Tuesday, 28 February 2017 15:37

Fighting Adverse Drug Reactions

When it comes to therapeutic treatments, one size doesn’t fit all. Could genomic tests be the key to minimising the harmful side effects of drugs?

Adverse drug reactions (ADRs) are a fact of life. Notwithstanding the touchstone of medical ethics - primum non nocere, first, do no harm - medical interventions of any kind may cause undesirable side effects, albeit often outweighed by the health benefits. While ADRs are a significant cause of admissions to hospital (typically estimated at 6-7%), they occur at even higher rates within hospitals. It has been estimated that up to 70% of these harmful reactions are avoidable, and the considerable scope for improvement is of great interest to medics and scientists.

An emerging role for genomics

Tests for genetic variants associated with susceptibility or resistance to warfarin are already being used to guide prescription, enabling healthcare professionals to identify a safe and effective dose for each patient much more speedily than before. Can a similar method be used to help prevent ADRs more widely? 

Researchers at Alder Hey Children's Hospital have developed a new tool to assess how avoidable particular ADRs are, in the hope that the results can be used to plan preventative strategies. Research Pharmacist Dr Louise Bracken explained that an effective personalised medicine service is the long term goal, and said that the advancement of pharmacogenomics, which aims to optimise the use of medicines by tailoring prescription and dosage to an individual’s genes, is the way forward. 

The power of integrated data 

Health care providers in other countries, such as the Canadian Vancouver Clinic, have begun to combine information from electronic health record systems with clinician decision support services that incorporate genomic information. This integration can, for example, alert healthcare professionals to an individual’s risk of a particular reaction to a drug, as well as advising on appropriate dosages. 

Such systems need not necessarily be confined to hospitals; recent research in the US showed that combining information from genomic testing with clinical support tools out in the community, for patients with comorbidities and multiple medications, could reduce hospital readmissions by over 50% and visits to the emergency department by over 40%. The same study found that pharmacogenomics testing in patients at high risk of ADRs could reduce both costs and the risk of death. 

Preventing the worst first 

Even in the absence of electronic patient records and widespread pharmacogenomic testing, genomic information could help to identify those at risk of the most serious adverse reactions. Though vomiting and diarrhoea are unpleasant, they are not on the same scale as, for example, liver damage, which is potentially fatal – and around one in every ten cases of acute liver failure in the UK is caused by medication. Researchers in Nottingham have uncovered a rare variant of an immune system gene (HLA-A*33:01) that causes excessive immune reactions to a variety of common medications that result in liver damage. 

Other immune system genetic variants can be similarly significant; the HLA-B*1502 variant, for example, strongly predisposes patients to toxic epidermal necrolysis from the use of carbamazepine, whilst the HLA-B*5701 variant is associated with hypersensitivity to abacavir, a common treatment for HIV infection. With the advent of digital health records, and perhaps more affordable point-of-care tests, genomics could help progress towards a safer and more personalised future for patients.