Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout

Hill-McManus, Daniel, Soto, Elena, Marshall, Scott, Lane, Steven and Hughes, Dyfrig ORCID: 0000-0001-8247-7459 (2018) Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 84 (1). pp. 142-152.

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Abstract

<h4>Aims</h4>Dual-urate-lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosuric agents can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono- and dual-ULTs.<h4>Methods</h4>The impact of poor medication adherence was studied using two-compartment pharmacokinetic (PK) models based on published evidence, and a semi-mechanistic four-compartment pharmacodynamic (PD) model. The PKPD model was used to simulate mono and dual-ULT in gout patients with either under-excretion (lowered clearance) or overproduction of uric acid, with suboptimal adherence modelled as either a single drug holiday of increasing duration or doses taken at random.<h4>Results</h4>Simulation results showed a surge in urinary uric acid occurring when dosing is restarted following missed doses. For under-excreters taking a 20-day drug holiday, the addition of 200 mg (or 400 mg) lesinurad to 80 mg febuxostat increased the percentage of patients experiencing hyperuricosuria from 0% to 1.4% (or 3.1%). In overproducers, restarting ULTs following drug holidays of more than 5 days leads to over 60% of patients experiencing hyperuricosuria.<h4>Conclusions</h4>Suboptimal medication adherence may compromise the safety and efficacy of mono- and dual-ULTs, especially in patients with gout resulting from an overproduction of uric acid. Clinicians and pharmacists should consider counselling patients with respect to the risks associated with partial adherence, and offer interventions to improve adherence or tailor treatments, where appropriate.

Item Type:	Article
Uncontrolled Keywords:	febuxostat, hyperuricosuria, lesinurad, pharmacodynamics, pharmacokinetics, urate-lowering therapy
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	09 Jun 2021 09:51
Last Modified:	19 Jan 2023 06:54
DOI:	10.1111/bcp.13427
Open Access URL:	https://research.bangor.ac.uk/portal/en/researchou...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3009571