Pain Reporter: Adalimumab Study Author Explains Its New Mechanism of Action

A recent Daily Dose brought to light a University College London study documenting the additional benefits of adalimumab, an anti-inflammatory medication. Michael Ehrenstein, PhD, ­­­­­­­is a Consultant Rheumatologist at UCL Hospitals and coauthor of this study. He answered a few questions for the Pain Reporter.

Q. Why did you and your team initiate this study?

A. We wanted to understand the effects of TNF on regulatory T cells in patients, given that the literature was contradictory. Using data from both human and mouse studies, some investigators found that TNF impaired regulatory T cell function, whilst others found the opposite. Our data implied that TNF impaired Treg function, which was the natural assumption given that when patients were treated with anti-TNF therapy their regulatory T cell function was enhanced. However, our data shows that adalimumab rather than block membrane TNF actually enhances its interaction with TNF receptor 2 expressed on regulatory T cells and boosts their function.

Q. Inflammation seems to be the culprit for so many conditions/diseases. Do you plan to study its effects on different patient groups?

A. We have looked only at patients with rheumatoid and healthy controls using an in vitro assay. We did not see an effect in healthy controls and therefore I doubt whether it would help diseases where inflammation and TNF have not been proven to play a role. We plan to look at the effects of adalimumab in diseases where this treatment has been shown to work such as Crohn’s or psoriatic arthritis.

Q. How does adalimumab help TNF to form anti-inflammatory cells?

A. Adalimumab binds to TNF on the surface of monocytes and increases its expression. In addition, adalimumab enhances the interaction between membrane (surface) TNF and its receptor on regulatory T cells, which boosts their function.

Q. What is the next step in your trials? What other disease would you like to see included in the studies?

A. We are also working on an assay that could predict response to adalimumab therapy in patients with rheumatoid arthritis. This could avoid adalimumab therapy in patients not likely to respond with all the cost saving and health benefits for patients.

Read more about adalimumab here.



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