What is the drug of choice after the failure of a TNF-inhibitor

This review discusses the choice of second-line treatment when patients fail to respond to a first tumor necrosis factor (TNF)-inhibitor in rheumatoid arthritis.

Common treatments for rheumatoid arthritis (RA) include biologic disease-modifying antirheumatic drugs (DMARDs), such as tumor necrosis factor (TNF)-inhibitors. These inhibitors block the activity of a protein called TNF, which is an inflammatory key factor in the pathology of RA. However, it has been found that this treatment does not work or causes negative side effects in up to 33% of patients. While there are other types of biologic DMARDs that block other factors related to inflammation, there is no consensus as to which is best to use after the failure of a TNF-inhibitor, or whether it is more effective to try a second TNF-inhibitor. The focus of the current article is the order in which biologic DMARDs may be most helpful in RA treatment.

Observational studies, which do not include direct comparisons between drugs as clinical trials do, have shown that switching to a second TNF-inhibitor following the failure of a first can improve disease symptoms or lead to disease remission, a time when the disease is not active, in up to 40% of patients. These results were most often found in studies involving the TNF-inhibitor etanercept (Enbrel).  Another study, though, found that switching to rituximab (Rituxan), which inhibits CD20, another protein involved in inflammation, led to a better response than switching to another TNF-inhibitor.

However, it is not clear from these studies how to determine which patients would benefit from either type of drug. The disease characteristics of each individual patient could mean a better response to certain treatments. For example, rheumatoid factor is an antibody found in varying levels in many RA patients. In the abovementioned study, patients with higher rheumatoid factor levels showed a better response to rituximab than did patients with lower levels.

This review concludes that there is a need for better comparisons between treatments, as well as methods for determining which patients would benefit most, when deciding which therapy to try after the failure of the first biologic DMARD.