Gradual dose escalation of allopurinol appears to be effective and well-tolerated in gout patients for whom creatinine clearance-based doses of allopurinol fail to achieve target urate levels, according to findings.
In the level 1 study, researchers evaluated patients with gout in New Zealand. Patients received at least one creatinine clearance (CrCL)-based allopurinol dose for at least 1 month and had a serum urate level of at least 6 mg/dL. Patients were randomly assigned on a 1:1 ratio to remain on the current dose of allopurinol (control, n=93) or to allopurinol dose escalation (DE, n=90). The DE group received increased monthly doses of allopurinol until serum urate (SU) was 6 mg/dL on three consecutive visits or until adverse events occurred. Primary efficacy outcome was absolute decrease in SU at the last study visit (last visit or 12 months for patients who died or were lost to follow-up).
Researchers found that at the final visit, the mean change in SU was -0.34 mg/dL in the control group vs. -1.5 mg/dL in the DE group, with a mean difference of 1.2 mg/dL mg daily vs. 290 mg daily in those not at target. Of the control group, 14% achieved SU of greater than 6 mg/dL at each of the last 3 monthly visits, while 59% of the DE group attained this goal. From baseline to the final visit, the mean percentage change in SU from baseline to last visit was -3.3% in the control group vs. -17.8% in the DE group. At least one self-reported gout flare was reported in 59% of the control group and in 54% of the DE group. By the conclusion of the study, a decrease in the use of prophylaxis was seen in both groups.
During the study, 43 serious adverse events (SAEs) occurred in 25 control participants and 35 SAEs were seen in DE participants. Five deaths occurred in each group; none of the deaths were related to allopurinol.
The researchers considered one of the SAEs, increase in international normalized ratio (INR) to be likely related to allopurinol. This SAE occurred in a participant in the DE group who initiated warfarin after elective mitral valve replacement.
ases in liver function tests were frequent in both groups; the researchers also noted a few moderate increases in gamma glutamyl transferase.
Renal function changes did not differ between the two randomized groups.
The researchers wrote, “Data from [National Health and Nutrition Examination Survey] NHANES 2007–2008 showed that of the individuals with gout 74% had hypertension, 71% had stage 2 [chronic kidney disease] CKD, 53% were obese, 26% had diabetes, 14% had a history of myocardial infarction and 10% had a history of stroke. Thus, our population is representative of people with gout.” -by Jennifer Byrne
Please see the full study for a list of relevant disclosures.