Article Text
PDF
Abstract
Background Gout is caused by crystal deposition due to persistent hyperuricemia. EULAR1 and other guidelines recommend a target sUA of <5–6 mg/dL (0.30 to 0.36 mmol/L) depending on severity. Despite physiological plausibility and abundant literature evidence there is an absence of consensus among physicians on the targets and necessity of long term urate lowering therapy (ULT)2.
Objectives To investigate the effects of sUA and target sUA <5–6 mg/dl with respect to the occurrence of GF, flares requiring treatment (GFRT) and the percent change in the area of tophi (TR) from baseline irrespective of treatment arms.
Methods Data of 1213 patients (PT) was pooled from CLEAR trials3&4, two randomised, double-blind, placebo-controlled Phase 3 studies that evaluated Lesinurad 200/400 mg daily in combination with allopurinol vs allopurinol. Prophylaxis for flares was given from baseline to month (M) 5. PT who met the sUA target of <5–6 mg/dl at M 6 and 12 were compared against those not on target with respect to the TR from baseline using a Wilcoxon test. In addition, the mean sUA measurements for PT with or without GFs and GFRT was compared at M 6 and 12 using a t-test.
Results PT with sUA on target <5–6 mg/dl showed a larger decrease (increase in percent reduction) in area of tophi with a difference of 27.9%, and 17.3% at M 12 only compared to the PT not on target (table 1). The mean sUA levels were 0.227 mg/dL lower for PT with GF and 0.389 mg/dL lower for PT with GFRT compared to PT without GF and GFRT at M 6 (table 2), but not at M 12.
Percent Change from baseline Area of tophi vs. SUA on target <5–6 mg/dL at M 6 and 12
Mean sUA at M 6 and 12 by occurrence of GF and GFRT
Conclusions These results confirm that sUA on target <5–6 mg/dl is essential for TR, and longer the control better the TR. The lower mean sUA levels for PT with GF and GFRT was observed at M6 and not at M 12, maybe owing to the fact that flares are common during the first months of ULT initiation and then taper off and urate deposits were more fragile and not completely dissolved. Also M 6 and 12 may not be optimal to observe statistically significant differences between treatments with respect to TR, GF and GFRT.
References [1] Richette P, et al. Ann Rheum Dis 2017;76:29−42.
[2] Qaseem A, et al. Ann Intern Med2017;166(1):58–68.
[3] Saag KG, et al. Arthritis Rheumatol2017;69:203–12.
[4] Bardin T, et al. Ann Rheum Dis2017;76:811–20.
Disclosure of Interest F. Perez-Ruiz Consultant for: Grünenthal, Menarini, Speakers bureau: Grünenthal, Menarini, P. Richette Consultant for: Grünenthal, Speakers bureau: Grünenthal, R. Karra Employee of: Grünenthal, I. Wild Employee of: Grünenthal, H. Hagedorn Employee of: Grünenthal, P. Kandaswamy Employee of: Grünenthal, T. Bardin Consultant for: Grünenthal