new gout management guidelines

The American College of Rheumatology recently updated their guidelines for the management of gout (see gout guidelines AmColRheum ArthRheum2020 in dropbox, or https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.41247 )).

 

Recommendations:

-- strong recommendations:

    -- initiate urate lowering therapy (ULT) for all patients with:

        -- tophaceous gout: those with one or more subcutaneous tophi

        -- radiographic damage due to gout, by any radiologic modality

        -- frequent gout flares, at least 2 annually

    -- allopurinol is the preferred 1st line ULT, including for those with moderate to severe chronic kidney disease

    -- starting dose allopurinol should be ≤100 mg per day, and lower in those with CKD (≤50mg/d); febuxostat ≤40 mg per day

    -- there should be a treat-to-target strategy: goal serum uric acid (SUA) <6 mg/dL. [as opposed to the 2012 recommendations, they do not have different thresholds for those with tophaceous gout, previously set at <5 mg/dL , due to lack of supporting evidence: see below]

    -- medications to lower SUA should be titrated over weeks to a few months, testing for SUA levels after each adjustment to achieve the goal [ie, do not wait many months to years to titrate meds to goal]

        --[they do not comment on maximum allopurinol dose, though most recent guidelines do not include an upper limit. as recent justification see http://gmodestmedblogs.blogspot.com/2017/05/higher-allopurinol-dosages-for-gout.html ]

    -- once starting ULT, provide concomitant anti-inflammatory prophylaxis therapy for at least 3 to 6 months [eg low-dose colchicine, such as 0.6mg daily]

    -- management of gout flares: colchicine (low-dose preferable: 1.2 mg immediately, then the 0.6 mg an hour later, along with ongoing anti-inflammatory therapy until the flare resolves), NSAIDs, or glucocorticoids (oral, intra-articular, or intramuscular)

        --early intervention works best, including “medication-in-pocket” strategies

 

-- other comments/conditional recommendations:

    -- if ULT is indicated, it is conditionally recommended as being okay to start during gout flare vs waiting until its resolution (no reason to wait, shorter time to effectiveness, patients already on anti-inflammatory to prevent gout recurrence, and patients more likely to adhere to meds in the setting of a painful joint)

    -- ULT should be continued indefinitely (not much evidence: one study did find that only 13% of patients who stopped ULT and maintained a SUA concentration of <7 mg/dL had no flares)

    -- for patients of Southeast Asian descent (e.g. Chinese, Korean, Thai) and for African-American patients, test for HLA-B*5801, given the associated higher risk of potentially very severe Allopurinol Hypersensitivity Syndrome. The incidence is 7.4% for those from Southeast Asian descent, 3.8% for African-Americans, and 0.7% for white and Hispanic individuals, though they do not recommend universal testing. [the addition of African-Americans was not in the 2012 recommendations, not sure why not then but is included now]. In addition starting at lower doses of allopurinol, maximum of 100 mg a day, is also preferable (as recommended)

    -- lifestyle factors: limiting alcohol intake (may be associated with 1.6 mg/dL decreased serum uric acid level), limiting purine intake (data on effect are scant, though there is a dose-response relationship between increasing purine intake and risk of gout flares), limiting high fructose corn syrup intake (there is a clear relationship between increased fructose and SUA levels, and greater consumption of high fructose corn syrup with a higher incidence of gout, though limited data of effectiveness of decreasing fructose intake), and weight loss (a small study for example found that in obese patients, a mean weight loss of 5 kg led to SUA lowering of 1.1 mg /dL).  all are conditionally recommended, regardless of disease activity. Vitamin C is not recommended

    -- switching hydrochlorothiazide to an alternate antihypertensive is reasonable regardless of disease activity [also true for other diuretics, loop ones included. not sure why they singled out HCTZ]

    -- choosing losartan preferentially as an antihypertensive, regardless of disease activity [it is uricosuric]

    -- stopping low-dose aspirin unless clearly medically indicated

    -- not adding or switching cholesterol-lowering agents to fenofibrate [though fenofibrate does lower SUA levels; they do not comment on why not to switch. i assume it is because fenofibrate is much less effective for lipid reduction than statins, and allopurinol is more effective than fenofibrate]

 

Commentary:

--these guidelines do not have the level of background justification or extensiveness of prior guidelines: eg they do not comment that decreasing the incidence of clinical gout takes about 6 months of ULT to happen. but they do give some background/justification for each of their recommendations

--to me, this is a welcome addition after the Agency for Healthcare Research and Quality (AHRQ) released their 2016 guidelines, with no recommendation of treatment for hyperuricemia to a specific target. Older guidelines also had equipoise regarding the use of allopurinol vs febuxostat (see http://gmodestmedblogs.blogspot.com/2016/03/gout-management-ahrq-report.html )

    -- this guideline downgraded the use of febuxostat both because of its high cost as well as the potential concern of cardiovascular safety (see http://gmodestmedblogs.blogspot.com/2019/03/gout-drug-feboxustat-gets-fda-boxed.html )

-- studies have been fairly clear that gouty attacks are not decreased within the 1st 6 months of ULT, and that patients who achieve even low serum uric acid levels soon after starting medications are still at increased risk of gout attacks

-- losartan is a significant uricosuric agent, unlike the other ARBs, and was even recommended in the 2012 guidelines as a major agent to consider for SUA reduction. Other antihypertensives that seem to be associated with lowering gout include amlodipine, nifedipine and diltiazem (see http://gmodestmedblogs.blogspot.com/2018/07/serum-urate-levels-and-incident-gout.html, as well as htn and uric acid losartan ccbs bmj 2012 in the dropbox, or doi:10.1136/bmj.d8190)

-- they do comment that lower levels of SUA (ie lower than <6) seem to increase the resolution of tophi and are associated with less frequent gout flares, but they do not feel there is adequate data to support these lower thresholds [though, i would still be inclined to a lower target in someone with tophaceous gout]

-- there are some small studies (consistent with my experience) that decreasing fructose intake (esp high-fructose corn syrup) is associated with significant reductions in SUA levels (on the order of 1mg/dL. though no data on decreasing gouty flares)

--as per prior blogs on gout, i also am pretty enamored of joint injection if only 1 or 2 joints involved: a topical therapy with minimal systemic effects, remarkably rapid symptomatic resolution (a few minutes), and pretty easy to do (i have even had 100% effect of injecting the 1st MTP joint, even though i think i get into the joint itself < 1/2 the time). And, there is so much pain in the affected joint by the gout that the 27 guage needle is barely noticed....


-- Allopurinol may also decrease chronic kidney disease (see http://gmodestmedblogs.blogspot.com/2018/10/allopurinol-use-may-decrease-ckd.html , and potentially cardiovascular disease (see http://gmodestmedblogs.blogspot.com/2016/03/hyperuricemia-allopurinol-decreases.html  )

    --these findings are an incentive (to me) to have a low threshold for initiating long-term daily ULT.  this seems different from initiating daily preventative therapy for migraine, for example, where the therapy has the single effect of decreasing migraine attacks. therefore, for migraine (to me), there is a different type of a conversation with the patient: does taking a daily med (with its adverse effects) outweigh the intensity/frequency/disability of continued migraine attacks at the current rate/intensity?? with gout/hyperuricemia, there may well be important added systemic benefits beyond gout attacks (which can usually be easily managed, especially if treated early with the "medication-in-pocket" approach)


geoff

 

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