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Matching medication to DNA leads to 30% fewer side effects

DNA abstract illustration

According to an international group of researchers including a team from the University of Liverpool, patients experience 30% fewer side effects when medication doses are tailored to their DNA.

The group’s study, published in The Lancet, is the first to demonstrate the practical application of using a panel of genes to tailor drug prescription to the individual.

The ‘one-size-fits all’ approach for prescribing medication as currently used leads to problems with the effectiveness and safety of medicines. Due to variations in our genetic information, patients may respond differently to a specific drug – for example, some individuals process medication faster than others and, as a result, require a higher dose to achieve the necessary effect. Others process it slower, which can lead to side effects.  To facilitate this, the researchers developed a ‘DNA medication pass’ that associates a patient’s genetic profile to drugs whose processing is influenced by DNA. Scanning the pass enables doctors and pharmacists to know what the optimal medication is, and its dose, for the individual being treated.

Standard vs adjusted dose

The Lancet study found that patients who actively make use of the medication pass, and whose drugs and doses are adjusted according to their DNA, experienced 30% fewer serious side effects than patients who were prescribed a standard dose of medication. Approximately 7000 patients from seven European countries were assessed over several medical specialities, including oncology, cardiology, psychiatry and general medicine.

In participants who were randomised to the genotyping arm, their DNA was mapped. Researchers then looked at 12 specific genes. 50 types of genetic variants were shown to affect how the 39 selected drugs worked. Up to 12 weeks after initiating treatment, patients were contacted by a nurse specialist who enquired about their side effects, such as diarrhoea, anaemia, nerve pain or muscle pain.

Not only did patients holding the DNA medication pass experience fewer side effects, they also expressed great satisfaction with the pass itself. According to the researchers, the pass gives patients the feeling of being more in control, as they become actively involved in their personalised treatment.

Only UK study site

Liverpool was the only UK site to take part in this multi-national randomised study, recruiting 1037 patients from the Royal Liverpool University Hospital and from two GP surgeries. Researchers at the University of Liverpool worked with the co-ordinator in obtaining funding from the EU Commission, and also assisted with the design of the trial – including the use of the Liverpool Causality Assessment Tool in assessing causality of the adverse reactions, which was important for determining the primary outcome measure used in the study.

Professor Sir Munir Pirmohamed, who was the UK principal investigator, and chaired the committee that published the personalised prescribing report, said: “This is a large landmark randomised study which shows that pharmacogenomic testing using a comprehensive genotyping panel can prevent adverse drug reactions, an outcome measure which is clinically important to individual patients and to healthcare systems.  A 30% reduction in adverse reactions with a single intervention is remarkable.  This is also consistent with the Personalised Prescribing report that was published by the Royal College of Physicians and British Pharmacological Society, which called for the implementation of pharmacogenomics into the NHS.”

Could the DNA medication pass become part of standard care?

The study was coordinated by Henk-Jan Guchelaar, Professor of Clinical Pharmacy at Leiden University Medical Center. He has conducted research in the field of pharmacogenetics for over 20 years. “For the first time we have proven that a ‘tailored’ strategy works at a large scale within clinical practice. There is now enough evidence for us to proceed with implementation,” says Guchelaar.

Figuring out the subsequent stages of the implementation process also raises various questions which will be different in each country.  In the UK, the steps for implementing pharmacogenomic testing in the NHS have been outlined in the Personalised Prescribing report.  Guchelaar notes. “By adapting implementation to suit each country’s healthcare system, we can make treatment more effective and safer for millions of patients”.

This study was funded by a European Commission Horizon 2020 programme grant.

The U-PGx consortium was led by Leiden University Medical Center and consists of: Uppsala Universitet, University of Liverpool, Karolinska Institutet, Biologis, KNMP, UMC Utrecht, Golden Helix Foundation, Institut für Klinische Pharmakologie in Stuttgart, Centro di Riferimento Oncologico Aviano, Medizinische Universität Wien, University of Patras, Junta de Andalucía, Université de Toulouse, Universitätsklinikum Aachen, Univerza v Ljubljani.

Click here to access the full study. 

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