2. Assumptions
“The ACR gout guidelines are designed
to emphasize safety and quality of
therapy and to reflect best practice.”
• Correct Diagnosis
• Consider Co-morbid conditions
• Evaluate for Drug interactions
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. 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.
3. Levels of Evidence
A Meta-analyses
>1 Randomized Clinical Trial
B Single Randomized Clinical Trial
Non-Randomized Studies
Standards of Care
C Case Studies
Expert Consensus
4. Nomenclature (Acute)
SEVERITY (Pain VAS)
1 2 3 4 5 6 7 8 9 10
DURATION (from onset of symptoms)
0 12 24 36
FREQUENCY (No of flares/ year)
1 2 3 4 5 6 7 8 9 10
5. Nomenclature
JOINT INVOLVEMENT
• Few small joints
• 1 or 2 large joints
• Polyarthritis
• 4 or more joints
involving >1 region
• 3 large joints
6. Nomenclature (CTG)
MILD MODERATE SEVERE
Affects 1 joint Affects 2-4 joints Simple tophi in >4 joints
Stable disease Stable disease OR
Simple tophi Simple tophi >1 Unstable tophus
7. Domains in Gout Care
• Acute Gout
• Prophylaxis
• Urate Lowering Therapy
• Chronic Tophaceous 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. 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. Treating Acute Gout
• Treat with pharmacologic therapy (C)
• Best started within 24 hours(C)
• Do not interrupt those on established urate-
lowering therapy (C)
• Educate patient on
– Initiating treatment when w/ a flare (B)
– Effective urate lowering being “curative” (B)
10. Choosing an Anti-Inflammatory
Start
Pain VAS Yes
<7/10
MONOTHERAPY
(A)
No
CONSIDER
Start
• Patient preference
COMBINATION
• Prior response to meds
THERAPY (C)
• Associated co-morbids
11. NSAIDs in Acute Gout
• Full anti-inflammatory dose/ acute pain
– Naproxen (A)
– Indomethacin (A)
– Sulindac (B)
– Other NSAIDs (B or C)
– Etoricoxib (A)
– High dose Celecoxib (B)
• Continue until flare completely resolves (C)
12. Colchicine in Acute Gout
• Best if given <36 hours of onset
• Dosing regimen
– 1.2 mg initially then 0.6 mg after 1 hour then 0.6 mg
BID until acute gout resolves (A)
– 1.0 mg initially then 0.5 mg after 1 hour then 0.5 mg
TID until acute gout resolves (C)
• Do not give IV
• Reduce in moderate-severe CKD
• Caution with clarithromycin, erythromycin,
cyclosporin and disulfiram
13. Steroids in Acute Gout
• Oral or IA steroids if 1-2 joints involved (B)
• IA steroid dose depends on joint size (B)
• Recommended dosing
– Prednisone 0.5 mkd for 5-10 days (A)
– Prednisone 0.5 mkd for 2-5 days then taper
for 7-10 days (C)
– Triamcinolone 60 mg IM with oral steroids (C)
– No consensus for ACTH (A)
14. Combination Therapy in Acute Gout
• Colchicine with NSAIDs
• Colchicine with Steroids
• IA Steroids with Colchicine/ NSAIDs/ Oral
Steroids
• Consider topical ice application (B)
15. Treating the Patient on NPO
• IA steroids for 1-2 large joints (B)
• IV or IM Methylprednisolone (or equivalent)
0.5 – 2.0 mkd (B)
• ACTH 25-40 IU SC (A)
• No consensus on IM Ketorolac or IM
Triamcinolone (C)
17. Continuing Acute Gout Care
INADEQUATE
RESPONSE REVIEW the diagnosis
Yes
<20% in 24H CONSIDER
or <50% after • Shift to other drug (C)
24H • Combine therapy (C)
No • Anakinra 100 mg SC for
3 days (B)
• Canakinumab 150 mg
COMPLETE SC single dose (A)
TREATMENT
19. Drugs for Prophylaxis
• First Line Drugs
– Colchicine 0.5 – 0.6 mg OD-BID (A)
– Naproxen 250 mg BID + PPI (C)
• Alternate Agents
– Prednisone <10mg/d (C)
• Lack of consensus on off-label anti-IL-1 (A)
20. Duration of Prophylaxis
Choose the greater of the following:
• 6 months duration (A)
• 3 months of achieving target BUA in patients
without tophi (B)
• 6 months of achieving target BUA AND
resolution of previously noted tophi on PE (C)
21. URATE LOWERING
THERAPY
Pharmacologic and Non-Pharmacologic
22. Diet and Lifestyle Changes
AVOID LIMIT ENCOURAGE
Organ meats (B) Seafood (B) Low fat or non-fat dairy
Drinks with fructose(C) Sweetened fruit juices (C) products (B)
Alcohol overuse (B) Sugar (C) Vegetables (C)
Alcohol during an acute Salt (C)
attack (C)
23. Evaluating Hyperuricemia (C)
• Educate the patient (B)
– Diet and lifestyle changes
– Disease, treatment and objectives
– Role of hyperuricemia and targets
• Consider eliminating non-essential meds that
increase serum uric acid (C)
• Evaluate for co-morbid conditions and
contributors to hyperuricemia (C)
• Assess gout disease burden
25. Indications for ULT
• Evidence of tophus/tophi (A)
• Frequent attacks (>2/year) (A)
• History of nephrolithiases (C)
• Chronic Kidney Disease Stage 2-5 (C)
26. Target Blood Uric Acid
<6 mg/dl <5 mg/dl
For most gout scenarios For more durable
(if without visible tophi) improvement and patients
(A) with visible tophi (B)
27. Urate Lowering Therapy
• First Line Agents (A)
– Allopurinol 100-800 mg/d
– Febuxostat 40-120 mg/d
• Alternative Therapy (B)
– Probenecid (except when Cr Cl <50ml/min and history
of urolithisases)
• Can be started during an attack(!) PROVIDED
effective anti-inflammatory therapy has been
given (C)
28. Allopurinol Dosing Guide
• Starting dose <100mg/d (B)
– For CKD 4-5, starting dose is 50mg/d (B)
• Titrate up every 2-5 weeks (C)
• Dose of >300mg/d can be used provided patient
is monitored for AHS and other AE (B)
– Pruritus, Rash, Inc LFT, Eosinophilia
29. Allopurinol Dosing Guide
Maximum Recommended
Allopurinol Dose Based on Crea
Clearance
Crea Cl (ml/min) Dose
0 100 mg q 3 days
10 100 mg q 2 days
20 100 mg/day
40 150 mg/day
60 200 mg/day
80 250 mg/day
100 300 mg/day
120 350 mg/day
30. Pharmacogenetics for AHS
Patients at high risk for AHS should consider
screening for HLA-B*5801 (A)
– Korean descent with CKD 3 or worse (A)
– Han Chinese
– Thai
31. Approach to ULT
• Titrate XOI to max recommended dose (A)
• If up-titration is not tolerated or target BUA is
not achieved, consider shift to other XOI (C)
• If target BUA is not achieved, start combination
therapy by adding a uricosuric (B)
• Last option, if still unable to achieve targets on
oral ULT, is to give PEGLOTICASE (A)
32. Consider referring when…
• Unclear etiology of hyperuricemia
• Refractory gout
• Difficulty in achieving target BUA
• Multiple or serious AE from ULT
Why did the ACR come up with recommendations – as other societies had published their guidelines much earlier (e.q. EULAR, British Society of Rheumatology, etc)? The goal was not to create new classification system or a paradigm shift in the way we manage gout. But rather to appraise current evidence on what is effective and safe to give to gout patients and to summarize these to reflect the best standards of care. The recommendations did not cover the diagnosis of patients with gout but instead focuses on how we should be managing gout. It assumes that a correct diagnosis of gout was made. That a thorough evaluation of co-morbid conditions was carried – particularly those which impact on how gout care would change. And a review of medications to evaluate for potential drug-drug interaction.
Rather than evaluate the strength of the recommendation, the ACR merely provides us with an assessment of the quality of evidence available to support a recommendation. It does not follow that a recommendation having a higher level of evidence would be better than something having lower quality. Nor would a lower level of evidence mean that an intervention should not be considered.
Severity is assessed by using the Pain VAS. <4 mild, 5-6 moderate, >7 severe.Duration is defined by the time from the onset of signs and symptoms of gout. <12 hours – early, 12-36 hours – established, >36 hours – lateFrequency is based on the number of flares occuring in a year. <1 – infrequent, 2-6 frequent, >7 very frequent
Large joints – ankles, knees, hips, elbows, wrists and shouldersRegions - forefoot, midfoot, hindfoot, knee, hip, wrist, elbow, shoulder
Simple tophi – lack of drainage, lack of aggressive mass or destructive effects, low risk of tophus infection, stable in size/ slow growth, lack of severe chronic tophaceous joint inflammationComplicated tophi – drainage, aggressive mass or destructive effects, high risk of infection, very rapid growth and with severe chronic tophaceous inflammation.
Recommended doses: Naproxen 500 mg BID, Indomethacin 50 mg TID, Sulindac 200 mg BIDBased on an RCT (which Dr JLY was part of) the dosing of Celecoxib was 800 mg initially then another 400 mg on D1 then 400 mg BID from D2 – D8
All life style changes – weight loss and exercise, healthy overall diet, smoking cessation, hydration- have Evidence Level C.
Consider increased OFI and urine alkalinization when using uricosurics
Start at low dose to reduce gout flares associated with ULT initiation and as risk reduction for AHS
Did not recommend Allopurinol Maintenance Dosing based on Renal Function (C)
Uricosurics - (probenecid, losartan, fenofibrate) – sulfinpyrazone (Available in the Phils) and benzbromarone were not recommended simply due to paucity of literature on their utility in such setting