Drug interactions reducing immunotherapy efficacy

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Steroids, proton-pump inhibitors and antibiotics may play a part in reducing the effectiveness of a new class of cancer immunotherapy.

The interaction between pharmaceuticals plays a really important role in the clinical management of certain conditions. The efficacy and sometimes extreme side effects of strong drugs used for cancer management can vary wildly depending on drug combinations. This is due to the pharmacodynamic (PD) and pharmacokinetic (PK) interactions that change factors such as absorption, distribution, metabolism and elimination of each drug. As you might expect, we do not yet know how every drug interacts with another, but this is an important area of research.

The recent discovery of immune checkpoint inhibitors (ICIs) has opened a new wave of research into how they react with other drugs, as they work in a different way by activation of T-cell responses against cancer. While we have some understanding of which drugs do affect the properties, new research is seeking to weigh drugs against each other to better elucidate the effect of other medications on ICIs.

Dr David Pinato, alongside a number of researchers from research institutions in Italy, have set about a retrospective observational study to weigh medications against each other and see what could be most useful in improving the efficacy of these ICIs. The team looked at patients under the care of 20 Italian institutions receiving ICIs for stage IV cancer alongside being prescribed a selection of other medications such as statins, steroids, proton-pump inhibitors, anti-coagulants, non-steroidal anti-inflammatory drugs and many others, for a pre-existing condition. The team made sure to also look at the underlying reasons for why people were prescribed other medication to rule out other conditions playing a role.

Though these are still preliminary results that does not discriminate the link is mechanistic or associative, it was found that steroids, often given as a baseline for cancer patients, antibiotics and proton pump inhibitors have a negative effect on the ICIs. This means they are having a negative impact on the effectiveness of these drugs.

This research is a steppingstone towards understanding these interactions, and the team are planning to look at prospectively collected data to elucidate interactions between concomitant baseline medications and immunotherapy clinical outcomes.

Infrastructure support was provided to Dr Pinato by the NIHR Imperial Biomedical Centre.

Photo by Olga DeLawrence on Unsplash