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
Gout 2012: Updates to an Old Disease
GOUT 2012:Updates to an Old Disease
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 interactionsKhanna 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 forManagement of Gout. Part 2. Arth Care & Res 2012; 64 (10): 1447-61.
Levels of EvidenceA Meta-analyses >1 Randomized Clinical TrialB Single Randomized Clinical Trial Non-Randomized Studies Standards of CareC Case Studies Expert Consensus
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)
Choosing an Anti-Inflammatory Start Pain VAS Yes <7/10 MONOTHERAPY (A) No CONSIDER Start • Patient preferenceCOMBINATION • Prior response to meds THERAPY (C) • Associated co-morbids
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)
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
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)
Combination Therapy in Acute Gout• Colchicine with NSAIDs• Colchicine with Steroids• IA Steroids with Colchicine/ NSAIDs/ Oral Steroids• Consider topical ice application (B)
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)
Continuing Acute Gout CareINADEQUATE RESPONSE REVIEW the diagnosis Yes <20% in 24H CONSIDERor <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
PROPHYLAXISTo be started in all patients in whom Urate Lowering Therapy is indicated
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)
Duration of ProphylaxisChoose 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)
URATE LOWERING THERAPYPharmacologic and Non-Pharmacologic
Diet and Lifestyle Changes AVOID LIMIT ENCOURAGEOrgan meats (B) Seafood (B) Low fat or non-fat dairyDrinks with fructose(C) Sweetened fruit juices (C) products (B)Alcohol overuse (B) Sugar (C) Vegetables (C)Alcohol during an acute Salt (C)attack (C)
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
Indications for ULT• Evidence of tophus/tophi (A)• Frequent attacks (>2/year) (A)• History of nephrolithiases (C)• Chronic Kidney Disease Stage 2-5 (C)
Target Blood Uric Acid<6 mg/dl <5 mg/dlFor most gout scenarios For more durable(if without visible tophi) improvement and patients (A) with visible tophi (B)
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)
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
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
Pharmacogenetics for AHSPatients at high risk for AHS should considerscreening for HLA-B*5801 (A) – Korean descent with CKD 3 or worse (A) – Han Chinese – Thai
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)
Consider referring when…• Unclear etiology of hyperuricemia• Refractory gout• Difficulty in achieving target BUA• Multiple or serious AE from ULT