Guidance on the initiation and use of urate-lowering therapies was among the strong recommendations in the updated gout guideline recently issued by the American College of Rheumatology, said Brian F. Mandell, MD, PhD, in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Dr. Brian F. Mandell

The 2020 American College of Rheumatology Guideline for the Management of Gout is “intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient,” said Dr. Mandell, chair of academic medicine at the Cleveland Clinic in Ohio and cochair of the conference. However, “there was a hope that, with additional evidence since the previous guideline issued in 2012, the recommendations are more firmly based and will improve care,” he said.

Of 42 recommendations, 16 were strong, and these included guidance on several points: when to initiate urate-lowering therapy and using a treat-to-target strategy for lowering serum uric acid to less than 6 mg/dL; prophylaxis against attacks; the use of allopurinol as the first-choice drug and how to avoid hypersensitivity reactions; the use of pegloticase (Krystexxa); and treating flares.

Hyperuricemia does not automatically equal gout, Dr. Mandell said. A 2018 published analysis of data from several large cohorts including 18,889 adults who were gout-free at baseline showed that serum uric acid levels could not accurately predict an initial gout attack. Therefore, the guideline conditionally recommends against initiating any pharmacologic urate-lowering therapy in patients with asymptomatic hyperuricemia. The guideline authors intentionally did not include the presence of comorbidities or deposits of uric acid in making their recommendation. But when advising an individual patient, these factors plus the patient’s age and family history should be considered, he said. “Individualize the decision to use ULT [urate-lowering therapy] to prevent possible future flares,” he advised, with consideration of age, the effects of the flare on the patient’s life, and challenges in treating flares.

For patients who are being treated with urate-lowering therapy, a published study indicated that if treatment is discontinued, “gout attacks will recur, depending on the new serum urate level,” Dr. Mandell said. “Maintenance of low SUA [serum uric acid] must be lifelong to stop attacks,” he emphasized, noting that this is counter to a management guideline published by the American College of Physicians in 2017.

“For patients starting any ULT, we strongly recommend allopurinol over all other urate-lowering therapies as the preferred first-line agent for all patients, including those with CKD [chronic kidney disease] stage 3 or higher,” according to the new guideline, which also recommends starting at a low dose followed by dose titration to target versus starting at a higher dose.

Two reasons in support of a slow up-titration of urate-lowering therapy are a lower frequency of mobilization flares and a possibly lower chance of allopurinol hypersensitivity reactions, Dr. Mandell said.

Although the guideline recommends allopurinol over probenecid, “probenecid works well as monotherapy and effectively as add-on therapy to a xanthine oxidase inhibitor, and it is cheap,” Dr. Mandell said.

Allopurinol can be associated with life-threatening hypersensitivity reactions, but most of these have been associated with a higher-than-recommended starting dose, according to the literature, he noted. The new guideline suggests checking for the HLA-B*5801 haplotype in high-risk demographic groups, and if it is present, to use an alternative to allopurinol if possible

The updated guideline also carries a strong recommendation for the use of pegloticase for patients with frequent gout flares and nonresolving subcutaneous tophi, but it strongly recommends against switching to pegloticase for patients with infrequent gout flares and no tophi.

However, Dr. Mandell said that he will consider off-label treatment of gout with pegloticase “in patients where a shorter time to response really matters,” which is consistent with his belief that, within these treatment principles, the management of gout must be individualized to the specific patient.

For treating acute gout flares, the guideline recommendations strongly supports the use of oral colchicine, NSAIDs, or glucocorticoids as an appropriate first-line therapy, based on patient factors and preferences, instead of using interleukin-1 inhibitors or adrenocorticotropic hormone. However, the interleukin-1 inhibitor anakinra has shown relatively rapid and successful response in treating patients hospitalized with acute gout, Dr. Mandell said. No large, randomized, trials have been conducted, but he cited his experience at the Cleveland Clinic in Ohio, where anakinra is the most common treatment for acute gout on inpatient consults, and he cited a representative small study of 26 patients in which 73% showed “significant response” within 5 days of treatment, which meant that they were able to move and bear weight without pain. In addition, a more recent study of 100 hospitalized patients in the Journal of Rheumatology, found that 75% showed a rapid response to anakinra and improvement or resolution of flares within 4 days, Dr. Mandell said.

Dr. Mandell disclosed relationships with companies including Horizon, Ardea/AstraZeneca/Ironwood, and Takeda. He served as coauthor on the 2012 American College of Rheumatology gout guideline.

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