New DBI-EPIbreath^® test enables a better quality of life for patients living with epilepsy

For more details, read our whitepaper.

Epilepsy can be a challenging condition to manage; every patient responds differently to antiseizure medication (ASM), and side effects are common. Therapeutic drug monitoring (TDM) plays an important role in seizure control, measuring drug concentrations in a patient’s blood to follow their response to treatment. However, optimal systemic ASM concentrations do not always equate to improved clinical outcomes and minimal side effects. A more recent development is DBI-EPIbreath^®, a non-invasive, real-time breath analysis approach that acts as a complementary diagnostics tool for patient monitoring and stratification.

Choosing the right drug can be a lengthy process
Drug selection is heavily influenced by patients’ individual profiles; they may have dramatically different beneficial and adverse responses, and tolerances, to the same drug. Valproate is usually an excellent first choice for generalized epilepsy or when epilepsy types are not clear, with the exception of women at child-bearing age. It is usually administered at low dosage to begin with, increasing until seizures are controlled, or an unacceptable side effect occurs. If the drug proves unsuitable, the process is repeated with another ASM or drug combination. This continues until a solution is found that provides seizure control with minimal side effects. It can be a lengthy process and a frustrating experience, and may have to be repeated if the patient later relapses or becomes pharmaco-resistant.

The importance and limitations of traditional therapeutic drug monitoring
It is important to implement a treatment regimen as quickly as possible after diagnosis to ensure seizures are controlled in the shortest possible time frame. This requires not only a fast diagnosis, but also quick decision making in respect of ASM. TDM based on the measurement of the drug concentration in plasma or serum has a crucial role to play once a diagnosis has been made and treatment started. However, this approach does have limitations. Blood sampling is undesirable in children, as it can be distressing and it may be difficult to obtain sufficient sample volume. Adults, too, may find giving blood distressing, and even be phobic. In addition, it can take several days to receive the results. Some patients – such as non-responders or those suffering from unacceptable side effects – may need testing on a regular basis. This requires repeated blood draws, which is generally unpleasant and therefore can only be performed at a limited frequency. As a result, clinicians often find that they don’t have as much information as they would like to guide optimal drug treatment.

New complementary tool supports the decision-making process
Breath testing with DBI-EPIbreath^® is a complementary approach to traditional TDM, designed to assist in the management of ASM dosing regimens. It is the first non-invasive test for real-time measurement of the concentration and drug response of valproic acid to be CE certified under IVDD, and delivers results in just 10 minutes. DBI-EPIbreath^® combines secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) with sophisticated bioinformatic tools to enable a machine learning approach to molecular breath analysis. The result is a patient-friendly breath test that reliably estimates circulating concentrations of valproic acid. All the patient has to do is exhale into a SESI-HRMS instrument. The data is then analyzed using machine learning algorithms incorporated into DBI-EPIbreath^®, rapidly determining the total and free valproic acid values in blood. Alongside this, the test calculates a predicted likelihood – low, moderate or high – of drug response, as well as a side effects risk score. This helps clinicians identify whether a person is likely to benefit from the treatment and/or suffer from unwanted side effects.

Reaping the benefits
A big advantage of DBI-EPIbreath^® is that tests can be performed as often as necessary. Consequently, it is an ideal fast and non-invasive complementary tool to blood testing. This is a major benefit in pediatrics, where a blood draw can be challenging. There are also advantages if more frequent testing is required for any reason, for example, if a patient is non-responsive or develops pharmaco-resistance. In addition to determining valproic acid levels, a time series analysis provides an intuitive overview of drug dosage and response over a 12-month period, giving an indication of the patient’s stability and any trends occurring. Breath analysis by SESI-HRMS can also contribute to risk assessment, as it not only captures data relating to valproic acid and its metabolites, but also a large number of other metabolites. This provides extra information to help gauge the likelihood of non-response or side effects.

Looking to the future
While DBI-EPIbreath^® focuses on monitoring valproic acid in epilepsy, this is just the start. Research is ongoing to expand the use of SESI-HRMS and this machine learning approach to include TDM of other ASMs. There is also great potential to use molecular breath analysis to identify and exploit biomarkers for other conditions and disease areas in the future. This would mean that many more people could benefit from fast, non-invasive TDM. Furthermore, clinicians would have access to additional information to help determine treatment pathways.

It may also be possible to use an offline breath collector, allowing patients to provide a sample during attendance at a clinic, or even from the comfort of their own home. This would open up testing to people for whom real-time breath analysis is not feasible, such as those unable to attend the hospital test facility or pediatric patients. As the technique is applied to more applications, increasing numbers of patients with varying medical issues will benefit, which bodes well for the future.

For more details, read our whitepaper.