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Lesinurad plus febuxostat maintain serum urate targets in gout
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Patients with tophaceous gout who were unable to achieve serum urate targets with febuxostat alone later maintained lower serum urate levels for 2 years when prescribed combination therapy of lesinurad and febuxostat, according to recent findings.
“In gout, long-term urate-lowering therapy (ULT) promotes dissolution of tissue urate crystal deposits,” Nicola Dalbeth, MBChB, MD, FRACP, professor of medicine at The University of Auckland, and colleagues wrote. “However, no studies using combined xanthine oxidase inhibition and uricosuric ULT have focused on clinical outcomes or adverse events beyond 12 months of therapy.”
To evaluate efficacy and long-term safety among patients with tophaceous gout who received combination therapy of febuxostat (Uloric, Takeda) plus lesinurad (Zurampic, Astra Zeneca), Dalbeth and colleagues conducted an extension study of the 12-month core CRYSTAL study. In the present study, the researchers analyzed outcomes among four groups: 64 patients who continued the lesinurad 200 mg regimen; 65 patients who continued the lesinurad 400 mg regimen; 33 patients who were treated with febuxostat 80 mg plus 200-mg lesinurad; and 34 patients treated with febuxostat 80 mg and lesinurad 400 mg.
Complete resolution of at least one target tophus by the extension month served as the primary endpoint, while the mean rate of gout flares requiring intervention between the end of extension month 2 and the end of extension month 12 served as the main secondary endpoint. Dalbeth and colleagues also evaluated safety assessments, including adverse events and laboratory data for the duration of the extension study.
According to researchers, by month 12 of the extension, a complete resolution in at least one target tophus was reported in 59.6% of patients in the lesinurad 200 mg continuation group, 43.5% of those in the lesinurad 200 mg extension group, 66.7% of those in the 400-mg continuation group, and 50% of those in the 400-mg extension group.
For the sum of all areas for the target tophi, Dalbeth and colleagues observed a reduction of 76.4% was observed for the lesinurad 200-mg continuation group, along with a 58.1% reduction for the 200-mg extension group, a 77.5% reduction for the 400-mg continuation group, and 62.8% for the 400-mg extension group. Between the end of extension month 2 and extension month 12, the adjusted mean number of gout flares requiring treatment was 0.6 (SE = 0.19), 1.3 (SE = 0.48), 0.2 (SE = 0.08), and 1.9 (SE = 0.93) in the lesinurad 200-mg continuation, 200-mg extension, 400-mg continuation, and 400-mg extension groups, respectively.
Additional findings showed that target sUA of less than 5 mg/dL was reached by 77.1% of patients in the lesinurad 200-mg continuation group, 79.2% of those in the 200-mg extension group, 88.5% of those in the 400-mg continuation group, and 71.4% of those in the 400-mg extension group. Safety data showed that serious treatment-emergent adverse event rates were less than 15% for all study arms, and consistent with previous findings.
“No new safety concerns were evident with longer exposure to combination therapy. Renal-related adverse events, including [serum creatinine] elevations, were observed after the first year of treatment, and ongoing monitoring of kidney function is important for patients receiving lesinurad therapy on a long-term basis,” Dalbeth and colleagues. “These data provide further support for combining a uricosuric with a xanthine oxidase inhibitor in the treatment of patients with tophaceous gout.” – by Rob Volansky
Disclosure: Dalbeth reports receiving grant support from AstraZeneca and Amgen and consulting fees from AstraZeneca, Kowa, Horizon, and Takeda. Please see the study for all other authors’ relevant financial disclosures.
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