- 1.Challenges in the Management of Chronic Gout James
Cheng-Chung Wei, M.D., Ph.D. Chief, Division of Allergy, Immunology
and Rheumatology Director, Chinese Medicine Clinical Trial Center
Associate professor, Institute of Medicine Chung Shan Medical
University Hospital
2. Challenges in the Management of Chronic GoutOutlines 1.
Patients -- Lack of awareness & poor compliance 2. Unmet
medical needs 3. Doctors -- Poorly follow the treatment guideline
3. Pathogenesis of Hyperuricemia in CKD & CVDKang DH, Nakagawa
T. Uric acid and chronic renal disease: possible implication of
hyperuricemia on progression of renal disease. Semin Nephrol
2005;25:43-49. 4. Treating Hyperuricemia and Preventing Disease
Progression Goals Achieve appropriate urate levels (< 6mg/dL)
without drug toxicity Therapy should be lifelong Intermittent
therapy or withdrawal of agents lead to recurrence of acute
attacks, tophi, CKDetc 5. Target Serum Urate Levels Not Always
Achieved Only 53% of patients on allopurinol achieved sUA goal of
< 6mg/dL (300 mg/day) Gout patients already taking allopurionl
assessed Average serum urate of 8.58 mg/dL in 66% (38/57) of
patients Average doses 100-300 mg/day 1. 2.Pereaz-Ruiz et al. Ann
Rheum Dis. 1998; 57:545-549 Li-Yu et al. J Rheumatol
2001;28(3):577-580 6. Very Low Drug Adherence Rate for Urate
Lowering Agents* Briesacher et al. Pharmacotherapy 2008 7. Why Are
Gout Patients Non-Adherent? Incompletely instructed Frequently have
other comorbidities Unmet medical needs Adverse drug events Lack of
efficacy1. 2. 3.Becker MA et al. N Eng J Med. 2005;353:2450-2461
Riedel AA et a. J Rheumtol. 2004;31:1575-1581 Dalbeth et al. BMC
Musculoskeletal Disorders 2012, 13:174 8. Challenges in the
Management of Chronic GoutOutlines 1. Patients -- Lack of awareness
& compliance 2. Unmet medical needs of drugs efficacy, esp.
CKD, tophi Drugs safety, esp. allergy, liver diseases3. Doctors --
Poorly follow the treatment guideline 9. Allopurinol Xanthine
oxidase inhibitor 100~300 HLA-B580160 ; Allopurinol 10. Allopurinol
(1) (tophaceous gout) (2) (24 800mg) (3) (4) (5) 2013 11.
Allopurinol Hypersensitivity 27 3 108 12. (Uricosuric agent)
Benzbromarone Probenecid Sulfinpyrazone (90%) 13. Benzbromarone
Benzbromarone 50150 (1) (2) sulfinpyrazoneprobenecidCcr30 ml/min
(3) 2013 14. Benzbromarone and the risk of nephrolithiasis Adverse
reaction in 20 out of 200 patients over a 10 year period1 Adverse
reactionPercentagediarrhoea73.5Allergy10.5Urinary sand41.5Renal
colic21.0Urate lithiasis41.5Oxalate lithiasis31.5Phosphae lithiasis
From benzbromarone package insertIncidence10.51. Masbernard A. et
al, 1981 Sa Medical Journal 9(1981): 701-706 15. Limitations with
Conventional ULT AllopuinolUricosuricsRenal function an
issueMultiple drug interactions *Target serum urate not always
achieved *Potentially fatal hypersensitivity syndromePotentially
fatal liver toxicityRisk of nephrolithiasis* probenecid 16. Renal
Impairment Veterans Affairs medical database: 47% of gouty
arthritis with CKD 2007-2008 Health and Nutrition Examination
Survey: 20% had nephrolithiasis Uricosuric agents: NOT recommended
in pts with CCR < 30 mi/min Poor efficacy, May increase risk for
urothiliasis Allopurinol: Decreased dose of allopurinol may limit
efficacy; Serious hypersensitivity reactions in CKD patients 17.
New Weapon for Chronic Gout Feburic Product Profile 18. Febuxostat
is Superior to Allopurinol for Achieving Target Serum UA level1.
Becker MA, Schumacher HR et al. Arthritis Res Ther 2010; 12(2): R63
2. Schumacher HR, Jr, Becker MA et al. Arthritis Rheum 2008;
59(11): 1540-1548 3. Becker MA , Schumacher HR, Jr et al. N Engl J
Med 2005; 353(23): 2450-2461 19. Febuxostat in Subjects with Mild
(CKD 2) and Moderate (CKD3) Renal Impairment Proportion of Subjects
With Serum Uric Acid 8.01. 2. 3. ( 6 mg/dL)2013 26. BNHI
Reimbursement IndicationReimbursement Allopurinol: 2.11. Antigout
agents Benzbromarone: Febuxostat: 2.11.1 Febuxostat(Feburic)
(101/4/1) 1.allopurinol benzbromarone 6.0 mg/dL 2. benzbromarone
allopurinol 27. My personal opinionUric acid lowering therapy
Uricosuric agents if no CCR700Allopurinol if no ADR history
HLA-B5801Febuxostate 28. : sUA < 6 mg/dL Febuxostat(101/4/1)A+B:
Allopurinol(A)Benzbromarone(B): sUA > 6mg/dL / 29. Challenges in
the Management of Chronic GoutConclusions 1. Need to improve
patients awareness & compliance 2. Dont forget the treatment
goal: Achieve lifelong appropriate urate levels (< 6mg/dL)
without drug toxicity3. Need to follow reasonable management
guideline