Introduction
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Acute gout is common inflammatory arthritis in the adult US population.
Gout results from inflammation caused by precipitation of uric acid crystals from supersaturated extracellular fluid.
The ACR guidelines recognize NSAIDs, corticosteroids, and colchicine as first-line monotherapy for the treatment of gout.
Pharmacology
Pharmacology
| Property | Naproxen | Prednisone | Triamcinolone | Colchicine |
|---|---|---|---|---|
| Dose | 750 mg orally followed by 250–500 mg every 8 hours until the attack has subsided | 40 mg/day for 3 to 5 days, with or without a taper | 20–40 mg for the knee and 5 to 10 mg for smaller joints | 1.2 mg PO × 1 followed by 0.6 mg an hour later* |
| Administration | Oral | Oral | Intra-articular | Oral |
| PK/PD | Onset: 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 Effects | Edema, GI discomfort, headache, dizziness, renal dysfunction | Hypertension, fluid retention, hyperglycemia, disturbance in mood | Headache, injection site pain, influenza-like illness, pharyngitis | GI discomfort, diarrhea, nausea, neuromyopathy, and vomiting |
| Drug Interactions and Warnings | Consider 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 vaccines | Warning if considering joint sepsis, and in patients with diabetes, CVD, GI problems or psychiatric disorders | Drug interaction with CYP3A4 or P-glycoprotein inhibitors. Warning in patients with hematologic, renal, and hepatic insufficiency |
| Comments | It is critical that therapy is initiated within 24 hours of acute gout attack onset | ACR guidelines recommend intra-articular or oral corticosteroids if only one or two joints are involved | ACR guideline recommends drug started within 36 hours of attack onset | *Renal and hepatic dose adjustments |
Alternative Agents in Acute Gout
| NSAIDs | Corticosteroids | Interleukin-1 inhibitors | Other Therapies |
|---|---|---|---|
| Ibuprofen PO 400–800 mg three to four times daily | Prednisone 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 days | ACTH 40 units IM or SC every 72 hours |
| Indomethacin PO 50 mg three times daily | Triamcinolone acetonide 60 mg IM once followed by oral prednisone or prednisolone | Canakinumab (Ilaris) single dose 150 mg SC | Local 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 week | Methylprednisolone 100 mg IM once followed by oral prednisone or prednisolone | Local or regional anesthetic blocks are a potential adjunctive therapy |
Evidence
Evidence
| Author, year | Design / sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Zhang, 2014 | Observational, n=60 | IM betamethasone 7 mg × 1 vs diclofenac 75 mg BID × 7 days | Betamethasone > diclofenac pain reduction at day 3 Betamethasone = diclofenac pain reduction at day 7 Betamethasone < diclofenac adverse effects |
| Daoussis, 2013 | Observational, n=181 | IM ACTH 100 units | 78% 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, 2010 | RCT, n=184 | colchicine 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, 2007 | RCT, n=90 | prednisolone 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, 1994 | RCT, n=31 | IM 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, 1993 | RCT, n=27 | Indomethacin 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, 1991 | RCT, n=61 | etodolac 300 mg BID × 7 days vs naproxen 500 mg BID × 7 days | Significant in both treatment groups at each time interval 93–97% of patients report improved condition treated with either agent |
Conclusions
- Acute gout is a common inflammatory arthritis, and the ACR guidelines recognize NSAIDs, corticosteroids, and colchicine as first-line monotherapy options for an acute attack.
- Agent selection is driven by comorbidities and organ function: corticosteroids are favored over NSAIDs (particularly indomethacin) or colchicine in elderly patients with multiple comorbidities, glucocorticoids (intra-articular, oral, or parenteral) are preferred in renal insufficiency, and ACTH is an option when the patient is NPO. Per the ACR guidelines, intra-articular or oral corticosteroids are reasonable when only one or two joints are involved.
- Therapy should be started early in the attack – NSAIDs within 24 hours and intra-articular triamcinolone within 36 hours of onset – and colchicine requires renal and hepatic dose adjustment along with caution for CYP3A4 or P-glycoprotein interactions.
- The cited evidence supports these comparable options: low-dose colchicine matched high-dose efficacy with a placebo-like safety profile (Terkeltaub 2010), and corticosteroids were as effective as NSAIDs for pain relief with fewer adverse effects (Man 2007, Zhang 2014).
References
1. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/ 2. Khanna D, et al. 2012 American College of Rheumatology guidelines for the management of gout. Arthritis Care Res 2012;64:1447-1461. 3. Wilson L, et al. Pharmacotherapy. 2016 Aug;36(8):906-22 4. Daoussis D, et al. Joint Bone Spine. 2013 May;80(3):291-4. 5. Terkeltaub RA, et al. Arthritis Rheum. 2010 Apr;62(4):1060-8 6. Man CY, et al. Ann Emerg Med. 2007 May;49(5):670-7. 7. Siegel LB, et al. J Rheumatol. 1994 Jul;21(7):1325-7. 8. Alloway JA, et al. J Rheumatol 1993; 20:111. 9. Maccagno A, et al. Curr Med Res Opin. 1991;12(7):423-9. Monotherapy -NSAID -Systemic Corticosteroid -Colchicine Combination Therapy -Colchine + NSAID -Colchicine+ Oral Corticosteroid -Intraarticular steroid +oral colchicine, NSAID, or corticosteroid Elderly +/- Multiple Comorbidities -Corticosteroids > NSAIDS (particlarly indomethacin) or Colchicine Renal insufficiency -Intraarticular, oral, or parenteral glucocorticoids NPO -ACTH
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NSAIDs corticosteroids colchicine ACR
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