Publish Date: 17.02.2023

Category: News from the University

UL sodelovala v prelomni raziskaviAvtor fotografije: Sangharsh Lohakare (Unsplash)

The research findings of an international group from seven countries, headed by researchers from Leiden University Medical Centre (LUMC), and involving the participation of researchers from the Faculty of Medicine of the University of Ljubljana, show that patients experience as much as 30% fewer serious adverse side effects of medication if the choice of medicines is adapted to their genetic code. The study, which was published in medical journal The Lancet, is the first to demonstrate the advantages of prescribing medication from various therapeutic groups based on the genetic code of the individual patient.

The research published in The Lancet established that among patients whose dosage of medication was adapted to their genetic code, there was a 30% lower incidence of serious adverse side effects than among patients who took the standard doses of medication. The research involved around 7,000 patients from seven European countries with various health conditions including cardio-vascular diseases, various forms of cancer, mental and other illnesses.

“The University of Ljubljana is proud that our researchers participated in extremely important research on the advantages of determining the genetic code of patients before prescribing medications. We have known for some time that people respond in different ways to different medications, and taking a large sample of patients with various conditions, this research has shown that we can in fact improve the safety of treatment by adapting the medication to the individual’s genetic picture. This serves to greatly reduce the occurrence of adverse side effects of medicines. Although determining genetic code is relatively expensive, prescribing medications in this more targeted way translates in the long term into savings for the healthcare system, since the reduced consumption of medication in this new approach to prescriptions would result in direct savings for the healthcare budget, and indirectly would generate greater savings due to the lower incidence of adverse side effects. This means fewer visits to the doctor, less frequent changing of medication and better effects of treatment,” notes Prof. Dr Gregor Majdič, Rector of the University of Ljubljana, speaking about the importance of the research.

Research includes 716 Slovenian patients

In addition to researchers from the Laboratory of Pharmacogenetics at the Faculty of Medicine of the University of Ljubljana, the research included 716 Slovenian patients and involved more than 50 physicians and health workers from 11 different health centres and clinics. The research group in Slovenia was headed by Prof. Dr. Vita Dolžan, head of the Institute of Biochemistry and Molecular Genetics at the Faculty of Medicine.

“Pharmacogenetics represents an important part of personalised medicine, which aims through molecular genetic approaches to improve diagnostics, the prognosis of the disease and the effectiveness of treatment for the individual patient depending on their genetic make-up. Through pharmacogenetic testing we can identify patients for whom the metabolisation of medications changes due to genetic variability. Through what is termed a pre-emptive approach, even before the start of treatment we can apply genetic testing to predict the response to medication, and especially to the increased risk of adverse side effects in the individual patient,” she explains.

Participants were invited to join the research when they began taking one of the medications whose metabolisation can be affected by genetic factors. In all patients they tested for the presence of 50 different changes in the code of 12 specific genes that can affect the efficacy of 39 selected medications. For the patients in the study group, genetic analysis was performed before or upon the start of treatment, and for patients in the control group the genetic analysis was performed at the end of the research. In a period of 12 weeks after the start of treatment, nurses or researchers regularly surveyed the participating patients and checked for the occurrence of adverse side effects of medications, such as diarrhoea, nausea, headache, vertigo, pain, loss of taste and similar. Patients who have taken doses of medications adapted to their genetic code reported fewer adverse side effects, while at the same time they were very pleased with the pharmacogenetic card and the results they obtained. In the opinion of the researchers, a pharmacogenetic card gives patients the feeling that they are actively included in their treatment.

The next step? Adapting medication using genetic codes for anyone

The international research was conducted under the leadership of Henk-Jan Guchelaar, professor of clinical pharmacology at LUMC, who has spent more than 20 years researching in the field of pharmacogenetics. “We proved for the first time that an adapted approach works for a large number of medications. Now we have available sufficient evidence for us to be able to continue its use in clinical practice,” says Guchelaar. “This means that the next step is to start using dosages of medication adapted to genetic code,” adds Jesse Swen, a hospital pharmacist and the head researcher.

On determining the next stages of the transfer of these findings into practice, a range of questions arise for the researchers: Should the costs of pharmacogenetic testing for adapted medication doses be refunded? Should this become a part of standard care? Guchelaar and Swen take the view that this should be the case. In their opinion, the research provides a good basis for this. “We want pharmacogenetic testing to the accessible for every patient that needs medication,” stresses Guchelaar. “In this way we can ensure more effective and safer treatment for each patient.”

The research was financed through funds from the European Commission Horizon 2020 programme (no. 668353).

The U-PGx consortium was headed by the LUMC hospital and comprises the following institutions: 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, University of Ljubljana.

Photo: example of a card received by Slovenian patients included in the research.

The statements of some of the physicians, health workers and patients involved in the research are posted here.

The video statement made by Prof. Dr Vita Dolžan for STA is available here.

As part of the UPGx project a 6-minute video (in English) was recorded with an explanation of the pharmacogenetic ID card, and there is also a shorter, 3-minute version. Both are available at this link.