1798: Health-Related Quality of Life Improvements Resulting from a Treat-to-Target Strategy in the Management of Gout: Post- Hoc Analysis of a Multicenter, Randomized, Double-Blind, Non-Inferiority Trial

Lindsay Helget¹, James O'Dell¹, Jeff Newcomb¹, Maria Androsenko², Mary Brophy², Anne Davis-Karim³, Bryant England¹, Ryan Ferguson², Michael Pillinger⁴, Tuhina Neogi⁵, Paul Palevsky⁶, Hongsheng Wu² and Ted Mikuls⁷, ¹University of Nebraska Medical Center, Omaha, NE, ²VA Boston Cooperative Studies Program Coordinating Center, Boston, MA, ³VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, ⁴NYU Grossman School of Medicine, New York, NY, ⁵Boston University School of Medicine, Boston, MA, ⁶University of Pittsburgh School of Medicine, Pittsburgh, Pittsburgh, ⁷Division of Rheumatology, University of Nebraska Medical Center, Omaha, NE

Background/Purpose: The ACR recommends a treat-to-target strategy in gout management, centered on the titration of urate lowering therapy (ULT) to a goal serum urate (SU) of < 6.0mg/dL. However, there is a paucity of data regarding improvements in health-related quality of life (HRQoL) when receiving a treat-to-target regimen for gout management. Using data from the recently completed multicenter, randomized, double-blind, STOP Gout Study (O'Dell JR et al. NEJM Evidence 2022), we examined changes in HRQoL accompanying ULT administered as part of a treat-to-target strategy.

Methods: Participants with gout and SU concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. ULT was titrated during weeks 0-24 (Phase 1) and maintained during weeks 25-48 (Phase 2), with escalation as necessary, to reach goal SU of < 6.0 mg/dL. Participants were observed on a stable ULT dose during weeks 49-72 (Phase 3). For this analysis, participants were considered non-responders to ULT (either allopurinol or febuxostat based on randomization) if they did not achieve a goal SU of < 6.0mg/dL in Phase 2 (mean levels at weeks 36, 42 and 48) despite maximal ULT dosing. The EQ-5D-3L and VR-12 (a Veteran's Administration HRQoL outcome based of the SF-12) questionnaires were collected and compared at baseline, 24 weeks, and 48 weeks and differences were examined over these time points using a repeated measures ANOVA. Baseline HRQoL values were compared by responder status using a t-test. Associations of SU change between baseline and 48 weeks, and SU goal achievement at 48 weeks with change in HRQoL outcomes were examined using linear regression models.

Results: Of the 940 trial participants, 764 had SU response data available at week 48 and were included in this analysis; 618 (80.9%) of these achieved a target SU goal < 6.0 mg/dl. Participants deemed non-responders at 48 weeks reported lower HRQoL scores at baseline when compared to responders (p< 0.001). Improvements in both measures were similar between allopurinol and febuxostat treatment arms (p >0.7 for both HRQoL measures). From baseline to 48 weeks both EQ-5D-3L and VR-12 questionnaire scores improved significantly in all participants (p< 0.0001) (Table 1). Neither SU change nor responder status (achievement of SU goal) at 48 weeks were associated with changes in HRQoL (Table 2).

Conclusion: In this secondary analysis from a large, randomized double-blind, non-inferiority trial comparing the efficacy and safety of allopurinol and febuxostat in the management of gout, we have found that HRQoL outcome measures improved with treat-to-target ULT. Over this period of observation, SU change achieved was not associated with HRQoL improvement, suggesting that a longer follow up period may be needed to identify these associations and/or that HRQoL improvements may be more closely tied with other gout outcomes such as recurrent flare. Regardless, these findings demonstrate that patients receiving treat-to-target ULT experience significant HRQoL gains even early in the course of management, supporting current ACR practice guidelines.
<img src=https://www.abstractscorecard.com/uploads/Tasks/upload/17574/QHOPTGBB-1290920-1-ANY.jpg width=440 height=247.5 border=0 style=border-style: none;>

Table 2. Associations of SU change from baseline to 48 weeks and Responder Status (SU goal achievement) with change in EQ-5D-3L and VR-12; estimates generated using linear regression analysis
*Covariates include age, race/ethnicity (white, African American, other), chronic kidney disease, hypertension, diabetes, cardiovascular disease, body mass index, baseline SU, and treatment assignment.

Disclosures: L. Helget, None; J. O'Dell, None; J. Newcomb, None; M. Androsenko, None; M. Brophy, None; A. Davis-Karim, None; B. England, Boehringer-Ingelheim; R. Ferguson, None; M. Pillinger, Horizon Therapeutics, Sobi, Fortress Bioscience, Hikma; T. Neogi, Novartis, Pfizer/Lilly, Regeneron; P. Palevsky, None; H. Wu, None; T. Mikuls, Gilead Sciences, Bristol-Myers Squibb, Horizon, Sanofi, Pfizer Inc.