An analysis of TNF-blocking agents in combination with methotrexate for active rheumatoid arthritis

This analysis investigated the benefits of combined methotrexate (MTX) and tumor necrosis factor (TNF) blockers in the treatment of active rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by the improper activation of the immune system leading to chronic inflammation and joint damage. Active RA is often treated with methotrexate, a commonly used anti-metabolite drug which inhibits the function of all highly active cells, including those of the immune system. TNF is an important signaling molecule involved in the regulation of immune and inflammatory processes. TNF is known to play a key role in the inflammation of the joints during active RA. Currently, five TNF-blocking agents are approved by the US Food and Drug administration for the treatment of RA; infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), and certolizumab pegol (Cimzia). This meta-analysis (an analysis of data combined from several similar studies) examined whether a combination therapy including TNF-blockers and methotrexate is more beneficial than methotrexate alone in the treatment of active RA.

Three randomized trials, including a total of more than 1000 patients, were included in this analysis. Each trial reported response to a different TNF-blocking agent in combination with methotrexate according to the American College of Rheumatology (ACR) response criteria (indicating the level of improvement in inflamed or tender joints, pain and joint function).

Overall, analysis showed that the combination of methotrexate with TNF inhibitors was significantly more effective than methotrexate therapy alone according to ACR response criteria. Achieving excellent response to therapy was determined to be 3.4-times more likely among patients receiving combined therapy. Achieving good response to therapy was determined to be 2.6-times more likely among patients receiving combined therapy. In addition, a significant decline was noted in the rate of patients withdrawing from treatment due to lack of efficiency among those receiving combined therapy. However, no significant difference was noted in the rate of patients withdrawing from treatment due to side-effects.

When analyzing results according to the different TNF-blockers used, no clear difference was noted between infliximab and adalimumab in response to treatment or withdraw from treatment rates. However, analysis suggested that patients receiving etanercept in combination with methotrexate were less likely to achieve good or excellent response to treatment than those treated with either infliximab or adalimumab.

This analysis concluded that the combination of methotrexate and TNF blocking agents is significantly more effective at treating active RA than methotrexate therapy alone.

Consult with your physician regarding the risk and benefits of TNF-blocking agents in the treatment of RA.