Tofacitinib (Xeljanz®) is a disease-modifying antirheumatic drug (DMARD). It is now available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of severe active rheumatoid arthritis. Tofacitinib is an oral Janus kinase (JAK) inhibitor that reduces the production of pro-inflammatory cytokines. Cytokines have become important targets for the treatment of rheumatoid arthritis as they are associated with autoimmunity, chronic inflammatory synovitis, and the destruction of joint tissue.

Clinical trials demonstrate statistically superior response rates for tofacitinib compared to placebo, as measured by the American College of Rheumatology (ACR) criteria. The most frequently reported adverse effects are upper respiratory tract infections, headache, nasopharyngitis, and diarrhoea. Infections such as herpes zoster and pneumonia are the most common serious adverse reactions. Tofacitinib may be associated with a higher risk of herpes zoster infection with one study reporting an incidence of 4.0%, compared to 1.1% in the methotrexate-treated group.

Tofacitinib should not be used with other cytokine modulators or potent immunosuppressants due to the additive risk of infection. Tofacitinib is also contraindicated in patients with severe hepatic impairment. Hepatic metabolism by the cytochrome P450 system, primarily CYP3A4 with some contribution from CYP2C19, accounts for approximately 70% clearance of the parent drug. Dose reductions of tofacitinib are therefore recommended when coadministered with potent inhibitors of CYP3A4 or medications with both moderate inhibition of CYP3A4 and strong inhibition of CYP2C19. Conversely, tofacitinib efficacy may be reduced by potent inducers of CYP3A4, such as rifampicin.


  1. Hodge JA, Kawabata TT, Krishnaswami S, Clark JD, Telliez JB, Dowty ME, et al. The mechanism of action of tofacitinib – an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016; 34(2): 318-28.
  2. Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. New Engl J Med. 2014; 370(25): 2377-86.
  3. Xeljanz® (tofacitinib) Australian approved product information. West Ryde: Pfizer Australia. Approved February 2017.

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