An investigation of remission in patients with gout – efficacy of treatments, prediction of remission and outcomes

Lead Investigator: Nicola Dalbeth, University of Auckland
Title of Proposal Research: An investigation of remission in patients with gout – efficacy of treatments, prediction of remission and outcomes
Vivli Data Request: 8874
Funding Source: None
Potential Conflicts of Interest: Nicola Dalbeth has received consulting fees, speaker fees or grants from AstraZeneca, Novartis, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma outside the proposed work. The proposed work will be undertaken as part of her academic role at the University of Auckland, and has not been funded by any commercial source.

Summary of the Proposed Research:

Gout is a chronic disease caused by the deposition of monosodium urate (MSU) crystals within joints. Formation of these crystals results from elevated serum urate levels in the blood. The deposit of the MSU crystals causes intermittent gout flares (severe pain and swelling), chronic gouty arthritis, and the formation of tophi (clusters of crystals visible under the skin). In Aotearoa New Zealand, the prevalence of gout is highest amongst Māori and Pacific peoples who are more likely to be admitted to hospital compared to non-Māori and non-Pacific New Zealanders. Amongst Māori and Pacific peoples, it is estimated that 8.5% and 14.8% respectively are affected by gout compared to 4.7% of New Zealand European people Gout is a is debilitating disease that diminishes the health-related quality of life of those affected, and as such remission is an important goal of treatment.

In chronic rheumatic diseases, such as gout, the state of remission can be defined as “either a complete absence of disease activity or a level of disease activity so low that it is not troublesome to the patient and portends a later good prognosis”. In 2016, a preliminary gout remission criteria was developed, defined as the following: absence of gout flares, absence of tophi, serum urate less than 0.36mmol/L, pain due to gout <2 on a 0-10 scale and patient global assessment of gout disease <2 on a 0-10 scale. It was agreed that these outcomes should be sustained over a 12-month period to define remission. We also propose a simplified gout remission criteria consisting of the following 3 domains: (1) Absence of gout flares (2) Absence of tophi (3) serum urate of less than 0.36mmol/L.

There has been support for the validity and use of the proposed remission criteria. However, it is not known whether the proposed remission criteria can predict future improved outcomes such as radiographic damage (changes to the joint structures visible through imaging such as x-rays), improvement in physical activity, and development of other health conditions (health related quality of life). Other factors such as the baseline (pre-treatment) factors that predict remission and the best treatment strategies that lead to remission, are also unknown.

There have been substantial clinical trials investigating people with gout on different interventions across a time period of 12 months or longer. Within these trials, researchers also collect baseline (pre-treatment) clinical data as well as outcomes post treatment. By analyzing the data from these clinical trials and conducting meta-analyses, we can determine the most effective interventions for remission, the baseline variables that predict achievement of remission and whether being in remission leads to improved health outcomes. We want to analyze these already available clinical studies as they can provide necessary outcomes needed to measure remission.

Our study will guide gout management by providing a holistic treatment goal- remission- which extends beyond a single outcome. In addition, this will allow researchers conducting clinical trials to measure disease control more broadly thus providing a method of assessing and reporting true disease suppression

Requested Studies:

A Multicenter, Randomized, Active-Control, Phase 3B Study to Evaluate the Cardiovascular Safety of Febuxostat and Allopurinol in Subjects With Gout and Cardiovascular Comorbidities
Data Contributor: Takeda
Study ID: NCT01101035
Sponsor ID: TMX-67_301

A Phase 3, Randomized, Multicenter Study Comparing the Safety and Efficacy of Oral Febuxostat Versus Allopurinol in Subjects With Gout
Data Contributor: Takeda
Study ID: NCT00102440
Sponsor ID: C02-010

A Phase 3, Open-Label, Randomized, Allopurinol-Controlled Study to Assess the Long-Term Safety of Oral Febuxostat in Subjects With Gout
Data Contributor: Takeda
Study ID: NCT00175019
Sponsor ID: C02-021

A Multicenter, Randomized, Double-Blind, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo in Joint Damage in Hyperuricemic Subjects With Early Gout
Data Contributor: Takeda
Study ID: NCT01078389
Sponsor ID: TMX-67_204

Phase II, Open-Label Study, to Assess the Long-Term Safety of Oral TMX-67 in Subjects With Gout
Data Contributor: Takeda
Study ID: NCT00174941
Sponsor ID: TMX-01-005