There are five different tumor necrosis factor (TNF) inhibitors available for the treatment of RA. Researchers say that despite showing similar efficacy, they differ in molecular structures and signaling disruption.
A study of biologic agents used to treat rheumatoid arthritis (RA) would provide clinicians much-needed information, according to the authors of a recent review of the existing literature. Authored by Carla Bastida of the Pharmacy Department at the Hospital Clinic Barcelona, in Barcelona, Spain, and colleagues, the reviewers considered the many biologics that are currently being used to treat patients with RA.
RA treatment generally begins with non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and either chemical or synthetic disease-modifying anti-rheumatic drugs (DMARDs). When treatment with DMARDs does not work, biologic agents are used. As the scientific community has learned more about the pathogenesis of RA, new biologic agents have been developed and employed. The majority of biologic agents are monoclonal antibodies (mAbs).
There are five different tumor necrosis factor (TNF) inhibitors available for the treatment of RA: etanercept, infliximab, adalimumab, certolizumab, and golimumab. The reviewers say that “Despite clinical trials showing similar efficacy, they are not equivalent in terms of pharmacodynamics due to different molecular structures and signaling disruption.” They suggest this is one reason patients respond differently to the various anti-TNF agents.
The method the therapies are administered also seems to play a role, which the reviewers say implies a difference in pharmacokinetic profiles. Other biologic agents have been approved for treatment of RA, as well, including rituximab, abatacept, and tocilizumab. Each was originally approved for other conditions, then found to be efficacious in the treatment of RA.
There are safety concerns in the use of biologic agents, as there are with all pharmacological treatments. For instance, there seems to be some evidence that biologics interfere with the normal functioning of the immune system, increasing the risk of infections such as tuberculosis. Cost is another concern, as is the loss of efficacy due to anti-drug antibody (ADA) production. However, the reviewers say more studies are needed to understand biologics and ADA production in RA patients.
The reviewers suggest that therapeutic drug monitoring (TDM) may be the best way to learn more about how to best optimize the use of biologics to treat RA. There is debate among those in the research community, however, with some having concerns that TDM could increase the cost of biologics even further, as well as the claim that the large studies that have already been conducted in the approval process are sufficient.
The reviewers conclude that, because several RA treatment strategies include biologic agents, “the study of factors and covariates that could relevantly influence serum drug concentrations and exposure would be extremely useful”. They add that such studies would also help identify the most cost efficient methods of treatment. The full study, “Is there potential for Therapeutic Drug Monitoring of Biologic Agents in Rheumatoid Arthritis?” has been approved for publication in the journal British Journal of Clinical Pharmacology and was accompanied by a press release.