TREATMENT OF THE ACUTE GOUT ATTACK: “A MATTER OF CONTRAINDICATIONS AND COST!!!” (3) Colchicine Cost issue and insurance coverage Drug interactions Terkeltaub RA, et al. Arthritis Rheumatol. 2011;63(8):2226.

Management of acute gouty attacks GUIDELINEs Management of acute gouty attacks Khanna D, et al. Arthritis Care & Research. 2012;64:1431. Khanna D, et al. Arthritis Care & Research. 2012;64:1447. Richette P, et al. Ann Rheum Dis. 2017 Jan;76(1):29-42. Qaseem A, et al. Ann Intern Med. 2016; doi: 10.7326/M16-0570. ACR 2012 EULAR 2016 ACP 2016 Medication - First lines: NSAIDs or Colchicine (Low-intensity)* or Steroid (Oral prednisone 0.5 mg/kg x 5-10 d stop or 2-5 d at full-dose,tapering in 7-10 d. or IM triamcinolone 60-80 mg followed by oral prednisone or intra-articular steroid or 25-40 IU ACTH subcut for NPO pts. Switch to different monotherapy Combination: NSAIDs + Colchicine or Steroid + Colchcine Off-label use: IL-1 blockers Same as ACR 2012 Corticosteroids (first line) NSAIDs (no NSAIDs preference) Colchicine (Low-intensity, acknowledge that is now more expensive than corticosteroid and NSAIDs, multiple drug interactions) (NOT IMPROVED) *Low-intensity colchicine: 1.2 mg at first sign, then 0.6 mg an hour later. - Colchicine is contraindicated in patients on dialysis. (Not dialyzable). Dose should be reduced in patients with renal insufficiency. - Colchicine dose should be reduced when used in combination with CYP3A4/P-glycoprotein inhibitors. Strong P-glycoprotein inhibitor: Cyclosporin/Tacrolimus: 0.6 mg 1 dose, to be repeated no earlier than 3 d. Strong CYP34A inhibitor: Ketoconazole, Clarithromycin, Ritonavir: 0.6 mg 1 dose or 0.3 mg bid, to be repeated no earlier than 3 d Medium CYP34A inhibitor: Verapamil, Diltiazem: 1.2 mg 1 dose, to be repeated no earlier than 3 d. Weak CYP34A inhibitor: Azithromycin: No dose reduction required: 1.2 mg at first sign, then 0.6 mg an hour later.

LONG-TERM HYPOURICEMIC AGENTs GUIDELINEs LONG-TERM HYPOURICEMIC AGENTs Khanna D, et al. Arthritis Care & Research. 2012;64:1431. Khanna D, et al. Arthritis Care & Research. 2012;64:1447. Richette P, et al. Ann Rheum Dis. 2017 Jan;76(1):29-42. Qaseem A, et al. Ann Intern Med. 2016; doi: 10.7326/M16-0570. ACR 2012 EULAR 2016 ACP 2016 Medication - First lines (XOI): allopurinol or - First lines (XOI): allopurinol or Febuxostat Febuxostat - Second line (UUA): probenecid - Second lines (UUA): probenecid (only if CrCl>50 ml/min) or combined (only if CrCl>50 ml/min) or benzpro XOI with probenecid marone (only if CrCl>30 ml/min, unavailable in the US) or combined an XOI with a UUA No specific recommendation (Acknowledging available comparable effectiveness of both allopurinol and febuxostat) When - Frequent attacks > 2 x/yr - Presence of a tophus - Nephrolithiasis - CKD > stage II - Frequent attacks > 2 x/yr - First attack, younger than 40 with SUA > 8 mg/dL - Presence of a tophus - Nephrolithiasis Recommends against initiating long-term urate-lowering therapy after a first gout attack or in patients with infrequent attacks. -Recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis in patients with Recurrent gout attacks. -”Treat-to-avoid-symptoms” (meaning???, definition???) Allopurinol - Max. starting dose 100 mg/dL - No starting dose recommended in CKD for any patients with a lower but suggesting low dose. dose of 50 mg/dL in those with CKD > stage 4. - Max. dose adjusted to CrCl if target not achieved switch to febuxostat or - Gradually titrate the dose up by 50 benzbromarone with or without allopurinol to 100 mg every 2-5 wks to achieve (except in patients with GFR<30 ml/min) SUA goal as long as adequate patient education and monitoring drug toxicity are provided (eg. Pruritus, rash, elevated transaminase) “Treat-to-avoid-symptoms, with no monitoring of urate levels” (Acknowledging treat-to-target (T2T) commonly recommended by ACR and EULAR and requirement of comparative effectiveness studies that evaluate incre- mental benefits and harms of a T2T strategy over treat-to-avoid-symptoms strategy. Target SUA - < 6 mg/dL for all - < 6 mg/dL for all - For severe or tophaceous - For severe gout (tophi, disease < 5 mg/dL frequent attacks) < 5 mg/dL - SUA < 3 mg/dL not recommended

GUIDELINEs for PROPHYLACTIC TREATMENT DURING URIC-ACID LOWERING TREATMENT Khanna D, et al. Arthritis Care & Research. 2012;64:1431. Khanna D, et al. Arthritis Care & Research. 2012;64:1447. Richette P, et al. Ann Rheum Dis. 2017 Jan;76(1):29-42. Qaseem A, et al. Ann Intern Med. 2016; doi: 10.7326/M16-0570. ACR 2012 EULAR 2016 ACP 2016 - First line: Colchicine* - First line: Colchicine or NSAIDs - Second line: NSAIDs (naproxen 220 mg bid, unless contraindicated) Duration: Duration: - At least 6 months - 6 months or - 3 months after achieving - Acknowledge that not all target SUA if no tophi patients may require or prophylaxis and discussion - At least 6 months after with patient recommended achieving target if tophi present or the last tophus has resolved No specific recommendation (acknowledging evidences available of using low-dose colchicine or low-dose NSAIDs for more than 8weeks-6 month) - Recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis in patients with recurrent gout attacks. *- Colchicine 0.6 mg once to twice a day. Lower dose is preferred in elderly patients and patients with CKD stage IV-V (0.3 mg/d or every other day). - Colchicine is contraindicated in patients on dialysis. (Not dialyzable) - Colchicine dose should be reduced when used in combination with CYP3A4/P-glycoprotein inhibitors Strong P-glycoprotein inhibitor: Cyclosporin/Tacrolimus: 0.3 mg/d or 0.3 mg every other day. Strong CYP34A inhibitor: Ketoconazole, Clarithromycin, Ritonavir: 0.3 mg/d or 0.3 mg every other day. Medium CYP34A inhibitor: Verapamil, Diltiazem: 0.6 mg/d or 0.3 mg once to twice a day.. Weak CYP34A inhibitor: Azithromycin: No dose reduction required: 0.6 mg once to twice a day.

Dalbeth N, et al. Lancet. 2016, 388;203952.