EULAR Releases 2016 Gout Treatment Guidelines

Jul 29, 2016



The European League Against Rheumatism (EULAR) issued new gout treatment guidelines this week, the first since 2006.

Much has changed in the understanding of gout since the guidelines were last issued.

There has been a dramatic increase in the prevalence of gout in developed countries and there is now mounting evidence for a clear association between gout and cardiovascular events, kidney failure and mortality. This “has heightened the realization that gout should never be neglected and should be treated properly,” wrote Pascal Richette, M.D., Ph.D., and colleagues in the July 25 issue of the Annals of the Rheumatic Diseases.

The 2016 recommendations are based on a systematic literature review of 984 references of studies that focused on treating flares and long-term management of gout. The guidelines were written, in part, with the primary care physician in mind since they often treat gout patients first.  [[{"type":"media","view_mode":"media_crop","fid":"50616","attributes":{"alt":"©ThamKC/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_5794995349078","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6191","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©ThamKC/Shutterstock.com","typeof":"foaf:Image"}}]]

While colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids have traditionally been used to manage gout flares, now patients have new treatment options, such as allopurinol (Zyloprim), febuxostat (Uloric), pegloticase (Krystexxa) and interleukin-1 inhibitors (anakinra, canakinumab, rilonacept) for frequent and poorly controlled flares. Because of the high cost of IL-1 blockers and an increased likelihood of infection, the EULAR task force recommends they be prescribed only for patients who have contraindications to colchicine, NSAIDs and corticosteroids.

Citing multiple studies, the authors say that urate-lowering therapy (ULT), specifically allopurinol, should be considered at first presentation of a flare. If this fails, then febuxostat, or a combination of a xanthine oxidase inhibitor with a uricosuric, should be considered. For refractory gout, EULAR recommends pegloticase.

They recommend serum uric acid (SUA) target levels of less than 6 mg/dL (360 mmol/L) for mild to moderate gout and for patients with severe gout, less than 5 mg/dL (300 mmol/L).

While new pharmacological treatments can be effective in managing gout flares, pharmacological treatments must be applied with patient education, the authors stressed repeatedly in the article. Fostering an environment in which patients take an active role in controlling flares - through medication adherence and lifestyle changes - is essential. “The task force is convinced that patients must play a key role and be fully involved in the management of their disease,” the authors wrote.

 

How the EULAR and ACR Gout Recommendations Differ

(Continued on next page.)

How the EULAR and ACR Gout Recommendations Differ

These 2016 EULAR gout recommendations differ in some aspects from the 2012 American College of Rheumatology (ACR) guidelines:

While ACR recommends allopurinol or febuxostat as first-line therapy, EULAR recommends allopurinol first and then febuxostat when allopurinol fails to reach SUA targets. The EULAR recommendations are, in part, based on the cost and availability of these treatments throughout Europe. 

Unlike ACR, EULAR recommends adjusting the allopurinol dosage to the creatinine clearance in patients with renal failure due to the increased risk of SCARs in those patients. Febuxostat is recommended as an alternative if the SUA target is not reached.

While the ACR recommends ULTs for acute attacks when anti-inflammatory treatments have been introduced, EULAR does not recommended this strategy.

 

​Three Overarching Principles

(Continued on next page.)

​Three Overarching Principles

(1) Informed Patients are Patients who Adhere to Treatment Regimens

Every person with gout should be fully informed about the pathophysiology of the disease, the existence of effective treatments, associated comDrbidities and the principles of managing acute attacks and eliminating urate crystals.”

(2) Diet and Weight Loss Counseling

Every person with gout should receive advice regarding lifestyle changes.” 

Gout is known to be associated with the excessive intake of meat, alcohol, seafood, sugar-sweetened drinks, foods rich in fructose and purine-rich vegetables. Conversely, research shows that the consumption of cherries, coffee, skim milk and low fat yogurt can control gout flares.

(3) Screen for Life-Threatening Comorbidities

“Every person with gout should be systematically screened for associated comorbidities and cardiovascular risk factors, including renal impairment, coronary heart disease, heart failure, stroke, peripheral arterial disease, obesity, hyperlipidaemia, hypertension, diabetes and smoking, which should be addressed as an integral part of the management of gout.”

 

The 11 New Recommendations:

(Cotinued on next page.)

The 11 New Recommendations:

1.      Treat acute gout flares at the "first warning" of symptoms. Drug choice  should be based on contraindications, patient history, time of initiation after flare onset and the number and type of joint(s) involved.

2.      Recommended first-line options for acute flare:  colchicine (within 12 hours of flare onset), oral corticosteroids or articular aspiration and injection of corticosteroids. Colchicine and NSAIDs should be avoided in patients with severe renal impairment.

3.      In patients with frequent flares and contraindications to colchicine, NSAIDs and corticosteroids (oral and injectable), IL-1 blockers should be considered for treating flares.

4.      Prophylaxis against flares should be fully explained and discussed with the patient. Prophylaxis is recommended during the first six months of ULT. Recommended prophylactic treatment is colchicine.

5.      ULT should be considered and discussed with every patient with a definitive gout diagnosis from the first presentation. ULT is indicated in all patients with recurrent flare (≥2/year), tophi, urate arthropathy and/or renal stones. Initiation of ULT is recommended close to the time of first diagnosis in patients presenting at a young age (<40 years), or with a very high SUA level (>8 mg/dL; 480 mmol/L) and/or comorbidities (renal impairment, hypertension, ischaemic heart disease, heart failure).

6.      For patients on ULT, SUA level should be monitored and maintained to <6 mg/dL (360 mmol/L). A lower SUA target (<5 mg/dL; 300 mmol/L) to facilitate faster dissolution of crystals is recommended for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until total crystal dissolution and resolution of gout. SUA level <3 mg/dL is not recommended in the long term.

7.      All ULTs should be started at a low dose and then titrated upward until the SUA target is reached. SUA <6 mg/dL (360 mmol/L) should be maintained lifelong.

8.      In patients with normal kidney function, allopurinol is recommended for first-line ULT, starting at a low dose (100 mg/day) and increasing by 100 mg increments every 2–4 weeks if required, to reach the uricaemic target. If the SUA target cannot be reached by an appropriate dose of allopurinol, allopurinol should be switched to febuxostat or a uricosuric, or combined with a uricosuric. Febuxostat or a uricosuric are also indicated if allopurinol cannot be tolerated.

9.      In patients with renal impairment, the allopurinol maximum dosage should be adjusted to creatinine clearance. If the SUA target cannot be achieved at this dose, the patient should be switched to febuxostat or given benzbromarone with or without allopurinol, except in patients with eGFR <30 mL/min.

10.   In patients with crystal-proven severe debilitating chronic tophaceous gout and poor quality of life, in whom the SUA target cannot be reached with any other available drug at the maximal dosage (including combinations), pegloticase is indicated.

11.   When gout occurs in a patient receiving loop or thiazide diuretics, substitute the diuretic if possible; for hypertension, consider losartan or calcium channel blockers; for hyperlipidaemia, consider a statin or fenofibrate.

 

References:

P Richette, M Doherty, et al. "2016 updated EULAR evidence-based recommendations for the management of gout," Annals of the Rheumatic DiseasesJuly 25, 2016.  DOI:10.1136/annrheumdis-2016-209707

x