2014 GSS Updates on Gout

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2014 GSS Updates on Gout

  1. 1. UPDATES ON GOUT TREATMENT SIDNEY ERWIN MANAHAN, MD, FPCP, FPRA Internal Medicine – Rheumatology 31 January 2014
  2. 2. “The INTERNIST is expected to diagnose and initiate treatment, continue treatment or refer for problems and specialized treatment” GOUTY ARTHRITIS Glossary of Disease and Disorders in General IM Practice, Philippine College of Physicians, 2011
  3. 3. 25 in 100 will have hyperuricemia 1 in 100 will have gouty arthritis 50 of 100 gout patients have complications Salido EO, et al. PJIM 2008; 46: 273-6. Manahan L, et al Rheum Int 1985. Dans LF, et al J Rheum 1997. Dans LF, et al. PJIM 2006. Roberto LC, et al. Poster. PRA 2007
  4. 4. Phases of Gout and Treatment Goals Asymptomatic Hyperuricemia Prevent gouty arthritis ACUTE GOUT Terminate flare INTERVAL GOUT CHRONIC GOUT Prevent repeated flares Reverse / prevent complications
  5. 5. Serum Uric Acid (SUA) and Incident Gout 5 year Incidence of Gout 80% 61.1% 60% 40% 27.7% 20% 10.8% 0.0% 0% <6.0 7.0-7.9 8.0-8.9 Serum Uric Acid (mg/dl) Roddy and Doherty, Arthritis Research & therapy 2010; 12: 23 >9.0
  6. 6. How to treat Asymptomatic Hyperuricemia?
  7. 7. Dietary Prescriptions for Gout and HU AVOID LIMIT ENCOURAGE • Organ meats • Seafoods • Dairy Products • Drinks with fructose (corn syrup) • Sweetened fruit juices • Vegetables • Alcohol overuse (esp if with attack of gout) Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 ACR Guidelines for Management of Gout. Part 1. Arth Care & Res 2012; 64 (10): 1431-46.
  8. 8. Is Pain VAS >7/10? Yes TREATING ACUTE GOUT Start COMBINATION therapy No Start MONOTHERAPY Is there ADEQUATE* response? Yes Complete therapy No * Improvenent >20% in 24hr or >50% after 24 hr REVIEW Diagnosis; REVISE therapy Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
  9. 9. Treating Acute Gout COMBINATION 3 IA Steroid AND Any of the three COLCHICINE NSAIDs STEROIDS 1.0 mg then 0.5 mg TID 12 hours later FULL antiinflammatory dose Prednisone 0.5 mkd for 5-10 days Triamcinolone 60 mg IM COMBINATION 1 ACTH 25-40 IU SC x 1-2 doses COMBINATION 2 Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
  10. 10. Treating Acute Gout COLCHICINE NSAIDs Chronic Kidney Disease St 3-5   Peptic Ulcer Disease   Heart Failure or Anticoagulants  Diabetes or Infection Liver Disease STEROIDS     Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
  11. 11. Preventing Flares COLCHICINE NSAIDs STEROIDS 0.5 mg OD-BID Low doses + PPI Naproxen 250 mg BID Pred <10mg/d DURATION WHICH EVER IS LONGER • 6 months • 3 months of achieving target SUA if with no visible tophi • 6 months of achieving target SUA and resolution of visible tophi Khanna D, Khanna PP, Fitzgerald JD, et al. 2012 ACR Guidelines for Management of Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
  12. 12. Lowering Serum Uric Acid (SUA) <6mg/dl <5mg/dl For patients without tophi For patients with tophi
  13. 13. When to Start Urate Lowering Therapies (ULT) • At least 2 flares/year • Presence of tophi • Radiographic changes of gouty arthropathy • Nephrolithiases • Co-morbid conditions that may complicate treatment of gout (CV disease, CKD)
  14. 14. Choosing Among Urate Lowering Therapies (ULTs) URICOSURICS XANTHINE OXIDASE INHIBITORS URICASE Probenecid Sulfinpyrazone Allopurinol Febuxostat Pegloticase Losartan Fenofibrates Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 ACR Guidelines for Management of Gout. Part 1. Arth Care & Res 2012; 64 (10): 1431-46.
  15. 15. Febuxostat 40 mg/d Allopurinol 100mg/d Check if target SUA is achieved 40 mg q 2-4 weeks 100mg q 2-4 weeks Develops adverse event / not tolerated Shift to Allopurinol Shift to Febuxostat Target SUA not achieved on max doses Add uricosuric agent or consider pegloticase
  16. 16. ALLOPURINOL Non-selective purine FEBUXOSTAT Selective Non-purine WHICH IS BETTER?
  17. 17. FACT (2005) Becker MA, Schumacher HR, et al. NEJM 2005; 353 (23): 2450-61 APEX (2008) Schumacher HR, Becker MA, et al. Arth Rheum 2008; 59(11): 1540-8 FOCUS (2009) Schumacher HR, Becker MA, et al. Rheum 2009; 48: 188-94 EXCEL (2009) Becker MA, Schumacher HR, et al. J Rheum 2009; 36 (6): 1273-82 CONFIRMS (2010) Becker MA, Schumacher HR, et al. Arth Res Ther 2010; 12 (2): R63 Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  18. 18. End Points at Febuxostat 40mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* Gout flares 40 41 0.97 (0.57 to 1.65) 1324 (1) SUA<6mg% 432 408 1.1 (0.94 to 1.20) 1324 (1) Serious AE 25 41 0.61 (0.35 to 1.07) 1513 (1) Withdrawal 104 85 1.2 (0.90 to 1.70) 1513 (1) * 300 mg if normal renal function, 200 mg if impaired renal function Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  19. 19. Safety at Febuxostat 40mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* LFT AbN 83 110 0.76 (0.53 to 1.08) 1513 (1) Skin reaction 58 73 0.80 (0.54 to 1.17) 1513 (1) CV Events 50 60 0.84 (0.55 to 1.28) 1513 (1) HPN 0 0 0 1513 (1) 567 573 0.99 (0.91 to 1.08) 1513 (1) TOTAL AE * 300 mg if normal renal function, 200 mg if impaired renal function Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  20. 20. End Points at Febuxostat 80mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* Gout flares 228 204 1.1 (0.98 to 1.30) 2325 (3) SUA<6mg% 716 398 1.8 (1.60 to 2.10) 2193 (3) Serious AE 39 45 0.88 (0.55 to 1.42) 1044 (3) Withdrawal 265 202 1.3 (1.14 to 1.51) 1044 (3) * 300 mg if normal renal function, 200 mg if impaired renal function Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  21. 21. Withdrawals at Febuxostat 80mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* Adv Events 74 71 1.05 (0.80 to 1.39) 1044 (3) Gout flare 23 9 2.99 (0.70 to 12.79) 1044 (3) Efficacy 5 2 3.08 (0.55 to 17.20) 1044 (3) Others 242 194 1.25 (0.90 to 1.74) 1044 (3) TOTAL 265 202 1.3 (1.14 to 1.51) 1044 (3) * 300 mg if normal renal function, 200 mg if impaired renal function Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  22. 22. Safety at Febuxostat 80mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* LFT AbN 61 60 1.03 (0.76 to 1.39) 1044 (3) Skin reaction 45 57 0.78 (0.56 to 1.09) 1044 (3) CV Events 34 36 ** 0 (-0.02 to 0.01) 1044 (3) HPN 10 1 4.35 (1.25 to 15.09) 1044 (3) TOTAL AE 591 664 0,94 (0.89 to 0.99) 1044 (3) * 300 mg if normal renal function, 200 mg if impaired renal function ** Risk difference Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  23. 23. End Points at Febuxostat 120mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* Gout flares 542 420 1.3 (0.87 to 1.90) 986 (2) SUA<6mg% 829 384 2.2 (1.90 to 2.50) 880 (2) Serious AE 58 50 1.16 (0.70 to 1.93) 1513 (1) Withdrawal 321 236 1.4 (1.12 to 1.66) 1041 (3) * 300 mg if normal renal function, 200 mg if impaired renal function Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  24. 24. Withdrawals at Febuxostat 120mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* Adv Events 75 50 1.57 (0.49 to 5.03) 1041 (3) Gout flare 65 19 3.42 (1.72 to 6.81) 1041 (3) Efficacy 6 2 ** 0 (0.00 to 0.01) 1041 (3) Others 186 165 1.13 (0.87 to 1.47) 1041 (3) TOTAL 321 236 1.36 (1.12 to 1.66) 1041 (3) * 300 mg if normal renal function, 200 mg if impaired renal function ** Risk difference Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  25. 25. Safety at Febuxostat 120mg Outcome Risks (/1000) Relative Risk (95% CI) Population (#Studies) Febuxostat Allopurinol* LFT AbN 44 50 0.89 (0.51 to 1.53) 1513 (1) Skin reaction 35 35 1.00 (0.53 to 1.89) 1513 (1) CV Events 10 2 ** 0.01 (0.00 to 0.02) 1513 (1) HPN 12 6 ** 0.01 (-0.01 to 0.02) 1513 (1) TOTAL AE 715 797 0.90 (0.84 to 0.96) 1513 (1) * 300 mg if normal renal function, 200 mg if impaired renal function ** Risk difference Tayar JH, Lopez-Olivio MA, Suarez-Almazor ME. Febuxostat for treating chronic gout. Cochrane Database of Sys Rev 2012; 11: Art No CD008653
  26. 26. Why Choose One Over the Other?
  27. 27. Dosing Efficacy of Allopurinol Zhang W et al Ann Rheum Dis 2006; 65: 1312-1324 EULAR Evidence Based Recommendations for Gout
  28. 28. SUA Trend in Theoretical Patient Serum Uric Acid levels (mg/dl) 10 8 Allopurinol* 6 Allopurinol Febuxostat 4 2 0 2 4 6 8 10 12 Duration of treatment (Weeks) 14 16
  29. 29. SUMMARY • Treat gout at different stages of the disease • Discussed differences in the efficacy and safety of available xanthine oxidase inhibitors
  30. 30. Survey of Practices in Gout Therapy Treating ACUTE GOUT 12% 67% Preventing gout FLARES 77% INDICATIONS for urate lowering therapy 6% DURATION of urate lowering therapies 5% Hamijoyo L, et al. Unpublished 2007.
  31. 31. LET’S IMPROVE OUTCOMES IN GOUT! This potential for cure with adequate long-term treatment makes gout a rewarding condition for clinicians to manage. Perez Ruiz F. Treating to target: a strategy to cure gout. Rheumatology 2009; 48 (supp 2):ii9-ii14.
  32. 32. It will cover the pathogenesis, environment/ genetics, diagnostics, management and prevention of various rheumatic conditions. Visit us at http://www.aplarcongress.org http://www.facebook.com/aplar2014

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