5 years ago

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

Elena Soto, Steven Lane, Dyfrig Hughes, Scott Marshall, Daniel Hill-McManus
Aims Dual-urate lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosurics can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of this study were to simulate the relation between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono and dual-ULTs. Methods The impact of poor medication adherence was studied using 2-compartment PK models based on published evidence and a semi-mechanistic, 4-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. Results 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 form 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. Conclusions Sub-optimal medication adherence may compromise 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bcp.13427

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