA’s Arthritis Advisory Committee voted 8 to 2 to recommend approval of tofacitinib for patients with RA, although panel members had lingering safety concerns.

Pfizer is marketing the drug as Xeljanz. Another JAK inhibitor, ruxolitinib (Jakafi), was approved to treat myelofibrosis in 2011.