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Gout!

Mizuho Morrison, DO and Matthew DeLaney, MD
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NSAIDs, corticosteroids, and colchicine can all be used to treat acute gout. While these agents have similar efficacy, they have vastly different side effect profiles.

 

Pearls:

  • NSAIDS, steroids, and colchicine have all been shown to be effective treatment options for gout.

  • Barring contraindications to use, colchicine may reduce pain due to gout, but should be started as soon as possible after onset of a flare and dosing should be 1.2 mg followed by 0.6 mg 1 hour later.

  • A 2020 study comparing naproxen with colchicine found 1) no difference in pain reduction scores between the two groups and  2) increased adverse effects with colchicine.

 

According to the American College of Physicians, there are 3 main treatment options for the management of gout:   NSAIDS, steroids, and colchicine.(1) How much do they help?  

  • NSAIDS

    • When compared with placebo, NSAIDS have been shown to be better in reducing pain due to gout. 

    • The type of NSAID doesn’t appear to matter.

    • Must be cautious when prescribing to patients over 65, with renal impairment, or with a history of GI bleed.

  • Steroids

    • PO:  no placebo controlled trials, mostly indirect/anecdotal evidence that they work.

    • Intraarticular:  commonly used, almost no evidence to support or refute.

  • Steroids vs. NSAIDS

    • An RCT of 90 patients compared prednisolone/acetaminophen vs. indomethacin/acetaminophen. (2)

      • They found similar rates of analgesia, but higher adverse events for indomethacin (~64% vs. ~26%).

        • Most adverse events were nausea and indigestion. About 11% had a GI bleed.

  • Colchicine

    • Multiple anti-inflammatory mechanisms of action.

    • Problematic side effect profile:

      • Narrow therapeutic window with a number needed to harm of only 2. 

      • Reported fatalities with single doses as low as 7 mg.

    • Dosing and side effects:  

      • Early study: 1 mg followed by 0.5 mg every 2 hours until symptom relief or adverse effects occurred. (3)

        • 100% of patients got diarrhea, 90% before getting good pain relief.

      • 2010 study of high vs. low dosing showed reduced rates of diarrhea with a lower dose. (4)

        • High dose (HD): 1.2 mg followed by 0.6 mg every hour for 6 h\

        • Low dose (LD): 1.2 mg followed by 0.6 mg 1 h later

        • Results:

          • At 24 hours ~35% of patients in both groups had ⩾ 50% improvement in their joint pain (15% of the placebo group had similar pain relief).
          • The number needed to treat was 4 in the HD group and 5 in LD. 
          • Side effects were significantly greater in the HD group.
            • HD: 77% had diarrhea,19% had severe diarrhea, and 17% had vomiting. 
            • LD: 23% had diarrhea, none had severe diarrhea, and none had vomiting.
      • Experts provide an option for additional therapy with 0.5–0.6 mg once or twice daily until gout symptoms resolve. 

    • Timing of administration:  

      • Consensus is to start as soon as possible after onset of attack.

      • American College of Rheumatology recommends starting no longer than 36 h after the onset of the gouty flare 

      • European guidelines say to start within12 h.

    • Contraindications:

      • Renal or hepatic impairment

      • Don’t use with these meds:

        • CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, grapefruit juice, erythromycin, verapamil, etc.)

        • Inhibitors of P-glycoprotein (e.g. clarithromycin, ketoconazole, cyclosporine, etc.)

    • Bottom line:  colchicine has been shown to be effective in reducing pain due to gout, but should be started as soon as possible after onset of a flare and dosing should be 1.2 mg followed by 0.6 mg 1 hour later.

  • Naproxen vs. colchicine

    • A 2020 RCT compared naproxen (750 mg x 1, then 250 mg tid x 7days) with colchicine (500 mcg tid x 4 days). (6)

      • Results:

      • Similar pain scores between the two groups.

      • Side effects:
        • Worse in the colchicine group. 
        • Diarrhea (46% vs 20%) and headache (20% vs 10%)

 

References:

  1. Qaseem A, et al; Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Jan 3;166(1):58-68. PMID: 27802508.

  2. Man CY, et al. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med. 2007 May;49(5):670-7.PMID:17276548

  3. Ahern MJ, et al. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med. 1987 Jun;17(3):301-4. PMID: 3314832.

  4. Terkeltaub RA, et al. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010Apr;62(4):1060-8. PMID: 20131255.

  5. Turner J, Cooper D. Does Colchicine Improve Pain in an Acute Gout Flare? Ann Emerg Med. 2015 Sep;66(3):260-1. doi: 10.1016/j.annemergmed.2015.04.006.

  6. Epub 2015 Apr 24. Review. PubMed PMID: 25920385.

  7. Roddy E, et al. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care. Ann Rheum Dis. 2020 Feb;79(2):276-284. PMID: 31666237.

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Urgent Care RAP May 2020 Written Summary 907 KB - PDF

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