Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial.

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified sub cohort analysis of a randomized controlled trial. SETTING: & Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1) and maintained during weeks 25-48 (Phase 2). Gout flare was assessed between weeks 49-72 (Phase 3). OUTCOME: Gout flare between weeks 49-72 (Phase 3) was the primary outcome. Secondary outcomes included sUA goal achievement and ULT dosing at end of Phase 2, and serious adverse events (SAEs). ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: 351 of 940 participants (37.3%) had CKD; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; p=0.02) despite similar attainment of sUA goal (79% vs. 81%; p=0.6) by the end of Phase 2. Acute kidney injury (AKI) was more common in participants with stage 3 CKD randomized to allopurinol compared to febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen.

Knowledge of and Stated Adherence to the 2020 ACR Guideline for Gout Management: Results of a Survey of US Rheumatologists.

OBJECTIVE: This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout. METHODS: A 57-item questionnaire was administered to a sample of US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations. RESULTS: All 201 rheumatologists approached completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum 15), whereas the mean overall stated agreement score was 7.7 (maximum 14). Less experienced rheumatologists (≤ 8 yrs; n = 49) were likely to claim adherence to more individual ACR recommendations than those with more experience (> 8 yrs; n = 152; mean stated adherence score: 12.3 vs 11.3; P ≤ 0.05). Rheumatologists who claimed to see ≤ 75 patients with gout in 6 months (n = 66) had a mean stated adherence score of 12.1 vs 11.2 for those who claimed to have seen > 75 patients (P ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat: 43%; allopurinol: 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares. CONCLUSION: The self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.

Patient Experience with Chronic Refractory Gout and Its Impact on Health-Related Quality of Life: Literature Review and Qualitative Analysis.

INTRODUCTION: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL). METHODS: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population. RESULTS: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants. CONCLUSIONS: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

Skeletal muscle mass and quality in gout patients versus non-gout controls: A computed tomography imaging study.

OBJECTIVE: Patients with gout are at elevated risk of multiple vascular and metabolic comorbidities. Whether they are also at risk of sarcopenia, which is known to affect patients with other rheumatic diseases, has not been previously assessed. We examined whether patients with gout have decreased lumbar muscle quality and quantity, indicating an association between gout and sarcopenia. METHODS: Fifty gout subjects and 25 controls, ages 45-80, underwent computed tomography imaging of the lumbosacral spine. We measured muscle quantity (skeletal muscle area [SMA] and index [SMI]) and quality (skeletal muscle radiation attenuation [SMRA] and intermuscular adipose tissue [IMAT] area and index [IMATI]) of the psoas and erector spinae muscles at the L3 level. RESULTS: Seventy subjects (45 gout and 25 controls) were included in the analysis. Gout subjects had higher BMI, more kidney disease and hypertension, lower exercise frequency, and higher mean serum urate and creatinine vs. controls. Lumbar SMRA was significantly lower in gout subjects vs. controls, indicating reduced muscle quality. Lumbar IMAT area was significantly higher in gout subjects vs. controls, as was lumbar IMATI, indicating increased muscle adiposity. These differences persisted after adjusting for potential confounders. In contrast, there was no significant difference between gout and control groups in lumbar SMA or lumbar SMI, suggesting that muscle quantity may not be routinely affected by the diagnosis of gout. CONCLUSIONS: Gout patients exhibit decreased lumbar muscle quality compared with controls, consistent with an association between gout and sarcopenia.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

OBJECTIVE: Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. METHODS: This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. RESULTS: Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. CONCLUSION: These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

2020 American College of Rheumatology Guideline for the Management of Gout

To provide guidance for the management of gout, including indications for and optimal use of urate- lowering therapy (ULT), treatment of gout ares, and lifestyle and other medication recommendation Fifty- seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta- analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the nal recommendations and grade their strength as strong or conditional.Results. Forty- two recommendations (including 16 strong recommendations) were generated. Strong recommen-dations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout ares; allopurinol as the preferred rst- line ULT, including for those with moderate- to- severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat- to- target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinammatory prophylaxis therapy for a duration of at least 3­6 months was strongly recommended. For management of gout ares, colchicine, nonsteroidal antiinammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.Conclusion. Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.