Objective Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12‐month, multicenter, randomized, double‐blind, placebo‐controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of <6.0 mg/dl. Methods Patients receiving ≥300 mg of allopurinol (≥200 mg in those with moderate renal impairment) who had serum UA levels ≥6.5 mg/dl at screening and ≥2 gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of <6.0 mg/dl at month 6. Key secondary end points were the mean gout flare rate requiring treatment (months 7–12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data. Results The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P < 0.0001). Lesinurad was not significantly superior to allopurinol alone in terms of the secondary end points: rates of gout flares and complete resolution of tophi. Lesinurad was generally well‐tolerated; the safety profile of the 200‐mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels. Conclusion Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate‐lowering therapy.

This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant proportions of patients did not achieve target sUA.

Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, 6 JRC non-sensitive subjects and 9 JRC and/or Mountain Cedar (MC) sensitive subjects were given 4 vaccine doses (each 4mg/1ml) intramuscularly (IM) at 14-day intervals. Nine JRC and/or MC sensitive subjects were given 4 doses (2 mg/0.5 ml) IM at 14-day intervals. The safety and functional biomarkers were followed for 132 d. Following this, 17 of 24 subjects were recruited into the IB trial and received one booster dose (2 mg/0.5 ml) IM approximately 300 d after the first vaccination dose to which they were randomized in the first phase of the trial. All safety endpoints were met and all subjects tolerated CryJ2-LAMP vaccinations well. At the end of the IA trial, 10 out of 12 JRC sensitive and 6 out of 11 MC sensitive subjects experienced skin test negative conversion, possibly related to the CryJ2-LAMP vaccinations. Collectively, these data suggested that the CryJ2-LAMP DNA vaccine is safe and may be immunologically effective in treating JRC induced allergy.

ObjectiveArhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout.MethodsThis was a 12‐week, randomized, double‐blind, controlled phase IIb study. Eligible patients had had ≥3 flares of gout during the previous year, had discontinued urate‐lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5–12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure.ResultsA total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were −12.5% with 600 mg arhalofenate and −16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus −0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5‐fold the baseline value were observed in the arhalofenate‐treated groups.ConclusionArhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate‐lowering antiflare therapy.