Practical Diagnosis of Gout

1. Practical Diagnosis of Gout

2. Caveat on urate levels • Serum uric acid level may be normal at the time of an acute attack. • Normal level does not rule out gout. • May be better to recheck the level after 2 weeks

3. Differential Diagnosis of Gout

4. Treatment of Gout

5. Gout Management Approach

6. Resolve the acute flare rapidly • NSAIDs • Corticosteroids • Colchicine Remember that above may all be limited by comorbidities !! Antiinflammatories do not treat the underlying disease.

7. Summary of EULAR Recommendations: Treatment

8. Summary of EULAR Recommendations: Treatment

9. The Role of Dietary and Lifestyle Recommendations

10. Initiate Urate-Lowering Therapy

11. Use Concomitant Anti-Inflammatory Prophylaxis

12. Evidence for the Use of Concomitant Anti-Inflammatory Prophylaxis

13. Evidence Supporting ContinuousLowering of Serum Urate to <6 mg/dL

14. Reduction in Recurrent Gout Flares When sUA Levels Are Maintained at <6 mg/dL

15. Benefits of Long-TermUrate-Lowering Therapy

16. Conclusions Long term approach

18. Allopurinol • Purine “backbone” xanthine oxidase inhibitor • FDA approved in 1966, most widely used urate-lowering drug for the last four decades. • Basis for the 1988 Nobel Prize in Physiology and Medicine. • Starting dose of 50-100mg daily and slowly titrate; consider prophylaxis against flare. • Some studies suggested that only 21% of patients on 300mg achieved urate level < 6.0.

19. New and Emerging Gout Meds • febuxostat– oral nonpurine xanthine oxidase inhibitor FDA approved in 2009 for gout and hyperuricemia • pegloticase – PEGylated uricase; not yet FDA approved-- for advanced tophaceous gout, administered intravenously.

20. Febuxostat • FDA approved doses are 40mg and 80mg. • Published RCT looked at higher doses as well. • Compared to allopurinol, was as good or superior in achieving goal of sUA <6.0. • Significant reduction in gout flares and tophi when sUA goal is maintained.

21. ULORIC A Allopurinol has a purine backbone. Febuxostat is a non-purine xanthine oxidase inhibitor. Febuxostat

22. Febuxostat • Primarily excreted by the liver, only 3% by the kidney; no dosage reduction required for renal impairment. • Mild transaminase elevations observed, similar to that of allopurinol. • Contraindicated with use of 6-MP, azathioprine, theophylline • In RCT a higher rate of CV and thromboembolic events noted (0.14 / 100 pt-years > allopurinol), but a causal relationship not identified

23. Febuxostat • Primarily excreted by the liver, only 3% by the kidney; no dosage reduction required for renal impairment. • Mild transaminase elevations observed, similar to that of allopurinol. • Contraindicated with use of 6-MP, azathioprine, theophylline • In RCT a higher rate of CV and thromboembolic events noted (0.14 / 100 pt-years > allopurinol), but a causal relationship not identified

24. Febuxostat • In general 40mg (starting dose) not inferior to 300mg allopurinol. 80 mg dose produced higher rate of achieving target sUA level of <6.0 and reduction of flares • 5-year findings (FOCUS) showed sustained effect with maintenance of sUA < 6.0 and nearly complete suppression of flares

25. References (febuxostat) • Becker, M.A., et al. NEJM.353:2450, December 8, 2005 {“FACT trial”} • Schumacher, H.R., et al. Rheum. 48; (2),188- 194. {“FOCUS” 5-year findings} • Becker, M.A, et al. Arthr & Rheum, 52; (3), 916-923. • Schumacher, H.R., et al. A&R (Arthr Care & Research). 59; (11), 1540-1548.

26. Thank you !!