Gout guidelines call for treat-to-target strategy using allopurinol
ATLANTA — The 2019 ACR gout guidelines call for treating patients to a target serum urate level of 6 mg/dL, a marked departure from the 2012 document, according to speakers at ACR/ARP 2019.
Tuhina Neogi, MD, PhD, professor of epidemiology at the Boston University School of Public Health and chief of rheumatology at the Boston Medical Center, suggested that gout is “poorly managed” among the nearly 9 million Americans with the disease. “Without adequate urate-lowering therapy (ULT), patients continue to have painful flares,” Neogi, who is the primary author of the recommendations, said in her presentation. “One of my patients said they would rather get shot, again, than experience another gout flare.”
John FitzGerald, MD, interim chief of rheumatology and clinical professor of medicine at the University of California, Los Angeles, presented the methodology of the guideline development. “After the literature review, we included 130 studies,” he said, and added that the group raised and answered 57 Population/Intervention/Comparison/Outcome (PICO) questions, 30 of which dealt with ULT management.
Cost of therapy was included, and outcomes ranged from gout flare to tophi, quality of life, activity limitation, and patient global assessment, according to FitzGerald. The experts used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and ultimately arrived at “strong” or “conditional” recommendations.
Perhaps the most surprising recommendation is for a treat-to-target strategy for ULT, which lies in contrast to recommendations offered by the American College of Physicians (ACP). “Patients should be started at a low dose of allopurinol and titrated up to reach a target of 6 mg/dL,” Neogi said. “This recommendation has been very controversial, because another professional organization says that a treat-to-target strategy is wrong. We believe that since the last guidelines, enough studies have been published to support the idea that lowering serum urate to below 6 mg/dL has shown meaningful improvements in flares and reducing tophi.”
Moreover, the data support a dose of allopurinol considerably higher than 300 mg per day, Neogi added. “The concerns that higher doses are detrimental are unsupported by any data,” she said.
Other highlights include a strong recommendation for the use of allopurinol as first line ULT, even among patients with chronic kidney disease. Anti-inflammatory prophylaxis using colchicine, NSAIDs, or prednisone for 3 to 6 months, as opposed to less than 3 months, is also strongly recommended when starting ULT. Ongoing evaluation and prophylaxis as needed is strongly recommended in these patients if they continue to have flares.
A conditional recommendation calls for ULT initiation even among patients who have infrequent gout flares, kidney stones, serum urate of 9 mg/dL or greater, or chronic kidney disease — defined as CKD 3. “In these cases, shared decision-making with the patient is recommended,” Neogi said.
In another novel conditional recommendation, HLA-B*5801 testing before allopurinol initiation is suggested for patients of Southeast Asian or African American descent, who have a higher prevalence of HLA-B*5801. However, a conditional recommendation against testing for HLA-B*5801 is suggested for patients of other ethnic or racial backgrounds.
Several other members of the guideline panel presented, including Ted R. Mikuls, MD, MSPH, Umbach Professor of Rheumatology and vice chair of research at the University of Nebraska Medical Center. “Another question we asked was how long patients should remain on ULT,” he said. “There is a conditional recommendation for continuing ULT indefinitely over stopping ULT.”
Mikuls added that there are conditional recommendations regarding lifestyle management. “We conditionally recommend limiting alcohol, purine, and high fructose corn syrup,” he said.
Nicola Dalbeth, MD, an academic rheumatologist at the University of Auckland, in New Zealand, covered gout flares. “We strongly recommend low-dose colchicine over high-dose colchicine for gout flares,” she said. “For ongoing flares, we conditionally recommend using ice as adjuvant pain relief over no adjuvant treatment.”
Dalbeth added that when managing a patient experiencing a first or second flare, it is conditionally recommended to wait until the flare is over before initiating ULT.
N. Lawrence Edwards, MD, professor of medicine in the Division of Clinical Immunology at the University of Florida in Gainesville, suggested that for patients with asymptomatic hyperuricemia, the guidelines conditionally recommend against initiating any ULT.
That said, Edwards underscored the importance ULT in many clinical scenarios. “If the patient has radiographic damage, ULT is recommended,” he said. “If the patient has frequent flares, ULT is recommended.”
In closing the session, Neogi covered situations when it may be necessary to switch from allopurinol. “We conditionally recommend switching to febuxostat (Uloric, Takeda) rather than adding uricosuric,” she said.
As for switching to pegloticase (Krystexxa, Horizon) in patients who fail to respond to, or are unable to tolerate, allopurinol, she suggested that this decision should be based on clinical activity. “If the patient has infrequent flares or ongoing tophi, switch to pegloticase,” she said. “If there are no flares and no tophi, do not switch to pegloticase.” – by Rob Volansky
Neogi T. Gout management: New ACR clinical guideline. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Edwards, Neogi, and Mikuls report no relevant financial disclosures. Dalbeth reports associations with Abbvie, Amgen, AstraZeneca, Dyve BioSciences, Hengrui, Horizon, Janssen, Kowa, and Pfizer.