Introduction

  • 1.

    • Acute gout is common inflammatory arthritis in the adult US population.

  • 2.

    • Gout results from inflammation caused by precipitation of uric acid crystals from supersaturated extracellular fluid.

  • 3.

    • The ACR guidelines recognize NSAIDs, corticosteroids, and colchicine as first-line monotherapy for the treatment of gout.

Pharmacology

PropertiesNaproxenPrednisoneTriamcinoloneColchicine
Dose750 mg orally followed by 250 mg every 8 hours until the attack has subsided40 mg/day for 3 to 5 days, with or without a taper20-40 mg for the knee and 5 to 10 mg for smaller joints1.2 mg PO x 1 followed by 0.6 mg an hour later*
AdministrationOralOralIntra-articularOral
PK/PDOnset: 0.5-1 hr
Duration: up to 12 hrs
Renal Excretion: 95%		Onset: 1-2 hr
Elimination ½ life 2-3 hr
Renal Excretion: >95%		Onset: 12-24 hr
Duration: up to 30 days
Renal Excretion: 75%		Onset: 0.5-2 hr
Elimination ½ life 27-31 hr
Renal Excretion: 45-65%
Adverse EffectsEdema, GI discomfort, headache, dizziness, renal dysfunctionHypertension, fluid retention, hyperglycemia, disturbance in moodHeadache, injection site pain, influenza-like illness, pharyngitisGI discomfort, diarrhea, nausea, neuromyopathy, and vomiting
Drug Interactions and warningsConsider against in patients with high bleeding risk, peptic ulcer disease, heart failure, dehydration, and renal impairment.Warning with oral contraceptives, CVD, diabetes, GI problems, psychiatric disorders, and live vaccinesWarning if considering joint sepsis, and in patients with diabetes, CVD, GI problems or psychiatric disordersDrug interaction with CYP3A4 or P-glycoprotein inhibitors.

Warning in patients with hematologic, renal, and hepatic insufficiency
CommentsIt is critical that therapy is initiated within 24 hours of acute gout attack onset ACR guidelines recommend intraarticular or oral corticosteroids if only one or two joints are involvedACR guideline recommends drug started within 36 hours of attack onset

*renal and hepatic dose adjustments

Alternative Agents in Acute Gout

NSAIDSCorticosteroidsInterleukin-1 inhibitorsOther Therapies
Ibuprofen PO 400-800 mg three to four times dailyPrednisone PO 0.5 mg/kg equivalent daily for 5-10 days followed by discontinuation

Oral methylprednisolone dose pack may be considered		Anakinra (Kineret) 100 mg SC daily for 3 daysACTH 40 units IM or SC every 72 hours
Indomethacin PO 50 mg three times dailyTriamcinolone acetonide 60 mg IM once followed by oral prednisone or prednisoloneCanakinumab (Ilaris) Single dose 150 mg SCLocal ice application is the most effective non-pharmacologic therapy
Celecoxib PO 800 mg followed by 400 mg on day one then 400 mg twice daily for 1 weekMethylprednisolone 100 mg IM once followed by oral prednisone or prednisolone Local or regional anesthetic blocks are a potential adjunctive therapy

Evidence

Author, yearDesign/sample sizeIntervention & ComparisonOutcome
Zhang, 2014Observational, n=60IM betamethasone 7 mg x 1
vs
diclofenac 75 mg BID x 7 days		Betamethasone > diclofenac pain reduction at day 3
Betamethasone = diclofenac pain reduction at day 7

Betamethasone < diclofenac adverse effects
Daoussis, 2013Observational, n=181IM ACTH 100 units78% of patients improved after one day after a dose

Minimal impact on blood pressure and serum potassium
Elevation in fasting blood sugar for 24 hours
Terkeltaub, 2010RCT, n=184colchicine 1.8 mg total over 1 hour
vs
colchicine 4.8 mg total over 6 hours
vs
Placebo		Low-dose colchicine and high dose colchicine = comparable efficacy

Low-dose colchicine safety profile = same as placebo
Man, 2007RCT, n=90prednisolone 30 mg/APAP 1g
vs
indomethacin 50 mg/APAP 1 g		Prednisolone/APAP is as effective as oral indomethacin/acetaminophen in relieving pain but ↓ adverse effects.
Siegel, 1994RCT, n=31IM adrenocorticotropic hormone 40 IU
vs
IM triamcinolone acetonide 60 mg		Resolution of all symptoms occurred at an average of 8 days for both groups.

No adverse reactions were noted in either group

11 reinjections in the ACTH group vs 5 reinjections in the triamcinolone acetonide group
Alloway, 1993RCT, n=27Indomethacin 50 mg TID
vs
IM triamcinolone acetonide 60 mg		Resolution of all symptoms occurred at 8 days for a patient taking indomethacin vs 7 days with triamcinolone
Maccagno, 1991RCT, n=61etodolac 300 mg BID x 7 days
vs
naproxen 500 mg BID x 7 days		Significant in both treatment groups at each time intervals

93-97% of patients report improved condition treated with either agent

Conclusions

References

  • Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/
  • Khanna D, et al. 2012 American College of Rheumatology guidelines for the management of gout. Arthritis Care Res 2012;64:1447–1461.
  • Wilson L, et al. Pharmacotherapy. 2016 Aug;36(8):906-22.
  • Daoussis D, et al. Joint Bone Spine. 2013 May;80(3):291-4.
  • Terkeltaub RA, et al. Arthritis Rheum. 2010 Apr;62(4):1060-8.
  • Man CY, et al. Ann Emerg Med. 2007 May;49(5):670-7.
  • Siegel LB, et al. J Rheumatol. 1994 Jul;21(7):1325-7.
  • Alloway JA, et al. J Rheumatol 1993; 20:111.
  • Maccagno A, et al. Curr Med Res Opin. 1991;12(7):423-9.
MonotherapyCombination TherapyElderly ± Multiple ComorbiditiesRenal insufficiencyNPO
• NSAID
• Systemic Corticosteroid
• Colchicine		• Colchicine + NSAID
• Colchicine + Oral Corticosteroid
• Intraarticular steroid + oral colchicine, NSAID, or corticosteroid		• Corticosteroids > NSAIDs (particularly indomethacin) or Colchicine• Intraarticular, oral, or parenteral glucocorticoids• ACTH
Tags: NSAIDs corticosteroids colchicine ACR