ArticleBritish journal of clinical pharmacology2018
Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Evaluation of urate-lowering therapy in hyperuricemia patients: a systematic review and Bayesian network meta-analysis of randomized controlled trials.Clinical rheumatology · 2020Pooled it
- A Pharmacometric Workflow for Resolving Model Instability in Model Use-Reuse Settings.CPT: pharmacometrics & systems pharmacology · 2025Article
- The Therapeutic Management of Chemical and Herbal Medications on Uric Acid Levels and Gout: Modern and Traditional Wisdom.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Non-Adherence in Adult Male Patients with Community-Acquired Pneumonia: Relative Forgiveness of Amoxicillin versus Respiratory Fluoroquinolones.Antibiotics (Basel, Switzerland) · 2023Article
- A semi-mechanistic exposure-response model to assess the effects of verinurad, a potent URAT1 inhibitor, on serum and urine uric acid in patients with hyperuricemia-associated diseases.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Combining Model-Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design.CPT: pharmacometrics & systems pharmacology · 2021Article
- Correction.British journal of clinical pharmacology · 2019Article
- A Six Sigma framework to successfully manage medication adherence.British journal of clinical pharmacology · 2019Article
- Effects of febuxostat on serum cytokines IL-1, IL-4, IL-6, IL-8, TNF-α and COX-2.Experimental and therapeutic medicine · 2019Article
- Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care.Clinical and translational science · 2018Review
- Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout.British journal of clinical pharmacology · 2018Article
- The Dual Role of Uric Acid: Pathological Implications Across Chronic Diseases and Current Approaches to Hyperuricemia Management.Discoveries (Craiova, Romania)Review
Corrections and comments
- Erratum issuedCorrection.2019
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
aimsDual-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.
methodsThe 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.
resultsSimulation 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.
conclusionsSuboptimal 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.