There were 4,166 new users of urate-lowering drugs, 97% of whom were initiated on allopurinol. Over 70 percent (n=2,929) had a gap in therapy, meaning they had at least one period lasting greater than 60 days during which no days were covered by a prescription for any urate-lowering drug. Those with a gap in therapy were more likely to be younger (mean age 62 versus 64, p <.0001) at the time of urate-lowering drug initiation, have fewer comorbid conditions based on the Charlson score (p<.0001), no hospitalizations (p=.0014), and fewer encounters for gout in the year prior to urate-lowering drug initiation (mean encounters 1.59 versus 1.86, p<.0001).
The characteristics of those with a gap in therapy are given in . The majority of patients were male (76%), and had a mean age of 63 (±15) at the time of the gap. On average, they had 1.97 (±2.76) visits with a provider for gout in the 12 months prior to the gap in therapy and used 3.46 (±3.47) different medications. In 75% of patients, the gap occurred in the first year of therapy. Over the study period 54% had one gap, 25% had two gaps and 22% had three or more gaps. Use of medications typically prescribed for gout flares in the 12 months prior to the gap in urate-lowering drug use, including nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids, occurred in 57%, 37% and 27% of the patients, respectively. The median duration of urate-lowering drug use in the 12 months prior to the gap was 120 days (IQR 170).
Characteristics of the study population with at least a 60 day gap in therapy after urate-lowering drug initiation.
In , we present the Kaplan-Meier estimates of the cumulative probability of return to urate-lowering drug therapy. An estimated 50% of patients returned to treatment within 8 months of the gap and by 4 years 75% had resumed urate-lowering drug use. presents the results of the Cox proportional hazards model examining the association between patient characteristics and the rate at which medication use was resumed in the first year after the gap. After controlling for health plan, variables associated with return to treatment included age, duration of urate-lowering drug therapy prior to the gap and receipt of NSAIDS and glucocorticoids. Specifically, being aged 45 to 54, 55 to 64 and 65 to 75 was associated with resuming urate-lowering drug use as compared to those <45 years of age (Hazard Ratio [HR] 1.37, 95% CI, 1.14-1.65; HR 1.26, 95% CI, 1.05-1.53; and HR 1.38, 95% CI, 1.15-1.66 respectively). Greater duration of urate-lowering drug use prior to the interruption increased the probability of return to treatment (HR 1.45, 95% CI, 1.26-1.68; HR 2.15, 95% CI, 1.86-2.48; HR 1.92, 95% CI, 1.69-2.19 for the second, third and fourth quartile of use respectively as compared to the lowest quartile of use). Receipt of NSAIDs (HR 0.84, 95% CI, 0.75-0.93) and glucocorticoids (HR 0.83, 95% CI, 0.74-0.93) in the year prior to the gap was associated with a reduced likelihood of resuming therapy. Factors including number of comorbidities, number of encounters associated with a gout diagnosis or any diagnosis, number of medications, and hospitalization were not associated with a return to treatment in the first year.
The Kaplan-Meir estimate of the cumulative probability of returning to treatment with urate-lowering drugs in gout patients who have had a gap in therapy.
Cox proportional hazards analysis of baseline variables associated with a return to urate-lowering drug use within the first year after an interruption in therapy after controlling for health plan.
When the model was rerun assessing factors associated with return to therapy after 1 year (), the occurrence of a hospitalization (HR 0.65, 95% CI, 0.48-0.89) in the year prior to the gap was associated with a reduced likelihood. The number of gout encounters prior to the gap was inconsistently related to a return to therapy. Variables including number of comorbidities, number of medications, duration of urate-lowering drug use prior to the gap, and receipt of NSAIDs and glucocorticoids were not significantly associated. Finally, we tested the robustness of our observed associations between covariates and return to treatment by defining a gap in urate-lowering drug use of at least 90 days instead of 60 days. The strengths of the associations were essentially the same for return to therapy within 1 year except that use of glucocorticoids was no longer significant. For the model assessing return to therapy after 1 year, age was no longer significant.
Cox proportional hazards analysis of baseline variables associated with a return to urate-lowering drug use 1 year after an interruption in drug use after controlling for health plan.