The terms 'acute' and 'chronic' gout have contributed to a false dichotomy in regards to decisions about timing and indications for urate-lowering therapy (ULT), leading to a misconception that only patients with 'chronic' gout require ULT. A consensus statement by the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) to clarify labels for gout disease elements has highlighted that terms such as 'acute' and 'chronic' gout should not be used, and instead, the terms 'gout flare', 'intercritical gout' and 'chronic gouty arthritis' are recommended. Accordingly, the 2020 ACR gout guideline does not use the terms 'acute gout' and 'chronic gout' in its discussion of gout management.
Management of Hyperuricemia: Urate-lowering Therapy
The cornerstone of gout treatment is the reduction of urate using ULT, which includes xanthine oxidase inhibitors (XOI) (allopurinol and febuxostat), uricosuric agents (probenecid, benzbromarone, lesinurad, dotinurad) and recombinant porcine-like uricase that metabolizes urate to allantoin, pegloticase. Not all therapies are available in all markets.
Indications for Urate-lowering Therapy
The 2020 American College of Rheumatology (ACR) gout guideline strongly recommends initiating ULT in patients with one or more clinically evident tophi, radiographic damage reflecting gouty bony erosion or two or more gout flares annually. ULT was also conditionally recommended for patients with more than one gout flare annually, and for patients with comorbid stage at least 3 chronic kidney disease (CKD), serum urate level more than 9 mg/dl or kidney stones. Allopurinol is strongly recommended as the preferred first line agent for all patients, including those with moderate to severe CKD, unless there are contraindications such as hypersensitivity to prior allopurinol exposure or consideration of potential high risk due to HLA-B*5801. Dosing considerations for various ULTs available in the USA are outlined in Table 1.
Starting ULT during a gout flare is conditionally recommended by the 2020 ACR gout guideline, reflecting the need for shared decision making. This is similar to the 2012 ACR gout guideline, with additional studies considered in the updated 2020 guideline in which some trial data did not suggest a large risk for the theoretical concern about prolonging a flare.[13–15] Ensuring appropriate patient education and follow-up may be challenging when a patient is in the midst of an intensely painful flare. On the contrary, patients may be more motivated to make significant changes immediately while seeking care for a flare.
Titrating ULT to achieve a target serum urate level of less than 6 mg/dl is strongly recommended over fixed dosing in the ACR gout guideline, supported by data from a number of randomized controlled trials (RCTs) regarding clinical benefits. In the pegloticase RCT, there was a significant reduction in flares and tophi at 6 months. In a febuxostat RCT in early gout, there was a significant reduction in gout flares noted only after 6 months. In a UK RCT, patients randomized to a target-to target strategy (T2T) nurse-led intervention were significantly more likely to achieve a serum urate of less than 6 mg/dl and have lower flare frequency and greater tophus resolution at 2 years. Other studies have also been supportive of a T2T approach, including pharmacy led T2T programmes that were more effective than usual care in patients achieving target urate levels.[19,20] In patients who do not achieve target urate level despite XOI, uricosurics and other interventions and who continue to have frequent flares or nonresolving tophi, pegloticase is recommended. For patients on therapy, it is conditionally recommended to continue ULT indefinitely.
Prophylaxis When Starting Urate-lowering Therapy
When initiating ULT, the 2020 ACR gout guideline strongly recommends administering prophylactic antiinflammatories such as NSAIDS, colchicine or prednisone to prevent gout flares. A stepwise dose escalation of febuxostat from 10 to 40 mg/day has been demonstrated to be comparable with addition of colchicine prophylaxis to fixed-dose febuxostat 40 mg daily for the prevention of gout flares during ULT titration.
Gout Flare Management
The ACR guideline strongly recommends NSAIDs, colchicine or glucocorticoids (oral or intra-articular) as first-line therapy for the management of gout flares, without differentiating between particular agents, over anti-IL-1 therapy. Of note, in patients who are already on colchicine prophylaxis, colchicine could be used for flare treatment as long as liver and kidney function permit, and there are no major contraindications or drug-drug interactions. IL-1 inhibitors, anakinra and canakinumab, though currently not FDA-approved for such use, are reserved for those unresponsive to therapy or who are unable to tolerate NSAIDS, colchicine and steroids.
Data on direct comparative effectiveness of interventions for gout flare management are minimal. A 2021 network meta-analysis reported that canakinumab has a potential advantage compared with other anti-inflammatory interventions for pain reduction and joint tenderness at day 2. Intravenous (i.v.) and intramuscular (i.m.) steroids may also be superior to ibuprofen, COX-2 inhibitors, colchicine and oral corticosteroids in pain reduction at day 2. Acetic acid derivative NSAIDs are probably superior to ibuprofen NSAIDS for joint swelling reduction at day 2.
Dietary and Lifestyle Modifications
Recent studies have highlighted the importance of genetic factors and obesity as being prominent determinants of hyperuricemia. A 2018 meta-analysis reported that the variance in urate levels due to genetics was higher than dietary factors. However, although variances in hyperuricemia explained by obesity, nonadherence to the DASH diet, alcohol use and diuretic use were overall low, the population attributable risk of obesity was estimated to be 44%; in contrast, for the DASH diet and alcohol use, the population attributable risks were 9 and 8%, respectively.
Although ULT is the mainstay of gout management, dietary and lifestyle modifications may be useful adjuncts to ULT. Dietary interventions alone often do not lead to significant urate reduction in patients with gout and caution should be undertaken when discussing dietary factors to avoid patient blaming. Nonetheless, weight loss may improve urate levels and risk of flares, and is recommended by the ACR gout guideline, which also conditionally recommends limiting consumption of alcohol, purines and high fructose corn syrup. No recommendations could be made regarding cherry/cherry extract, omega-3 fatty acids and dairy due to a paucity of data.
Curr Opin Rheumatol. 2022;34(2):118-124. © 2022 Lippincott Williams & Wilkins