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To assume the association among suboptimal drug adherence and effectiveness and to assess the risk of hyperuricosuria among individuals with gout taking mono- and dual-ULTs.
Gout is one of the chronic painful disorder, which is difficult to
treat and effects a large number of people. Adherence to Dual-urate-lowering
therapy (ULT).
To assume the association among suboptimal drug adherence
and effectiveness and to assess the risk of hyperuricosuria among individuals
with gout taking mono- and dual-ULTs.
The two-compartment pharmacokinetic (PK) models and a
semi-mechanistic four-compartment pharmacodynamic (PD) model were applied to
investigate the impact of poor medication adherence. The PKPD model was applied
to evaluate mono and dual-ULT within gout patients with either overproduction
or under-excretion (lowered clearance) of uric acid, with suboptimal adherence
modelled as either doses are taken at random or a single drug holiday of rising
duration.
Simulation outcomes revealed a surge in urinary uric acid
appearing when dosing is resume after the missed doses. For under-excreters
administrating with a 20-day drug holiday, the supplement of 200 mg Lesinurad
to 80 mg Febuxostat raised the percentage of subjects feeling hyperuricosuria
from 0% to 1.4%. In overproducers, resuming ULTs after the drug holidays of
more than five days’ reaches to over 60% of subjects undergoing
hyperuricosuria.
Suboptimal medicine adherence may compromise the mono-
and dual-ULTs efficacy and safety, particularly among participants with gout
emerging from an overproduction of uric acid. Doctors and pharmacists should
acknowledge counselling individuals concerning the risks linked with partial
adherence, and suggest interventions to enhance adherence or tailor strategies,
where relevant.
Br J Clin Pharmacol. 2018 Jan;84(1):142-152.
Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout.
Hill-McManus D et al.
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