Lisa Stamp1, Melanie B Morillon2, William J Taylor3, Nicola Dalbeth4, Jasvinder A Singh5, Marissa Lassere6, Robin Christensen7. 1. Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch, New Zealand. Electronic address: lisa.stamp@cdhb.health.nz. 2. Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Rheumatology, Odense University Hospital, Denmark; Department of Medicine, Vejle Hospital, Denmark. 3. Department of Medicine, University of Otago, Wellington, New Zealand. 4. Department of Medicine, University of Auckland, New Zealand. 5. Department of Medicine, University of Alabama at Birmingham & Birmingham Veterans Affairs Medical Center, Birmingham, Alabama. 6. Department of Rheumatology, St George Hospital, University of NSW, Sydney, Australia. 7. Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Abstract
OBJECTIVES: The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials. METHODS: Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers. RESULTS: Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU. CONCLUSIONS: Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data-including longer duration extension studies-SU < 6mg/dL was associated with reduced gout flares.
OBJECTIVES: The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials. METHODS: Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers. RESULTS: Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU. CONCLUSIONS: Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data-including longer duration extension studies-SU < 6mg/dL was associated with reduced gout flares.
Authors: Till Uhlig; Lars F Karoliussen; Joe Sexton; Tore K Kvien; Espen A Haavardsholm; Fernando Perez-Ruiz; Hilde Berner Hammer Journal: Arthritis Res Ther Date: 2022-04-20 Impact factor: 5.606
Authors: Xiaomei Xue; Xuan Yuan; Lin Han; Xinde Li; Tony R Merriman; Lingling Cui; Zhen Liu; Wenyan Sun; Can Wang; Fei Yan; Yuwei He; Aichang Ji; Jie Lu; Changgui Li Journal: Front Med (Lausanne) Date: 2022-01-17