Pharmacogenomic testing could help reduce adverse drug reactions in the UK

A new study from Queen Mary University of London found that 9% of all reported adverse drug reactions (ADRs) reported to the UK medicines regulator are associated with medications where side effect risk is partly dependent on patient's genes. Of this subset of ADRs, 75% were associated with only three genes that impact how the body processes medication. Genetic testing before prescribing could therefore help avoid ADRs in these cases. 

Over the past 60 years, The Medicines and Healthcare products Regulatory Agency (MHRA)'s Yellow Card scheme recorded over one million reports of side effects – also known as adverse drug reactions (ADRs) – to medications. Previous studies have indicated that more than 99% of individuals have genetic variants which could lead to an adverse response to certain drugs. In some cases, these reactions can be serious and lead to further health problems, longer hospital stays, or even death. The cost of ADRs to the NHS is estimated to be more than £2 billion a year. 

A new study, published today in PLOS Medicine, led by Dr. Emma Magavern from Queen Mary University of London analysed over 1.3 million ADR reports submitted to the MHRA Yellow Card scheme. It found that 115,789 (9%) were associated with drugs for which side effect risk can be modified using pharmacogenomics (PGx) information to guide prescribing. Of these, 75% were associated with three genes that affect the way an individual processes medication (CYP2C19, CYP2D6, SLCO1B1). 

The type of medications that showed the highest volume of ADRs that could be prevented by personalising prescribing with genetic information were treatments for psychiatric disorders (47%) and cardiovascular problems (24%). The study also found that patients who had ADRs which were able to be mitigated by PGx were more likely to be male, older, and to experience side-effects that were severe but non-fatal. 

Clinical trials have shown that using genetic information to guide prescribing pre-emptively, such as adjusting the dose or choosing different medication, can avoid ADRs and improve patient outcomes. This research highlights the potential of integrating pharmacogenomic testing into clinical practice to make medicines safer and more effective for patients. 

Dr. Emma Magavern, NIHR Clinical Academic Lecturer in Queen Mary's Centre for Clinical Pharmacology and Precision Medicine who led the study, said: "It is important to understand the landscape of side effects reported nationally over the past half century to elucidate the impact that prospective use of genetic testing to personalise prescribing may have in the UK." 

Professor Sir Mark Caulfield, Vice-Principal (Health) at Queen Mary and co-author, said: "This is the largest analysis of the potential role of pharmacogenomics in adverse reactions from a national spontaneous reporting system. It suggests that 9% of these reports may relate to our genetic make-up. This could be avoidable if we had measured the genetic make-up of the person before prescribing these medicines. It is time for the NHS to consider adopting pre-emptive testing for known genes that interact with medications." 

This study shows how reports of suspected side effects to the Yellow Card scheme can help us better understand and prevent serious side effects, including those linked to genetic factors. The MHRA Yellow Card scheme collects reports of suspected side effects from patients, the public and healthcare professionals and plays an important role in monitoring the safety of medicines in the UK. This research also reinforces the importance of our pioneering Yellow Card Biobank with Genomics England, which will help us take a more personalised, proactive approach to patient safety and make medicines safer for everyone." 

June Raine, MHRA Chief Executive