Photo: The Lancet
Patients can experience 30 per cent fewer serious adverse reactions if their drugs are tailored to their genes, reports a study published in The Lancet. A European collaboration involving researchers from Karolinska Institutet suggests that a genetic analysis prior to drug therapy could significantly reduce suffering and healthcare costs.
A significant proportion of patients experience adverse reactions to their medication. Since we each carry a unique set of genes, we react differently to the same drugs. For example, some people break them down faster, meaning that they require a higher dose to obtain the desired effect.
Magnus Ingelman-Sundberg.
Photo: Wendy van Hemmen-van Veelen
DNA pass fits in the wallet
To overcome this problem, researchers from Leiden University Medical Center in the Netherlands, Karolinska Institutet and other collaborating institutions have developed the principle for a “DNA pass” that has been clinically validated in the recently published study.
“It’s basically a credit card-sized card with a magnetic strip containing all the important genetic data on a particular patient,” explains one of the study’s co-authors, professor of molecular toxicology at the at Karolinska Institutet.
“When a patient’s card is scanned, doctors and pharmacists can work out the optimal dose of a drug for that particular individual.”
The study included almost 7,000 patients from seven European countries between March 2017 and June 2020 all of whom were genotyped with respect to variations in twelve specific genes of significance to drug metabolism, transport and side-effects. All participants then received their drugs either conventionally or with a genotype-based modification.
Twelve weeks after their drug regimen began, the patients were contacted by a specialist nurse about any adverse reactions, such as diarrhoea, pain or loss of taste. The study concluded that such adverse reactions to drugs can be greatly reduced by analysing the genes that code for enzymes that metabolise them.
“The patients who’d received genotype-driven treatment had, on average, 30 per cent fewer adverse reactions than the controls,” says Professor Ingelman-Sundberg.
Now sufficiently compelling data
Professor Ingelman-Sundberg, a long-standing expert at the European Medical Agency on the development of this method, believes that there is now sufficiently compelling data to warrant the widespread use of the DNA pass.
“I think we’ve come to the point where a genetic pass like this will be useful,” he says.
Globally, the problem of adverse reactions is considerable. In the EU, they cause up to 128,000 fatalities a year and up to nine per cent of all hospital admissions, a figure that more than doubles to 20 per cent in people over 70. Moreover, the costs of adverse reactions are heavy and in Sweden alone are estimated to amount to 12 or 15 billion kronor a year.
“Our results strongly suggest that an initial genotyping of the patients will deliver significant savings to society,” says Professor Ingelman-Sundberg. “The genotyping itself need only be done once per patient at a maximum cost of 6,000 SEK. The general introduction of this predictive system could therefore go a long way towards reducing public healthcare costs.”
The study was financed mainly by EU Horizon 2020 and led by researchers at the Leiden University Medical Center.
Publication
“A controlled prospective real-world implementation study of a 12-gene pharmacogenetic panel to prevent adverse drug reactions in 6,944 patients in seven European countries.” Jesse J Swen, Cathelijne H van der Wouden, Lisanne EN Manson, Heshu Abdullah-Koolmees, Kathrin Blagec, Tanja Blagus, Stefan Böhringer, Anne Cambon-Thomsen, Erika Cecchin, Ka-Chun Cheung, Vera HM Deneer, Mathilde Dupui, Magnus Ingelman-Sundberg, Siv Jonsson, Candace Joefield-Roka, Katja S Just, Mats O Karlsson, Lidija Konta, Rudolf Koopmann, Marjolein Kriek, Thorsten Lehr, Christina Mitropoulou, Emmanuelle Rial-Sebbag, Victoria Rollinson, Matthias Samwald, Elke Schaeffeler, Maria Skokou, Matthias Schwab, Daniela Steinberger, Julia C Stingl, Roman Tremmel, Richard M Turner, Mandy H van Rhenen, Cristina L Dávila Fajardo, Vita Dolžan, George P Patrinos, Munir Pirmohamed, Gere Sunder-Plassmann, Giuseppe Toffoli, Henk-Jan Guchelaar, The Lancet, online xx 2022, doi: xx
