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

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.