Dynamic patterns and predictors of hydroxychloroquine nonadherence among Medicaid beneficiaries with systemic lupus erythematosus

https://doi.org/10.1016/j.semarthrit.2018.01.002Get rights and content

Abstract

Background

Hydroxychloroquine (HCQ) is the standard of care medication for most SLE patients, however nonadherence is common. We investigated longitudinal patterns and predictors of nonadherence to HCQ in a U.S. SLE cohort of HCQ initiators.

Methods

We used Medicaid data from 28 states to identify adults 18–65 years with prevalent SLE. We included HCQ initiators following ≥6 months without use, and required ≥1 year of follow-up after first dispensing (index date). We used the proportion of days covered (PDC) to describe overall HCQ adherence (<80% = nonadherent) and novel group-based trajectory models (GBTM) to examine monthly patterns (<80% of days/month covered = nonadherent), during the first year of use. Multivariable multinomial logistic regression models were used to examine predictors of nonadherence.

Results

We identified 10,406 HCQ initiators with SLE. Mean age was 38 (±12) years, 94% were female, 42% black, 31% white; 85% had a mean PDC < 80%. In our 4-group GBTM, 17% were persistent adherers, 36% persistent nonadherers, and 47% formed two dynamic patterns of partial adherence. Adherence declined for most patients over the first year. Compared to persistent adherers, the odds of nonadherence were increased for blacks and Hispanics vs. whites and for younger ages vs. older; increased SLE-related comorbidities were associated with reduced odds of nonadherence for persistent nonadherers (0.95, 95% CI: 0.91–0.99).

Conclusions

Among HCQ initiators with SLE, we observed poor adherence which declined for most over the first year of use. HCQ adherence is a dynamic behavior and further studies of associated predictors, outcomes, and interventions should reflect this.

Introduction

Medication nonadherence is a serious problem among patients with systemic lupus erythematosus (SLE); less than half of patients adhere to their SLE-related medications as prescribed [1]. Clinical and epidemiologic factors unique to SLE may increase nonadherence including cognitive and psychological manifestations, high disease burden among lower socioeconomic status groups, the complexity and toxicity of the medication regimens, and SLE disease activity fluctuations. Hydroxychloroquine (HCQ) is considered the backbone of SLE therapy regardless of disease severity, and it is now standard of care for all SLE patients to take HCQ continuously beginning at the time of diagnosis [2], [3], [4]. HCQ use is disease stabilizing and associated with fewer disease flares, reduced disease activity overall and less organ damage accrual [2], [4], [5], [6], [7]. Medically indicated discontinuation is uncommon with the exception of evidence of retinal toxicity, which results in most cases from cumulative exposure and occurs in 4–7.5% of patients taking HCQ for 10 years and in <1% during the first 5–7 years [7], [8].

To date, most studies of HCQ adherence are small, cross-sectional, and based in academic cohorts. Moreover, they rely on one-time often self-reported measures of adherence failing to capture the dynamic nature of adherence behavior over time. Conflicting results regarding risk factors for nonadherence, and physicians’ inability to accurately predict who is likely to nonadhere, make it difficult to know who to target and how to intervene [9], [10]. In addition, most studies included prevalent users of HCQ and therefore conflate potentially different risk factors for nonadherence among patients initiating HCQ with those who have been taking it for years. We therefore aimed to use nationwide data on patients enrolled in Medicaid, the federal-state public health insurance for low-income individuals, to describe longitudinal patterns and predictors of HCQ adherence among SLE patients newly receiving this medication. To define distinct, dynamic HCQ adherence patterns, we used a well-described but novel method, group-based trajectory models (GBTM). GBTMs have been used in psychology and other social sciences, to model underlying longitudinal patterns where there are repeated measures available for individuals that may change over time [11], [12]. In the chronic disease literature, there are a few studies that use GBTM to describe patterns of adherence behavior and the method has been shown to better capture changes in adherence over time than standard composite measures such as the proportion of days covered (PDC) [13], [14], [15], [16]. To our knowledge, GBTMs have not been previously used to describe adherence among patients with SLE. We hypothesized that GBTMs would demonstrate distinct patterns of declining adherence over the first year of use and certain sociodemographic (e.g., young age and black race) and disease-related (e.g., absence of lupus nephritis) characteristics would predict patterns of sustained nonadherence.

Section snippets

Patient cohort

We used the Medicaid Analytic eXtract (MAX) from the 29 most populated U.S. states from 2000–2010. HCQ dispensing data were unavailable in MAX for Medicaid beneficiaries living in Ohio and therefore this state was excluded, leaving 28 states in our analysis. MAX includes all billing claims, healthcare utilization, drug-dispensing data, and demographic information for Medicaid beneficiaries. We identified patients aged 18–65 years with prevalent SLE based on ≥2 International Classification of

Results

We identified 10,406 individuals with SLE who were new users of HCQ, had complete HCQ dispensing data, and 365 days of follow-up beginning at the date of HCQ initiation. The mean ± SD age was 37.7 ± 11.8 years, 94% were female, 42% were black, 31% white, 20% Hispanic (Table 1). During the baseline period, 10% had ICD-9 codes consistent with lupus nephritis, 27% with cardiovascular disease, 29% received an antidepressant medication, and 59% received corticosteroids. During the 365-day follow-up

Discussion

In this longitudinal study of Medicaid beneficiaries with SLE, adherence among HCQ initiators was poor starting one month after the first dispensing, and for most patients, adherence declined over the first year of use. While prior studies demonstrated that nonadherence among SLE patients is common, nonadherence among SLE patients enrolled in Medicaid is even more pronounced [10], [36], [37]. Our model revealed a group of persistent nonadherers, which comprised 36% of our cohort, who had very

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    Funding: This study was funded by the Rheumatology Research Foundation Investigator Award (CH Feldman), NIH 1K23 AR071500-01 (CH Feldman), NIH NIAMS R01 057327 (KH Costenbader), K24 AR066109 (KH Costenbader), and K24 AR055989 (DH Solomon).

    1

    These authors contributed equally.

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