A new biologic therapy for RA patients who failed methotrexate

This study evaluated the safety and efficiency of a range of doses of tabalumab in alleviating the symptoms of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that results in inflammation, pain and damage to joints. Autoimmune diseases occur when the body’s own cells are attacked and destroyed by the immune system. If not appropriately treated, RA can lead to substantial loss of functioning and mobility.

B cells are white blood cells that play an integral role in the immune system. However, excessive production and survival of B cells can lead to autoimmunity, and this has been found to be the case in RA. BAFF is a protein that plays a fundamental role in B cell generation and maintenance, and it is therefore suggested that neutralizing this protein may be a therapeutic approach for targeting B cells in RA. Tabalumab is a drug that binds to and neutralizes BAFF. This study aimed to identify a range of safe and effective doses of tabalumab that improve the signs and symptoms of RA.

A total of 136 patients were randomly allocated to treatment with 30 mg, 60 mg or 160 mg of tabalumab, or placebo. The patients had not received previous biologic therapy (drugs that inhibit specific components of the immune system). The patients all showed signs of active disease despite previous treatment with methotrexate (Rheumatrex), a drug that interferes with the production of DNA and reduces inflammation. The primary outcome was the percentage of patients achieving a 20% improvement in disease variables. Statistical analyses were conducted in week 16.

At week 16, 57.6% of the 30-mg group, 67.6% of the 60-mg group, 51.5% of the 160-mg group and 29.4% of the placebo group achieved a 20% improvement in disease variables. The average number of tender joints decreased significantly for the 30-mg-group (-9), the 60-mg group (-10) and the 160-mg group (-8) compared to the placebo group (-4). The decrease in the average number of swollen joints was significant only for the 60-mg group (-8) and the 160-mg group (-7) compared to the placebo group (-5).  The disease activity score (a measurement of RA activity) was lower in the tabalumab groups than the placebo group. The disease activity score was below 3.2 in 13% of the 30-mg group, 3% of the 60-mg group, 6% of the 160-mg group and 2.9% of the placebo group. No patients in the placebo group or the 160-mg group achieved remission (absence of disease activity) compared with 3% in the 30-mg group and 3% in the 60-mg group.

Treatment-associated adverse events occurred in 46% of patients receiving placebo and 43% of patients receiving tabalumab. The most common adverse events were abdominal pain, nausea and headache. There were no dose-related increases in the frequency of adverse events. However, tabalumab caused a significant reduction in B cell counts over time, a trend that may increase a patients’ risk for infections.  

Tabalumab demonstrated encouraging efficiency in this small study, suggesting that neutralizing BAFF may be an effective therapy for patients with rheumatoid arthritis.

Tabalumab was developed by Eli-Lilly, the company who provided funding for this trial. Recently Eli-Lilly stated that they had discontinued their Phase III studies into tabalumab, due to a lack of efficacy.