Abstract
Objectives To determine dosing patterns and examine predictors of filled hydroxychloroquine (HCQ) prescriptions in patients with systemic lupus erythematosus (SLE) with end-stage renal disease (ESRD).
Methods This was a retrospective cohort study of patients with SLE in the US Renal Data System (USRDS) database in fiscal year 2011. All patients were Medicare Part D beneficiaries. Patients with a diagnosis of SLE were identified by the International Classification of Diseases, 9th revision code 710. The prevalence, dosing, and predictors of filled HCQ prescriptions (demographic factors, dialysis type, and provider subspecialty) were determined.
Results There were 10,276 patients with SLE identified; 2048 (19.9%) had a prescription for HCQ filled. The mean daily dose of HCQ was 321 mg (range 58–2000 mg). The most common daily doses were 200 (n=768, 37.5%) and 400 mg (n=1161, 56.7%). In multivariable logistic regression analysis, significant predictors of filled HCQ prescriptions included black/African-American race (OR 1.34, 95% CI (1.17 to 1.46)), hemodialysis (1.50, 95% CI (1.29 to 1.74)), and care from a rheumatologist (5.06, 95% CI (4.56 to 5.62)). Negative predictors of filled HCQ prescriptions included male gender (OR 0.72, 95% CI (0.63 to 0.83)) and those aged 45 years or older (compared to 20 years old and younger, aged 45–64 years, OR 0.66, 95% CI (0.54 to 0.79); aged 65–74 years, OR 0.58, 95% CI (0.44 to 0.76); aged 75 years and older, OR 0.56, 95% CI (0.39 to 0.82)).
Conclusions In patients with SLE with ESRD, the dosing strategies for HCQ with regard to potential toxicity and disparities in prescribing patterns need further study.
Introduction
End-stage renal disease (ESRD) is a common and serious complication of systemic lupus erythematosus (SLE). The risk of progressing to ESRD in patients with SLE over 10 years is 20%.1 Previously, it was thought that SLE disease activity subsides once ESRD is established2; however, after initiating dialysis, disease activity may persist in up to half of patients with SLE,3 and under-treatment of SLE flares in patients with ESRD has been associated with an increased risk of mortality.4
Hydroxychloroquine (HCQ) is considered to be a cornerstone in the management of patients with SLE.5 HCQ is renally excreted6 and, in patients with renal impairment, it has been advised that lower doses of HCQ be used,7 as several studies suggest that renal insufficiency increases the risk of retinal toxicity from HCQ.8–10 However, how often, and in what doses, HCQ is prescribed to patients with SLE and ESRD has not been well described. The purpose of this report was to use data from the US Renal Data System (USRDS) to determine the frequency, dose, and predictors of filled HCQ prescriptions in patients with SLE and ESRD.
Materials and methods
Sample
The USRDS is a national database of patients with ESRD in the USA, including 2.497 million persons. All patients with ESRD, regardless of insurance coverage, are included in the USRDS. For this study, we utilized the hospital, patient, physician/supplier claims, and Medicare Part D data sets of the USRDS. To limit heterogeneity in the sample, USRDS patients who had a kidney transplant and were not on dialysis were excluded.
All 10,276 patients with SLE and current enrollment in the Medicare Part D prescription drug plan present in the USRDS during fiscal year 2011 were included in the analysis. Fiscal year 2011 was the latest year available to have all data complete. The International Classification of Diseases, 9th revision, Clinical Modification (ICD-9) code 710 was used to identify patients with a diagnosis of SLE in the USRDS core claims and physicians’ claims data sets. The core claims and physicians’ claims data sets were merged with the Medicare Part D beneficiary data file with filled HCQ prescriptions (including dosage) to determine those patients with SLE who were Medicare Part D beneficiaries and had filled an HCQ prescription. The daily dose of HCQ was calculated as the product of the strength (200 mg) and the quantity dispensed divided by the days’ supply. The overall frequency of patients with SLE in the USRDS who filled an HCQ prescription among the cohort as well as the mean, mode, and range of daily doses was determined.
Measures
Predictors of being a patient with SLE in the USRDS with Medicare Part D benefits and a filled HCQ prescription that have also been examined in the general population of patients with SLE included demographic variables (age, race, gender) and subspecialty care;11 additionally, type of dialysis (hemodialysis vs other) was included. Age was categorized into the following five categories, with age 20 years and younger as the reference group: aged 20 years and younger, 21–44 years, 45–64 years, 65–74 years, and 75 years and older. Gender was categorized as female (reference) and male. The race variable consisted of whites (reference, including Hispanic and non-Hispanic whites), blacks/African-Americans, Asians, and Native Americans.
Statistical analysis
Descriptive analyses (table 1) stratified by the presence or absence of a filled HCQ prescription are presented with frequencies and percentages for these categorical covariates. A χ2 test was used to assess significance. Logistic regression was used to determine the relationship of age, race, gender, type of dialysis, and subspecialty care (rheumatologist vs not) to a filled HCQ prescription. Bivariate and multivariable models are presented (table 2).
Characteristics of patients with systemic lupus erythematosus with end-stage renal disease stratified by presence of a filled hydroxychloroquine prescription (N=10276)
Univariate and multivariable predictors of filled hydroxychloroquine prescriptions (n=10276)
Results
Baseline characteristics of the study cohort are shown in table 1. Among the 10,276 patients with SLE, 2048 (19.9%) filled prescriptions for HCQ. The mean daily dose of HCQ prescribed was 321 mg with a median of 400 mg and a range of 58–2000 mg. Only one patient in the cohort filled a prescription for the highest dose of 2000 mg. Similarly, only one patient filled a prescription at the next highest dose of 1200 mg. The third highest dose identified was 800 mg, with 11 patients filling a prescription at that dose. The two most frequently found daily doses were 200 mg daily (n=768 (37.5%)) and 400 mg daily (n=1161 (56.7%)). There were significant differences in gender, race, age groups, type of dialysis, and subspecialty provider, based on the presence of a filled prescription for HCQ (table 1). Approximately 31% of patients in this sample were cared for by a rheumatologist; among these patients, 61% had filled a prescription for HCQ (table 1).
In univariate analysis, males were less likely to fill an HCQ prescription than females (OR 0.63, 95% CI (0.55 to 0.72), table 2). Compared to whites, blacks/African-Americans (OR 1.56, 95% CI (1.41 to 1.72)) and Native Americans (OR 1.44, 95% CI (1.13 to 1.84)) were more likely to have filled HCQ prescriptions (table 2). Compared to those 20 years of age or less, those aged 45–64 (OR 0.67, 95% CI (0.57 to 0.81)), 65–74 (OR 0.55, 95% CI (0.47 to 0.67)), and those aged 75 years or older (OR 0.47, 95% CI (0.32 to 0.67)) were less likely to have a filled prescription for HCQ (table 2). Those on hemodialysis (vs other renal replacement therapies) were more likely to fill a prescription for HCQ (OR 1.50, 95% (1.29 to 1.74)). Finally, for patients receiving care from a rheumatologist, the odds of filling an HCQ prescription were five times larger than for those seeing a non-rheumatologist (OR 5.31, 95% CI (4.79 to 5.88)).
In multivariable analyses, males remained less likely to fill HCQ prescriptions (OR 0.72, 95% CI (0.63 to 0.83)); only blacks/African-Americans were more likely to take HCQ prescriptions than whites (OR 1.31, 95% CI (1.17 to 1.46)). Compared to those 20 years of age or less, participants aged 45–64 (OR 0.66, 95% CI (0.54 to 0.79)), 64–75 (OR 0.58, 95% CI (0.44 to 0.76)), and those aged 75 years or more (OR 0.56, 95% CI (0.39 to 0.82)) were all less likely to fill HCQ prescriptions (table 2). HCQ prescriptions were more likely among those on hemodialysis (OR 1.50, 95% CI (1.29 to 1.74)) and those receiving care from a rheumatologist remained substantially more likely to have a filled prescription for HCQ (OR 5.06, 95% CI (4.56 to 5.62)).
Discussion
In the USRDS, 20% of patients with SLE who were also Medicare Part D beneficiaries filled a prescription for HCQ, and dose adjustment for renal failure was uncommon. Women, African-Americans, and those receiving hemodialysis are more likely to fill prescriptions for HCQ. Male patients and those patients older than 45 years of age were less likely to fill prescriptions for HCQ. Among the predictors examined, care by a rheumatologist was the strongest positive predictor of filling a prescription for HCQ.
Only 20% of patients in this cohort filled a prescription for HCQ. This is less than what has been reported in community-based cohorts of patients with SLE, in which the prevalence of HCQ use has been estimated at 55/100 person-years,11 50%,12 and 48–68%.13–15 Our data are in accord with a small study where it was suggested that patients with SLE and renal disease are less likely to receive prescriptions for HCQ than patients with SLE with normal kidney function.12
Despite the concern for retinal toxicity when using HCQ in renal disease,8 ,9 our data indicate that a number of patients with SLE do receive prescriptions for HCQ. Among the patients in our cohort who did fill an HCQ prescription, there was often no dose adjustment made, although a wide range of doses was observed. The minimum daily dose (58 mg) and maximum daily dose (2000 mg) observed in this study may represent alternative treatment strategies, such as twice weekly dosing, or a short-term loading dose, respectively. The optimal dose of HCQ in ESRD cannot be determined from these data, as the data set does not include information on disease activity or HCQ-related complications. Importantly, dialysis has not been shown to significantly lower HCQ levels.16
In this cohort of patients with SLE and ESRD, similar to what has been reported in patients with SLE without ESRD, female gender12 and younger age11 are predictors of HCQ use. The reasons why black/African-American patients with SLE and ESRD and those on hemodialysis are more likely to fill a prescription for HCQ are not clear but may reflect greater disease severity in these populations.17 ,18 That care by a rheumatologist was a predictor of a filled HCQ prescription in ESRD is in accord with data from community-based practices stating that care by a rheumatologist is a substantial predictor of HCQ use.11
There are several limitations to this study. First, the duration of SLE was not captured. Second, the reasons for an HCQ prescription were not known; in particular, there was no information on SLE disease activity (the ICD-9 codes for SLE and SLE nephritis are the same) or toxicities relative to HCQ. Third, patients who were prescribed the medication but did not fill the prescription were not captured. Finally, the study is cross-sectional in nature, and does not capture the length of time that HCQ was filled for, or, in fact, whether it was ever taken by the patient.
In conclusion, a prescription for HCQ is filled by 20% of patients with SLE and ESRD. Dose adjustment of HCQ for renal failure is not provided in the majority of these cases. Future studies should address the efficacy and toxicity of HCQ dosing strategies in patients with SLE with ESRD.
Footnotes
Funding This work was supported by a reserve fund research grant from Dialysis Clinic, Inc (NSN) and the Translational Research Program of the Department of Medicine, Augusta University.
Disclaimer This work does not reflect the views of the Veterans Health Administration or of the US government. The data reported here have been supplied by the US Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.
Competing interests None declared.
Ethics approval Augusta University IRB.
Provenance and peer review Not commissioned; externally peer reviewed.
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