Urate-lowering Therapy for Prevention of Gout: Prespecified Analyses from the CKD-FIX Trial

Anushree Tiku¹, Neil Boudville², Fiona Brown³, Alan Cass⁴, Phiilip Clarke⁵, Richard Day⁶, Janak de Zoysa⁷, Bettina Douglas⁸, Randall Faull⁹, David Harris¹⁰, Carmel Hawley¹¹, Graham Jones⁶, John Kanellis³, Elaine Pascoe¹¹, Suetonia Palmer¹², Vlado Perkovic¹³, Gopala Rangan¹⁰, Donna Reidlinger¹¹, Laura Robison¹¹, Robert Walker¹⁴, Giles Walters¹⁵, David Johnson¹¹, Sunil Badve¹³ and Nicola Dalbeth⁷, ¹The George Institute of Australia, Sydney, Australia, ²University of Western Australia, Perth, Australia, ³Monash University, Melbourne, Australia, ⁴Menzies School of Health Research, Darwin, Australia, ⁵University of Oxford, Oxford, United Kingdom, ⁶University of New South Wales, Sydney, Australia, ⁷University of Auckland, Auckland, New Zealand, ⁸Princess Alexandra Hospital, Brisbane, Australia, ⁹University of Adelaide, Adelaide, Australia, ¹⁰University of Sydney, Sydney, Australia, ¹¹University of Queensland, Brisbane, Australia, ¹²University of Otago, Christchurch, New Zealand, ¹³The George Institute for Global Health, Sydney, Australia, ¹⁴University of Otago, Dunedin, New Zealand, ¹⁵The Canberra Hospital, Canberra, Australia

Meeting: ACR Convergence 2021

Keywords: CKD, clinical trial, gout, Randomized Trial

Session Information

Date: Sunday, November 7, 2021

Title: Metabolic & Crystal Arthropathies – Basic & Clinical Science Poster I (0660–0682)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: The CKD-FIX randomized controlled trial showed that allopurinol did not slow decline of estimated glomerular filtration rate (eGFR) over 104 weeks in patients with chronic kidney disease (CKD) at risk of progression. The aim of this pre-specified analysis was to assess if allopurinol prevents incident gout in the CKD-FIX trial population.

Methods: In the CKD-FIX trial, 369 adults with CKD stage 3 or 4, no history of gout, and risk of kidney disease progression (urinary albumin-to-creatinine ratio ≥265 mg/g or eGFR decrease ≥3.0 mL/min/1.73 m
² in the preceding year) were randomized to receive placebo (n=184) or allopurinol up to 300mg daily (n=185). Gout flares were self-reported using a questionnaire at each study visit over 104 weeks. Additionally, the association of incident gout and baseline serum urate (normouricemia and hyperuricemia [based on a serum urate cut point of >6.8mg/dL], or as tertiles]) was analyzed.

Results: Three patients withdrew immediately after randomization. The remaining 363 patients (mean eGFR 31.7 mL/min/1.73 m², mean serum urate 8.2 mg/dL) were included in the analysis. At the end of the 12-week dose-escalation phase, 126 (69.2%) of 182 patients in the allopurinol arm were receiving 300mg daily. A total of 22 (6.1%) participants experienced 31 discrete flare episodes over 104 weeks (placebo group 20 flares in 13 patients; allopurinol group 11 flares in 9 patients). There was no significant difference between placebo and allopurinol groups in gout incidence. However, there were differences in timing of gout flares, with more flares in the allopurinol group in the first 24 weeks, and conversely more flares in the placebo group after 24 weeks (Figure, P=0.02). Across both groups, the most common affected joint region was the ankle. Of those participants who developed incident gout during follow-up, 19 (86%) had hyperuricemia at baseline. There was no association between incident gout and baseline serum urate stratified by hyperuricemia and normouricemia (P=0.14), however, there was an association between incident gout and baseline serum urate tertile, with the highest incidence of gout in those with serum urate in the highest tertile, that is, above 8.7mg/dL (P=0.004).

Conclusion: In people with CKD at risk of progression, incident gout is uncommon, and is associated with serum urate above 8.7mg/dL. Compared with placebo, allopurinol does not change the incidence of gout over a two year period, with more flares in the first 24 weeks of treatment, and fewer flares after 24 weeks.

Number of gout flares before and after 24 weeks; placebo group shown in left panel, allopurinol group shown in right panel.

Disclosures: A. Tiku, None; N. Boudville, None; F. Brown, None; A. Cass, None; P. Clarke, None; R. Day, None; J. de Zoysa, None; B. Douglas, None; R. Faull, None; D. Harris, None; C. Hawley, None; G. Jones, None; J. Kanellis, None; E. Pascoe, None; S. Palmer, None; V. Perkovic, None; G. Rangan, None; D. Reidlinger, None; L. Robison, None; R. Walker, None; G. Walters, None; D. Johnson, Baxter Healthcare, 2, 5, 6, 12, Travel Sponsorship, Fresenius Medical Care, 2, 5, 6, 12, Travel Sponsorship, AstraZeneca, 2, AWAK, 2, Bayer, 2, ONO, 6, 12, Travel Sponsorship, BI & Lilly, 6, Amgen, 12, Travel Sponsorship; S. Badve, None; N. Dalbeth, AstraZeneca, 2, JW Pharmaceutical Corporation, 2, PK Med, 2, Horizon, 2, Selecta, 2, Dyve Biosciences, 2, Arthrosi, 2, Amgen, 5.

To cite this abstract in AMA style:

Tiku A, Boudville N, Brown F, Cass A, Clarke P, Day R, de Zoysa J, Douglas B, Faull R, Harris D, Hawley C, Jones G, Kanellis J, Pascoe E, Palmer S, Perkovic V, Rangan G, Reidlinger D, Robison L, Walker R, Walters G, Johnson D, Badve S, Dalbeth N. Urate-lowering Therapy for Prevention of Gout: Prespecified Analyses from the CKD-FIX Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/urate-lowering-therapy-for-prevention-of-gout-prespecified-analyses-from-the-ckd-fix-trial/. Accessed .

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