• Written By: Andrea D. Birnbaum, MD, PhD

    This two-year prospective study found that tofacitinib was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage.

    Methotrexate is a first-line treatment in the management of rheumatoid arthritis, but its use is limited by its side effects, hepatotoxicity, and overall efficacy in severe disease. Tofacitinib is a small-molecule Janus kinase (JAK) inhibitor that has shown success in the treatment of rheumatoid arthritis and other inflammatory disorders. But its use is also associated with side effects, and a recent study described serious adverse events in 15.4% of patients.

    In recent years, the medical community has been presented with new and exciting treatments for inflammatory diseases that offer patients better disease control and improved quality of life. As physicians embrace new treatments, such as TNF- and JAK- inhibitors, they must balance the increased level of immunosuppression with the inherently-associated increased risks of malignancy and infection. 

    The current study randomized 958 patients with moderate-to-severe rheumatoid arthritis to low-dose oral tofacitinib (5 mg twice daily), high-dose oral tofacitinib (10 mg twice daily), or methotrexate at a starting dose of 10 mg per week, increased by 5 mg per week every four weeks to 20 mg by week eight. 

    At 24 months, both tofacitinib doses were superior to methotrexate at reducing symptoms of rheumatoid arthritis and clinical signs of disease progression. All groups reported similar rates of adverse events, although patients treated with tofacitinib had higher rates of herpes zoster and three of the patients developed lymphoma.  

    One consideration in this study is the dose of methotrexate. Many uveitis specialists recommend 22.5 mg to 25 mg weekly to achieve quiescence. Use of a higher dose of methotrexate might be considered in future superiority studies, particularly if they involve treatment of ocular inflammation.