The new drug baricitinib is helpful for rheumatoid arthritis patients who have not responded to methotrexate

This study investigated the safety and efficacy of the new drug baricitinib (LY3009104). Patients had moderate to severe rheumatoid arthritis and an inadequate response to methotrexate (Trexall, Rheumatrex).

Methotrexate is the mainstay drug for the treatment of rheumatoid arthritis. However, not all patients have an optimal response to methotrexate and new therapies are needed to treat these patients.

Baricitinib works by blocking the protein Janus Kinase 1/2. This interferes with normal communication within the cells and reduces the production of proteins that can cause inflammation. This anti-inflammatory effect of baricitinib makes it a promising new drug for treating rheumatoid arthritis. However, further research relating to its efficacy and safety are required.

This study included 301 patients divided into 5 groups. 98 patients in received a once daily dose of placebo (a substance that has no therapeutic effect, used for control in testing new drugs). The other groups received a once daily dose of 1 mg (49 patients), 2 mg (52 patients), 4 mg (52 patients) or 8 mg (50 patients) of baricitinib for 12 weeks. Patients receiving 2 mg, 4 mg and 8 mg continued their treatment for an additional 12 weeks. Patients originally assigned to placebo or a 1 mg dose were reassigned to 2 mg twice daily or 4 mg once daily doses of baricitinib for weeks 12–24.

After 12 weeks, symptoms improved by at least 20% in more patients receiving 4 or 8 mg than in the placebo group (76% compared to 41%). 20% response was evaluated based on ACR20 (the American College of rheumatology 20 grade; a 20% improvement in rheumatoid arthritis based on decreases in the number of swollen and tender joints, pain and patient disability). Higher rates of patients receiving 4 to 8 mg also achieved 50% or 70% improvement in their rheumatoid arthritis after 12 weeks compared to placebo.

Patients receiving 4 mg of baricitinib had the highest rates of remission (a decrease in or disappearance of signs and symptoms of disease) after 12 weeks compared to patients receiving placebo (25% compared to 1%). Remission was evaluated using the Disease Activity Score for 28-joint counts and erythrocyte sedimenation rate (DAS28-ESR; ESR is a test that measures the level of inflammation in the body). 

Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups. Serious infections developed in three patients receiving baricitinib: 1 case of bronchitis and 2 cases of pneumonia were recorded. 

The authors concluded that baricitinib improved the signs and symptoms of rheumatoid arthritis in methotrexate inadequate responders with active disease. Baricitinib was well tolerated with no unexpected safety findings through week 24.

The study was funded by Eli Lilly and Company, Eli Lilly and Company are also involved in developing baricitinib. The drug baricitinib is not yet approved by the FDA for the management of rheumatoid arthritis.