Gout medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

• The medical therapy of Gout differs for acute flares, chronic condition and maintenance therapy for prevention of acute flares.

• The main stay of therapy is pain managament, ideally acheived with NSAIDS and oral or intra articular Glucocorticoids.

• Colchicine is usually used for maintainance therapy, however; within 24 hours of symptom onset, low dose colchicine can be used.

• For treatment resistant Gout, lesinurad with Xanthine oxidase inhibitors as a combination is used.

• Other, less standard methods of treatment include the use of topical creams, ice packing and increasing mobility for reducing pain.

Medical Therapy

Medical Therapy

The goal of medical therapy in gout is to: 

·      Provide effective treatment in acute gout attack

·      Prevent acute flares through prophylaxis

·      lower uric acid levels to prevent flares of gouty arthritis and to prevent deposition of urate crystals in body tissue 

In 2012, the American College of Rheumatology (ACR) published guidelines for management of gout. It includes systemic nonpharmacological and pharmacological therapeutic approaches to hyperuricemia as well as therapy and anti-inflammatory prophylaxis on acute gouty arthritis. A brief descript of the recommendations is as follows:  

Treatment for acute gouty arthritis 

·      Acute gout attack should be treated with pharmacologic therapy (evidence C), and that treatment should be preferentially initiated within first 24 hours of onset (evidence C).

·      Access the intensity of the attack based on severity of pain and the number of joints involved.

·      For a mild/moderate gout severity (6 of 10 on a 0 –10 pain visual analog scale) involving 1 or a few small joints or 1 or 2 large joints, initiating monotherapy with options being oral nonsteroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, or oral colchicine (evidence A for all drug categories).

o  NSAIDs: Approved medications are naproxen, indomethacin (both evidence A), and sulindac (evidence B). They should be initiated at their full dosing at either the Food and Drug Administration (FDA)– or European Medical Agency–approved anti-inflammatory/ analgesic doses. It should not be tapered with symptomatic improvement; instead full dose should be administered till complete resolution.

o  Colchicine: Acute gout can be treated with a loading dose of 1.2 mg, followed by 0.6 mg 1 hour later (evidence B). This can then be followed by a gout attack prophylaxis dosing beginning 12 hours or later and continued till the attack resolves (evidence C). If the patient was already on prophylactic colchicine and received acute gout regimen in the last 2 weeks, then consider other therapeutic options i.e. corticosteroid, NSAID.

o  Corticosteroids: Corticosteroids can be given as an initial monotherapy. Prednisone, or prednisolone at a starting dosage of at least 0.5 mg/kg per day for 5–10 days and then discontinued (evidence A). Alternatively, a full dose for 2–5 days can be given, followed by tapering for 7–10 days, and then discontinued (evidence C). While oral corticosteroid is the preferred route, intra-articular route can be considered for acute gout of 1 or 2 large joints (evidence B).

·      For a severe acute gout attack (7 of 10 on a 0 –10 pain visual analog scale) and in patients with an acute polyarthritis or involvement of more than 1 large joint, combination therapy should be considered. Recommendation is to initiate simultaneous use of full doses (or, where appropriate, a full dose of 1 agent and prophylaxis dosing of the other) of 2 of the pharmacologic modalities as recommended above.

·      If the patient was previously on an established pharmacologic uric acid lowering therapy (ULT), it is recommended to be continued without interruption during an acute attack (evidence C), i.e. do not stop ULT therapy during an acute flare.  

Prophylaxis to prevent acute gout flares 16339094, 21846852, 20370912, 21353107, 15570646

It is recommended that for all cases of gout, where urate lowering therapy is started, a prophylaxis for acute flares should be started as well, given that gout attacks are common in early ULT (evidence A). 16339094, 21846852, 20370912, 21353107 

The first-line for this purpose is oral colchicine (evidence A) 21353107, 15570646, or low-dose NSAIDs (evidence C). 

A low-dose of colchicine as 0.5 mg or 0.6 mg taken orally once or twice a day is the recommendation, with dosing further adjusted downward for moderate to severe renal function impairment and potential drug–drug interactions) 21480191. 

The duration of treatment should be greater of at least 6 months (evidence A) 16339094 20370912, 21353107, 3 months after achieving target serum urate levels in patient with no tophi on physical exam (evidence B), or 6 months after achieving desired urate levels appropriate for the patient with one of more tophi (evidence C). 

Management of chronic gout/chronic tophaceous gouty arthropathy:

 

Once the diagnosis of gout is established, a systematic pharmacologic as well as non-pharmacologic management approach should be initiated. A set of baseline recommendations for all patients are: 

·      Patient education on the disease, its treatment options and their objectives, including the particular role of uric acid excess in gout and as the key long-term treatment target (evidence B) 22679303.

·      Consider diet and lifestyle modification

·      Always consider elimination of serum urate– elevating prescription medications e.g. thiazide and loop diuretics, niacin, and calcineurin inhibitors (evidence C)

·      Always consider secondary causes of hyperuricemia for all gout patients

·      A clinical evaluation of gout disease activity and its burden should be done for each patient by history and a thorough physical examination for symptoms of arthritis and signs such as tophi and acute and chronic synovitis (evidence C).  

Nonpharmacological urate lowering therapy

 

Certain diet and lifestyle measures are advised for the majority of patients with gout (evidence B and C for individual measures). Many of them are recommended for decreasing the risk and frequency of acute gout attacks (20035225) and also to lower serum urate levels.

This emphasis on diet and lifestyle choices is to promote and maintain ideal health as well as for the prevention and optimal management of comorbidities in gout patients, which include cardiovascular diseases 16871533, 18504339, diabetes mellitus, hyperlipidemia, and hypertension. 

Gout patients should limit their consumption of purine-rich meat and seafood (evidence B) (22648933) as well as high fructose corn syrup–sweetened soft drinks and energy drinks (evidence C), and encouraged the consumption of low-fat or nonfat dairy products (evidence B) (21285714).

Alcohol intake is advised to be reduced for all gout patients, especially of beer (evidence B). In CTGA and in patients with inadequate control of disease, abstinence is recommended during periods of active arthritis (evidence C). 

Pharmacological urate lowering therapy (ULT) and serum urate target

Pharmacological therapy to lower serum uric acid levels is indicated in any patient with established diagnosis of gout with

·      Prior gout attacks (2 or more per year) and current hyperuricemia (evidence A )

·      Tophus or tophi by clinical exam or imaging study (evidence A)

·      CKD stage 2–5 or end-stage renal disease, which by itself, is an appropriate indication for pharmacologic ULT (evidence C)

·      Past urolithiasis (evidence C) 

The goal is to attain a serum urate level at a minimum of less than 6 mg/dl (evidence A). Serum urate level should be lowered sufficiently so to have a dependable improve in signs and symptoms of the disease, including palpable and visible tophi detected by physical examination, and that this may involve therapeutic serum urate level lowering to below 5 mg/dl (evidence B). 

The recommended first line is xanthine oxidase inhibitor therapy with either allopurinol or febuxostat (evidence A). There is no preference of either XOI over the other XOI drug. ULT can be started during an acute gout attack, provided an effective anti-inflammatory therapy has already been initiated (evidence C)

·      Allopurinol should be started with a dose no greater than 100 mg/day (50 mg/day in stage 4 or worse CKD) (evidence B), then gradually titrate maintenance dose upward every 2–5 weeks to appropriate maximum dose in order to achieve desired serum uric acid level (evidence C) Prior to initiation, in selected patient subpopulations at higher risk for severe allopurinol hypersensitivity reaction (e.g., Koreans with stage 3 or worse CKD, and Han Chinese and Thai irrespective of renal function), consider HLA–B*5801 (evidence A)

·      Probenecid is the first choice among uricosuric agents (evidence B). It is recommended to monitor urinary uric acid levels during its therapy (evidence C). With a creatinine clearance of 50 ml/minute, it is not recommended as first-line ULT monotherapy (evidence C). History of urolithiasis and elevated uric acid level in urine also contraindicates its use (evidence C). Monitor urinary pH and consider urine alkalinization (e.g., with potassium citrate), in addition to increased fluid intake, as a risk management strategy for urolithiasis (evidence C).  

Probenecid was recommended as an alternative first-line option in case of contraindication or intolerance to at least 1 xanthine oxidase inhibitor (evidence B). However, probenecid should not be used as a first-line monotherapy when creatinine clearance is below 50 ml/minute. 

It is recommended that regular monitoring of serum urate levels be done every 2–5 weeks during drug titration; including continued measurements every 6 months once the desired level is achieved (evidence C).

Clinical practice guidelines address treatment. However, trials comparing glucocorticoids (steroids) and non-steroidal anti-inflammatory agents (NSAIDs) were not published till after the guidelines.

A nurse-led protocol with treatment goal of 6 mg/dL was beneficial.

Regarding medications, if there are no mitigating factors in choosing a drug, glucocorticoids, non-steroidal anti-inflammatory agents (NSAIDs), and colchicine all work; however, colchicine consistently causes drug toxicity.

A combination treatment is ice four times a day with oral prednisone 30 mg orally tapered over 6 days (30 mg for two days, 20 mg for two days, 10 mg for two days) and colchicine 0.6 mg/day. An advantage of this regimen is the reduced toxicity from the low dose of colchicine and that the colchicine helps prevent flares if allopurinol is later started. Colchicine has been combined with NSAIDs that are not metabolized by the CYP3A4 isoenzyme of cytochrome P-450 (naproxen is not metabolized by CYP3A4). Combining glucocorticoids with NSAIDs increased the risk for gastrointestinal drug toxicity