Adalimumab Persistence for Inflammatory Bowel Disease in Veteran and Insured Cohorts

ABSTRACT

Objectives: Identify predictors of persistence with adalimumab (ADA) among veterans and privately insured patients with inflammatory bowel disease (IBD) in the United States.

Study Design: Retrospective cohort study.

Methods: Patients with IBD taking ADA as their first biologic were identified from the Veterans Health Administration (VHA) database from 2009 to 2013 and the Truven Health MarketScan database from 2009 to 2012 with a 12-month follow-up. Persistence was defined as continued use 1 year after initiation. Adherence was assessed by calculating a medication possession ratio, which was dichotomized as greater than 0.86 or less than or equal to 0.86. Multivariable logistic regression was used to evaluate predictors of persistence.

Results: There were 1030 patients in the VHA population compared with 3264 patients in the privately insured (MarketScan) cohort. In MarketScan, 1800 patients (55%) remained on ADA compared with 755 (73%) in the VHA cohort. In multivariable analysis, male sex (odds ratio [OR], 1.38; 95% CI, 1.16-1.63; P <.01), Crohn disease (OR, 1.27; 95% CI, 1.02-1.57; P = .03), greater adherence (OR, 1.83; 95% CI, 1.45-2.30; P <.01), and dose escalation (OR, 1.82; 95% CI, 1.42-2.33; P <.01) were associated with higher ADA persistence in the MarketScan cohort; narcotic use (OR, 0.71; 95% CI, 0.58-0.88; P <.01) and hospitalization or new steroid use after initiation (OR, 0.04; 95% CI, 0.03-0.05; P <.01) were associated with lower persistence. In the VHA cohort, only a hospitalization or new steroid use (OR, 0.50; 95% CI, 0.36-0.70; P <.01) was associated with lower persistence.

Conclusions: Despite being older and having more comorbidities, patients in the VHA, which is an integrated healthcare system, appear to be more likely to remain on ADA at 1 year than patients in the MarketScan database. Further studies of system differences are needed to understand the reasons behind this discrepancy.

Am J Manag Care. 2018;24(12):e374-e379Takeaway Points

Among veterans with inflammatory bowel disease in the United States taking adalimumab (ADA), 73% were still taking the medication 1 year after initiation, whereas just 55% of privately insured patients remained on the drug.

• Men, patients with Crohn disease, and patients who were more adherent to ADA were more likely to remain on the drug among the privately insured patients.
• Those less likely to remain persistent among the privately insured cohort were patients who took narcotics and, among veterans, only those who were hospitalized after initiation.
• Unmeasured factors in the Veterans Health Administration, such as improved provider communication, appear to improve persistence.

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting idiopathic disorder of the gastrointestinal tract. There are approximately 1.5 million Americans with IBD,¹ and among these, 70,000 are veterans.² For those patients with moderate to severe IBD, treatment with monoclonal antibodies targeting tumor necrosis factor alpha (TNF), such as adalimumab (ADA), has been shown to reduce corticosteroid use and improve quality of life.³ Concomitant therapy with thiopurines further increases the chance of steroid-free remission.⁴ Despite the superior efficacy of anti-TNFs and thiopurines, approximately one-third of patients who initially respond to these medications lose response over the course of time, requiring a change in therapy, dose escalation, and/or reinitiation of corticosteroids.⁵ Loss of response often occurs due to the development of antibodies to the drug, which can lead to increased clearance of the drug. Nonadherence to or intermittent use of biologics has been linked to a higher risk of antibody formation,⁶ which can therefore lead to reduced persistence.

Prior studies of persistence with biologics for IBD have identified that approximately 20% of patients have stopped the drug within 6 months.⁷ Another study of persistence with ADA for all indications in Israel found that 52% stopped the drug within the follow-up period (mean = 3 years).⁸ Predictors of higher persistence from both studies include concomitant immunomodulator use, Crohn disease, and concomitant steroid use. Among patients with Crohn disease, those with the small and large intestines affected—this disease location is typically more aggressive and more likely to lead to surgery⁹—have been identified as being more likely to be persistent.⁷ In other disease states, patients with more comorbidities were less likely to be persistent with biologics.¹⁰ Patients with rheumatoid arthritis with higher persistence were noted to have higher overall health costs, but nonpharmacy costs were lower among patients who were persistent.¹¹ Patient support programs have been found to improve adherence and persistence among patients taking biologics for a broad spectrum of diseases.¹²

The aim of our study was to describe the patterns and predictors of persistence with the most commonly used anti-TNF, ADA, in a nationwide cohort of privately insured patients and a veteran population. We evaluated the effects of predictors of disease severity—including concomitant medications such as immunomodulators and narcotics, dose escalation of ADA, and hospitalizations or corticosteroid use—other comorbidities, and adherence to ADA on persistence.

METHODS

Study Design

We conducted a retrospective cohort study of administrative claims for patients with IBD in a privately insured cohort and in the Veterans Health Administration (VHA). The University of Michigan Institutional Review Board reviewed and approved this study.

Data Sources

We studied administrative claims of patients identified to have IBD from the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2012 with follow-up into 2013. MarketScan is a large administrative claims database derived from insurance claims of enrollees who are covered by large private employers in the United States. The database includes inpatient, outpatient, and pharmacy claims for approximately 50 million people.

A comparable cohort was selected from the national VHA to conduct a retrospective cohort study of patients with IBD receiving anti-TNFs from 2009 to 2013 with follow-up into 2014. An extra year of data was included in the VHA analysis to expand the cohort size. The VHA’s Corporate Data Warehouse contains data extracted from electronic health records, including pharmacy fills, inpatient records, and outpatient records, for all veterans receiving care through VHA facilities and programs across the United States. The VHA is one of the largest integrated healthcare systems in the world, caring for approximately 9 million veterans.¹³