One size drug does not fit all: genetics and non-adherence

February 2018

Adherence to treatment balances on patients’ beliefs about the necessity for medication and their concerns about taking it (Necessity-Concerns Framework, NCF™). To support patients effectively there is a need to personalise. Each person’s experience of a medicine is particular to them and this experience is a key part of how they view that medicine. As the technical aspects of medicines continue to develop, this experience does not need to be left entirely to a ‘suck it and see’ approach. Let us take an example from genetics.

Variability in patients’ genetic characteristics can affect how patients respond to treatment. This variability can come in terms of enhancing their tolerance or resistance to a medicine, or altering their susceptibility to side effects. Genetic variation can, therefore, change behaviour towards medication especially when a patient’s perceived necessity and concerns deviate from the expected when they are given a standard dose. This jeopardises the patient’s motivation to take the medication as prescribed.

Control trials may not account for genetic differences in their participants’ selection process, usually recommending a one-size-fit-all type of dose [1]. Prescribing the same dose to all patients puts these patients at risk of non-adherence. If the patient experiences more side effects than somebody else on the same dose (concerns), or if the dose does not work (necessity). These change the perceptions a patient originally has about a medication.

For example:

CYP2C9 is an enzyme that metabolises warfarin to clear it from the body; since people with genetic polymorphisms of CYP2C9 are at double the risk of bleeding [2], this subgroup of patients, as they experience bleeding, will have increased concerns about their medication.

Genetic variability modifies the neurotransmission pathways, which affect the perception and sensitivity to pain (e.g. for migraine and cancer patients) [3]. This reminds us that treatment responses to analgesics will be patient-dependent and patients will need different amounts of medication for a given pain, potentially increasing side effects, lowering perceived efficacy and, in turn, the patient’s concerns towards their medication. In these cases, precision prescribing, by tailoring the dosage to a specific patient, may result in better adherence.

Pharmacogenetic testing may support medication adherence by increasing the patients’ understanding and confidence about their treatment. Studies have suggested that knowing you are being tested reduces anxiety about the treatments’ consequences, while discussing genetics with patients can increase patient-clinician communications and create a sense of control for patients who then share decisions with their doctor [4], positively contributing to adherence.

Currently, studies associating pharmacogenetics with health outcomes are scarce. Adherence programmes for therapy areas where it has been demonstrated genetic differences matter need to include tailoring the interventions to effectively support patients with these genetic polymorphisms.

[1] Frueh FW. Back to the future: why randomized controlled trials cannot be the answer to pharmacogenomics and personalized medicine. Pharmacogenomics. 2009;10:1077-1081. [2] Sanderson S, Emery J, Higgins J. 2005. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A HuGEnet™ systematic review and meta-analysis. Genet Med. 2005;7:97-104. [3] Zorina-Lichtenwalter K,

Meloto C.B., Khoury S., Diatchenko L. Genetic predictors of human chronic pain conditions. Neuroscience. 2016; 338:36-62. [4] Haga SB, La Pointe NMA. The potential impact of pharmacogenetic testing on medication adherence. Pharmacogenomics J. 2013;13:481–483.