title: Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.
abstract: BACKGROUND
  Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies.
  
  
  OBJECTIVE
  To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD.
  
  
  METHODS
  A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings.
  
  
  RESULTS
  Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients.
  
  
  CONCLUSIONS
  Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur.
  
  
  BACKGROUND
  No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.
authors.affiliation: 1 Medical Director, Mid-America Region, naviHealth, Chicago, Illinois.
authors.forename: Ghaith
authors.initials: G
authors.lastname: Mitri
authors.affiliation: 2 Principal Health Outcomes Liaison, Daiichi Sankyo, Parsipanny, New Jersey.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wittbrodt
authors.affiliation: 3 Director and Head, U.S. Health Economics and Outcomes Research, Medical Affairs, Takeda Pharmaceuticals U.S.A., Deerfield, Illinois.
authors.forename: Robin S
authors.initials: RS
authors.lastname: Turpin
authors.affiliation: 4 Research Associate, Outcomes Research Solutions, Shrewsbury, Massachusetts.
authors.forename: Beni A
authors.initials: BA
authors.lastname: Tidwell
authors.affiliation: 5 Research Scientist and Principal, Outcomes Research Solutions, Shrewsbury, Massachusetts.
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Schulman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000191:economics / Q000627:therapeutic use*; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D000069465:Febuxostat / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D006073:Gout / Q000188:drug therapy* / Q000191:economics; D006074:Gout Suppressants / Q000191:economics / Q000627:therapeutic use*; D017048:Health Care Costs; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000191:economics / Q000503:physiopathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014527:Uric Acid / Q000378:metabolism
chemical_list: D006074:Gout Suppressants; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol