Tofacitinib versus methotrexate in rheumatoid arthritis

This study compared methotrexate (Rheumatrex, Trexall) and tofacitinib (Xeljanz, Jakvinus) in patients suffering from rheumatoid arthritis (RA). 

Methotrexate is currently the preferred initial treatment for patients with RA. However, some concern exists around the associated side effects and safety. In some studies as many as 33% of patients stopped the drug after only 2 years of treatment. For this reason it is important to develop new drugs, with lower safety concerns. Tofacitinib is a new drug approved for use in RA. It is an oral drug which helps reduce inflammation. The aim of this study was to compare the two drugs for clinical benefits and safety.

This study included 958 adult patients, with active disease, who had never been treated with methotrexate before. The patients were assigned to three groups: group 1 received 5 mg of tofacitinib twice daily, group 2 received 10 mg of tofacitinib twice daily, and group 3 received increasing doses of methotrexate (up to 20 mg).

Tofacitinib was more successful than methotrexate at inducing remission (a decrease in or disappearance of signs and symptoms). After 6 months of treatment an average of 12% of patients receiving methotrexate had reduced the number of tender and swollen joints by 70%. This is compared to 25.5% of patients in the 5 mg tofacitinib group and 37.7% of patients in the 10 mg tofacitinib group.

A high number of adverse events occurred with both tofacitinib and methotrexate. Over 70% of patients from each group had some adverse event and over 10% had serious adverse events. This led to 11% of patients stopping their drug treatment. More serious adverse events included: shingles (4% of the tofacitinib and 1.1% of the methotrexate treatment group); cancer (0.65% of the tofacitinib and 0.54% of the methotrexate treatment group); death (0.52% of the tofacitinib and none of the methotrexate treatment group). There were also changes to patients’ laboratory test results. Blood levels of important immune cells needed to fight off infections decreased after all treatments, but this was most severe after treatment with 10 mg of tofacitinib. Patients treated with tofacitinib also had increased levels of cholesterol in blood samples. 

The authors concluded that tofacitinib was better than methotrexate at reducing signs and symptoms of rheumatoid arthritis. However, it caused more severe adverse effects. The benefit of tofacitinib needs to be carefully considered in the context of these risks.

The study was funded by Pfizer, who also discovered and developed the drug.