Combination therapy with lesinurad and allopurinol increases the percentage of gout patients who achieve target serum uric acid levels, a benefit that persists for least 2 years, according to the findings of an extension study presented at the annual meeting of the American College of Rheumatology in Washington, DC.
The 12-month extension study, led by Kenneth G. Saag, MD, MSc, of the University of Alabama at Birmingham, enrolled 716 gout patients who participated in the 12-month phase III core studies (CLEAR 1 and CLEAR 2). Patients in the lesinurad 200 mg plus allopurinol arm or lesinurad 400 mg plus allopurinol arm of the core studies and were enrolled in the extension trial continued on their therapies. Patients who received allopurinol alone in the core studies were randomized to receive either lesinurad 200 mg or 400 mg in addition to allopurinol.
In the core studies, about 65% of patients in the lesinurad 200 mg group and about 80% in the lesinurad 400 mg group had a serum uric acid level below 6 mg/dL—the efficacy endpoint— at the end of the studies. These proportions remained constant over the 12 months of the extension study.
In the core studies, about 30% of patients who received allopurinol alone had a serum uric acid level below 6 mg/dL at the end of these studies. The proportion increased to about 70% after 1 month of receiving lesinurad 200 or 400 mg in addition to their allopurinol treatment, and remained relatively constant for the duration of the extension study.
The extension study revealed no new safety concerns.
Lesinurad was approved by the FDA on December 22, 2015 for use in patients fail to achieve target serum uric acid levels while on xanthine oxidase inhibitors alone. Xanthine oxidase inhibitors work by lowering uric acid production. Lesinurad works by inhibiting uric acid reabsorption by the kidneys, thereby increasing renal excretion of uric acid.
“Gout is predominately a disease of under excretion of serum urate, and most of our focus has been on xanthine oxidase inhibition, which targets an important pathway but not the primary pathway for most individuals,” Dr Saag told Renal & Urology News. He called the availability of a new uricosuric agent an important advance in the treatment of gout.
“About half the people who take the standard dose of allopurinol, 300 mg per day, don’t achieve the serum urate target of 6 [mg/dL] or below,” Dr Saag said. “It really emphasizes the importance of having new therapies for managing gout.”
Whenever possible, he said, clinicians should make an effort to dose escalate xanthine oxidase inhibitors, either allopurinol or febuxostat, “since we know that these drugs at higher doses, in people who can tolerate them, are efficacious.” For patients who cannot tolerate higher doses or whose uric acid levels remain high despite dose escalation, “this is where the addition of a uricosuric drug like lesinurad would fit in.”
1. Saag KG et al. Examination of serum uric acid (sUA) lowering and safety with extended lesinurad + allopurinol treatment in subjects with gout. Poster presented at the 80th annual meeting of the American College of Rheumatology in Washington, DC, Nov.11-16.