类风湿性关节炎是以慢性、对称性多滑膜关节炎和关节外病变为主要临床表现的自身免疫性疾病。
滑膜关节炎是类风湿性关节炎最重要的病变。炎性肥厚之滑膜是造成关节进行性破坏的主要原因。开放性手术切除关节滑膜，创伤大、后遗症多。
近日，美国食品药品管理局批准了辉瑞的Xeljanz(tofacitinib，托法替尼)，用于对氨甲喋呤治疗反应不足或不耐受的中度至重度活动性类风湿性关节炎成人患者的治疗。
类风湿性关节炎是一种自身免疫性疾病，由于人体免疫系统错误地攻击健康组织，导致关节及周围组织发生炎症。据美国疾病预防控制中心数据，在美国约有150万人受到类风湿性关节炎困扰。Xeljanz是一种2次/日的药物，其通过阻断Janus激酶发挥治疗作用。
FDA药物评价和研究中心肺、变态反应和风湿病产品部主任Badrul Chowdhury博士说：“托法替尼为对甲氨蝶呤治疗反应不佳的类风湿性关节炎患者提供了一种新的治疗选择”。
Generic Name and Formulations:
Tofacitinib 5mg tabs.

Company:
Pfizer Inc.

Indications for XELJANZ:
Treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX); may be used as monotherapy or in combination with MTX or other nonbiologic disease-modifying anti-rheumatic drugs (DMARDs). Do not use in combination with biologic DMARDs or potent immunosuppressants (eg, azathioprine, cyclosporine).

Adult Dose for XELJANZ:
5mg twice daily. Moderate-to-severe renal impairment or moderate hepatic impairment; concomitant potent CYP3A4 inhibitors, or drugs that result in both moderate CYP3A4 and potent CYP2C19 inhibition: 5mg once daily. Dose adjustments: see full labeling.

Children's Dose for XELJANZ:
Not established.

Pharmacological Class:
Janus kinase (JAK) inhibitor.

Rems:
YES

Warnings/Precautions:
Increased risk of serious or fatal infections (eg, TB, bacterial, viral, invasive fungal, or other opportunistic pathogens). Active infections: do not initiate therapy. Chronic or history of recurring infections. Travel to, or residence in, areas with endemic TB or mycoses. Conditions that predispose to infection. Test/treat latent TB infection prior to initiating therapy. Monitor closely if new infection, or active TB (even if initial latent test is negative) occurs; interrupt treatment if serious or opportunistic infection, or sepsis develops. Known malignancy. History of GI perforations. Monitor lymphocytes, neutrophils, hemoglobin at baseline and during treatment; do not initiate therapy if lymphocytes <500cells/mm3, ANC <1000cells/mm3, or hemoglobin <9g/dL. Severe hepatic impairment: not recommended. Routinely monitor liver enzymes; interrupt therapy if drug-induced liver injury suspected. Monitor lipids 4–8 weeks following initiation. Elderly. Pregnancy (Cat. C). Nursing mothers: not recommended.

Interactions:
Concomitant live vaccines: not recommended. Potentiated by potent CYP3A4 inhibitors (eg, ketoconazole), or drugs that result in both moderate CYP3A4 and potent CYP2C19 (eg, fluconazole) inhibition. Antagonized by potent CYP3A4 inducers (eg, rifampin). Concomitant immunosuppressants (eg, azathioprine, tacrolimus, cyclosporine) or corticosteroids may increase risk of infections.

Adverse Reactions:
Upper respiratory tract infections, headache, diarrhea, nasopharyngitis; serious or opportunistic infections, TB, malignancies (eg, lymphoma).

Metabolism:
Hepatic (CYP3A4, 2C19).

Elimination:
Renal.

Generic Availability:
NO

How Supplied:
Tabs—28, 60, 180