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Adherence and Outcomes with Urate-Lowering Therapy: A Site-Randomized Trial

Published:November 29, 2018DOI:https://doi.org/10.1016/j.amjmed.2018.11.011

      Abstract

      Purpose

      The purpose of this study was to test a pharmacist-led intervention to improve gout treatment adherence and outcomes.

      Methods

      We conducted a site-randomized trial (n=1463 patients) comparing a 1-year, pharmacist-led intervention to usual care in patients with gout initiating allopurinol. The intervention was delivered primarily through automated telephone technology. Co-primary outcomes were the proportion of patients adherent (proportion of days covered ≥0.8) and achieving a serum urate <6.0 mg/dl at 1 year. Outcomes were reassessed at year 2.

      Results

      Patients who underwent intervention were more likely than patients of usual care to be adherent (50% vs 37%; odds ratio [OR] 1.68; 95% confidence interval [CI] 1.30, 2.17) and reach serum urate goal (30% vs 15%; OR 2.37; 95% CI 1.83, 3.05). In the second year (1 year after the intervention ended), differences were attenuated, remaining significant for urate goal but not for adherence. The intervention was associated with a 6%-16% lower gout flare rate during year 2, but the differences did not reach statistical significance.

      Conclusions

      A pharmacist-led intervention incorporating automated telephone technology improved adherence and serum urate goal in patients with gout initiating allopurinol. Although this light-touch, low-tech intervention was efficacious, additional efforts are needed to enhance patient engagement in gout management and ultimately to improve outcomes.

      Keywords

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      References

        • Zhu Y
        • Pandya BJ
        • Choi HK
        Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008.
        Arthritis Rheum. 2011; 63: 3136-3141
        • Choi HK
        • Curhan G
        Independent impact of gout on mortality and risk for coronary heart disease.
        Circulation. 2007; 116: 894-900
        • Garg R
        • Sayles HR
        • Yu F
        • et al.
        Gout-related health care utilization in US emergency departments, 2006 through 2008.
        Arthritis Care Res. 2013; 65: 571-577
        • Kleinman NL
        • Brook RA
        • Patel PA
        • et al.
        The impact of gout on work absence and productivity.
        Value Health. 2007; 10: 231-237
        • Singh JA
        • Strand V
        Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilisation in US veterans.
        Ann Rheum Dis. 2008; 67: 1310-1316
        • Mikuls TR
        Urate-lowering therapy.
        in: Firestein GS Budd RC Gabriel SB McInnes IB O'Dell JR 10th ed. Kelley & Firestein's Textbook of Rheumatology. Vol I. 10th ed.. Elsevier, Philadelphia, PA2017: 1061-1074
        • Agematsu K
        • Nagumo H
        • Yang FC
        • et al.
        B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production.
        Eur J Immunol. 1997; 27: 2073-2079
        • Briesacher BA
        • Andrade SE
        • Fouayzi H
        • Chan KA
        Comparison of drug adherence rates among patients with seven different medical conditions.
        Pharmacotherapy. 2008; 28: 437-443
        • Cottrell E
        • Crabtree V
        • Edwards JJ
        • Roddy E
        Improvement in the management of gout is vital and overdue: an audit from a UK primary care medical practice.
        BMC Fam Pract. 2013; 14: 170
        • Rashid N
        • Coburn BW
        • Wu YL
        • et al.
        Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system.
        J Rheumatol. 2015; 42: 504-512
        • Roddy E
        • Zhang W
        • Doherty M
        Concordance of the management of chronic gout in a UK primary-care population with the EULAR gout recommendations.
        Ann Rheum Dis. 2007; 66: 1311-1315
        • Singh JA
        • Hodges JS
        • Asch SM
        Opportunities for improving medication use and monitoring in gout.
        Ann Rheum Dis. 2009; 68: 1265-1270
        • Solomon DH
        • Avorn J
        • Levin R
        • Brookhart MA
        Uric acid lowering therapy: prescribing patterns in a large cohort of older adults.
        Ann Rheum Dis. 2008; 67: 609-613
        • Khanna D
        • Fitzgerald JD
        • Khanna PP
        • et al.
        2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia.
        Arthritis Care Res (Hoboken). 2012; 64: 1431-1446
        • Richette P
        • Doherty M
        • Pascual E
        • et al.
        2016 updated EULAR evidence-based recommendations for the management of gout.
        Ann Rheum Dis. 2017; 76: 29-42
        • Wortmann RL
        • Macdonald PA
        • Hunt B
        • Jackson RL
        Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials.
        Clin Ther. 2010; 32: 2386-2397
        • Dalbeth N
        • House ME
        • Horne A
        • Petrie KJ
        • McQueen FM
        • Taylor WJ
        Prescription and dosing of urate-lowering therapy, rather than patient behaviours, are the key modifiable factors associated with targeting serum urate in gout.
        BMC Musculoskelet Disord. 2012; 13: 174
        • Stamp LK
        • Merriman TR
        • Barclay ML
        • et al.
        Impaired response or insufficient dosage? Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout.
        Semin Arthritis Rheum. 2014; 44: 170-174
        • Coburn BW
        • Michaud K
        • Bergman DA
        • Mikuls TR
        Allopurinol dose escalation and mortality among patients with gout: A national propensity-matched cohort study.
        Arthritis Rheumatol. 2018;
        • Coburn BW
        • Cheetham TC
        • Rashid N
        • et al.
        Rationale and design of the randomized evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study.
        Contemp Clin Trials. 2016; 50: 106-115
        • Koebnick C
        • Langer-Gould AM
        • Gould MK
        • et al.
        Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.
        Perm J. 2012; 16: 37-41
        • Oake N
        • Jennings A
        • van Walraven C
        • Forster AJ
        Interactive voice response systems for improving delivery of ambulatory care.
        Am J Manag Care. 2009; 15: 383-391
      1. Nau DP. Proportion of Days Covered (PDC) as a preferred method of measuring medication adherence. Available at: http://pqaalliance.org/resources/adherence.asp. Accessed April 25, 2018.

        • Halpern R
        • Fuldeore MJ
        • Mody RR
        • Patel PA
        • Mikuls TR
        The effect of serum urate on gout flares and their associated costs: an administrative claims analysis.
        J Clin Rheumatol. 2009; 15: 3-7
        • Doherty M
        • Jansen TL
        • Nuki G
        • et al.
        Gout: why is this curable disease so seldom cured?.
        Ann Rheum Dis. 2012; 71: 1765-1770
        • Perez-Ruiz F
        Treating to target: a strategy to cure gout.
        Rheumatology (Oxford). 2009; 48: ii9-ii14
        • Coburn BW
        • Mikuls TR
        The problem with gout is that it's still such a problem.
        J Rheumatol. 2016; 43: 1453-1455
        • Zhang W
        • Doherty M
        • Bardin T
        • et al.
        EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).
        Ann Rheum Dis. 2006; 65: 1312-1324
        • Becker MA
        • Schumacher HR, Jr.
        • Wortmann RL
        • et al.
        Febuxostat compared with allopurinol in patients with hyperuricemia and gout.
        N Engl J Med. 2005; 353: 2450-2461
        • Schumacher HR, Jr.
        • Becker MA
        • Wortmann RL
        • et al.
        Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.
        Arthritis Rheum. 2008; 59: 1540-1548
        • Coburn BW
        • Bendlin KA
        • Sayles H
        • Meza J
        • Russell CL
        • Mikuls TR
        Allopurinol medication adherence as a mediator of optimal outcomes in gout management.
        J Clin Rheumatol. 2017; 23: 317-323
        • Rees F
        • Jenkins W
        • Doherty M
        Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study.
        Ann Rheum Dis. 2013; 72: 826-830
        • Abhishek A
        • Jenkins W
        • La-Crette J
        • Fernandes G
        • Doherty M
        Long-term persistence and adherence on urate-lowering treatment can be maintained in primary care-5-year follow-up of a proof-of-concept study.
        Rheumatology (Oxford). 2017; 56: 529-533
        • Counsell AB
        • Nguyen AD
        • Baysari MT
        • Kannangara DRW
        • McLachlan AJ
        • Day RO
        Exploring current and potential roles of Australian community pharmacists in gout management: a qualitative study.
        BMC Fam Pract. 2018; 19: 54
        • Fields TR
        • Rifaat A
        • Yee AMF
        • et al.
        Pilot study of a multidisciplinary gout patient education and monitoring program.
        Semin Arthritis Rheum. 2017; 46: 601-608
        • Goldfien R
        • Pressman A
        • Jacobson A
        • Ng M
        • Avins A
        A pharmacist-staffed, virtual gout management clinic for achieving target serum uric acid levels: a randomized clinical trial.
        Perm J. 2016; 20: 18-23
        • Qaseem A
        • Harris RP
        • Forciea MA
        clinical guidelines committee of the American College of P. Management of Acute and Recurrent Gout: a clinical practice guideline from the American College of Physicians.
        Ann Intern Med. 2017; 166: 58-68
        • Schumacher Jr., HR
        • Becker MA
        • Lloyd E
        • MacDonald PA
        • Lademacher C
        Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study.
        Rheumatology (Oxford). 2009; 48: 188-194
        • Kim SC
        • Newcomb C
        • Margolis D
        • Roy J
        • Hennessy S
        Severe cutaneous reactions requiring hospitalization in allopurinol initiators: a population-based cohort study.
        Arthritis Care Res (Hoboken). 2013; 65: 578-584
        • Yang CY
        • Chen CH
        • Deng ST
        • et al.
        Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan.
        JAMA Intern Med. 2015; 175: 1550-1557
        • Stamp LK
        • Taylor WJ
        • Jones PB
        • et al.
        Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol.
        Arthritis Rheum. 2012; 64: 2529-2536