Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26742777
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Lesinurad in combination with allopurinol: results of a phase 2, randomised,
double-blind study in patients with gout with an inadequate response to
allopurinol
#MMPMID26742777
Perez-Ruiz F
; Sundy JS
; Miner JN
; Cravets M
; Storgard C
Ann Rheum Dis
2016[Jun]; 75
(6
): 1074-80
PMID26742777
show ga
OBJECTIVES: To assess the efficacy and tolerability of lesinurad, an oral
selective uric acid reabsorption inhibitor, in combination with allopurinol
versus allopurinol alone in patients with gout and an inadequate response to
allopurinol. METHODS: Patients (N=227) with an inadequate response to
allopurinol, defined as serum urate (sUA) ?6?mg/dL on ?2 occasions ?2?weeks apart
despite ?6?weeks of allopurinol, were randomised 2:1 to 4?weeks of double-blind
treatment with lesinurad (200, 400 or 600?mg/day) or matching placebo in
combination with their prestudy allopurinol dose (200-600?mg/day). Colchicine
prophylaxis for gout flares was required. The primary end point was percent
reduction from baseline sUA levels at 4?weeks. A pharmacokinetic substudy was
also conducted. Safety was assessed throughout. RESULTS: Patients (n=208)
received ?1 dose of blinded medication. Lesinurad 200, 400 and 600?mg in
combination with allopurinol produced significant mean percent reductions from
baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with
placebo (p<0.0001, all doses vs placebo). Similar results were observed in
patients with mild or moderate renal insufficiency (estimated creatinine
clearance 30 to <90?mL/min). The incidence of ?1 treatment-emergent adverse event
was 46%, 48% and 54% with lesinurad 200, 400 and 600?mg, respectively, and 46%
with placebo (most frequent, gout flares, arthralgia, headache and
nasopharyngitis), with no deaths or serious adverse events. CONCLUSIONS:
Lesinurad achieves clinically relevant and statistically significant reductions
in sUA in combination with allopurinol in patients who warrant additional therapy
on allopurinol alone. TRIAL REGISTRATION NUMBER: NCT01001338.
free
free
free
