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The American Journal of Managed Care December 2018
Feasibility of Expanded Emergency Department Screening for Behavioral Health Problems
Mamata Kene, MD, MPH; Christopher Miller Rosales, MS; Sabrina Wood, MS; Adina S. Rauchwerger, MPH; David R. Vinson, MD; and Stacy A. Sterling, DrPH, MSW
From the Editorial Board: Jonas de Souza, MD, MBA
Jonas de Souza, MD, MBA
Risk Adjusting Medicare Advantage Star Ratings for Socioeconomic Status
Margaret E. O’Kane, MHA, President, National Committee for Quality Assurance
Reducing Disparities Requires Multiple Strategies
Melony E. Sorbero, PhD, MS, MPH; Susan M. Paddock, PhD; and Cheryl L. Damberg, PhD
Cost Variation and Savings Opportunities in the Oncology Care Model
James Baumgardner, PhD; Ahva Shahabi, PhD; Christopher Zacker, RPh, PhD; and Darius Lakdawalla, PhD
Patient Attribution: Why the Method Matters
Rozalina G. McCoy, MD, MS; Kari S. Bunkers, MD; Priya Ramar, MPH; Sarah K. Meier, PhD; Lorelle L. Benetti, BA; Robert E. Nesse, MD; and James M. Naessens, ScD, MPH
Patient Experience During a Large Primary Care Practice Transformation Initiative
Kaylyn E. Swankoski, MA; Deborah N. Peikes, PhD, MPA; Nikkilyn Morrison, MPPA; John J. Holland, BS; Nancy Duda, PhD; Nancy A. Clusen, MS; Timothy J. Day, MSPH; and Randall S. Brown, PhD
Relationships Between Provider-Led Health Plans and Quality, Utilization, and Satisfaction
Natasha Parekh, MD, MS; Inmaculada Hernandez, PharmD, PhD; Thomas R. Radomski, MD, MS; and William H. Shrank, MD, MSHS
Primary Care Burnout and Populist Discontent
James O. Breen, MD
Currently Reading
Adalimumab Persistence for Inflammatory Bowel Disease in Veteran and Insured Cohorts
Shail M. Govani, MD, MSc; Rachel Lipson, MSc; Mohamed Noureldin, MBBS, MSc; Wyndy Wiitala, PhD; Peter D.R. Higgins, MD, PhD, MSc; Sameer D. Saini, MD, MSc; Jacqueline A. Pugh, MD; Dawn I. Velligan, PhD; Ryan W. Stidham, MD, MSc; and Akbar K. Waljee, MD, MSc
Medicare Advantage Control of Postacute Costs: Perspectives From Stakeholders
Emily A. Gadbois, PhD; Denise A. Tyler, PhD; Renee R. Shield, PhD; John P. McHugh, PhD; Ulrika Winblad, PhD; Amal Trivedi, MD; and Vincent Mor, PhD
Provider-Owned Insurers in the Individual Market
David H. Howard, PhD; Brad Herring, PhD; John Graves, PhD; and Erin Trish, PhD
Mixed Messages to Consumers From Medicare: Hospital Compare Grades Versus Value-Based Payment Penalty
Jennifer Meddings, MD, MSc; Shawna N. Smith, PhD; Timothy P. Hofer, MD, MSc; Mary A.M. Rogers, PhD, MS; Laura Petersen, MHSA; and Laurence F. McMahon Jr, MD, MPH

Adalimumab Persistence for Inflammatory Bowel Disease in Veteran and Insured Cohorts

Shail M. Govani, MD, MSc; Rachel Lipson, MSc; Mohamed Noureldin, MBBS, MSc; Wyndy Wiitala, PhD; Peter D.R. Higgins, MD, PhD, MSc; Sameer D. Saini, MD, MSc; Jacqueline A. Pugh, MD; Dawn I. Velligan, PhD; Ryan W. Stidham, MD, MSc; and Akbar K. Waljee, MD, MSc
Veterans with inflammatory bowel disease taking adalimumab appear to be more likely to remain on the drug 1 year after initiation than patients who are privately insured.
Sample Selection

Individuals were identified as having IBD in the MarketScan cohort based on the presence of a single inpatient encounter or 2 outpatient claims on different days with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of Crohn disease (555.X) or ulcerative colitis (UC) (556.X) between 2009 and 2012. Patients were excluded if they did not have at least 12 months of continuous coverage with pharmacy benefits and 12 months of follow-up after initiation of ADA. Patients’ data were therefore included until the conclusion of 2013. When patients had multiple periods of coverage, only the most recent coverage period was examined to ensure that relevant outcomes were captured. There is no validated method to classify patients into a particular IBD phenotype (Crohn disease or UC) in this large administrative cohort. We therefore elected to use a method previously studied in other large insurance data sets,14 where the diagnosis of Crohn disease or UC was assigned based on the majority of the 9 most recent ICD-9-CM codes. Patients with equivalent numbers of codes for Crohn disease and UC were classified as having indeterminate colitis. Patients were included if ADA was the first anti-TNF prescribed during the time period studied and if they had 3 months of coverage prior to ADA initiation with no other anti-TNF prescriptions during that time. This 3-month window was created to ensure that patients were less likely to be on an anti-TNF prior to acquiring coverage in the VHA or MarketScan cohorts.

Patients with IBD in the VHA were identified using previously validated algorithms based on a combination of inpatient and outpatient ICD-9-CM codes for Crohn disease (555.X) and UC (556.X) between 2002 and 2014.15 Patients were required to have at least 2 encounters with a diagnosis of IBD, with at least 1 encounter as an outpatient. In this administrative cohort, this classification method for Crohn disease and UC has been studied and validated.16 Patients were classified as having Crohn disease if all ICD-9-CM codes were 555.X, UC if all codes were 556.X, and indeterminate colitis in the remainder. This approach has positive predictive values of 0.84 for Crohn disease and 0.91 for UC in the VHA.16 To be consistent with the date range of available data in MarketScan, only patients with their first prescribed anti-TNF between 2009 and 2013 were considered for inclusion, with follow-up until the conclusion of 2014. Due to a 75% smaller sample in the VHA, we included 1 extra year of data.

Selected Predictors

Pharmaceutical claims for each cohort were analyzed for dispenses of ADA. Erroneous claims, identified as those indicating that a quantity of 0 or less was dispensed, were excluded from analysis. Claims data indicating that unusual quantities of medication were dispensed were also deleted, based on the following criteria. For ADA, we expected to find no more than 6 syringes dispensed in 14 days during induction (ratio of 2.33 days/injection) and no less than 2 syringes dispensed in 30 days for maintenance (ratio of 15 days/injection). Any patients with ADA dispensing ratios of less than 2.33 days per injection or more than 15 days per injection were removed from the data set. Patients with fewer than 3 fills of the medication in the study period were also removed.

A medication possession ratio (MPR) was used to assess adherence for the first year during the maintenance dosing after the first month’s induction period. The MPR was calculated by summing the days of medication supplied and dividing by the sum of the days in the total refill intervals. Patients with an MPR above the 99th percentile (MPR >1.2) were deleted because those patient records were suspected to contain erroneous claims data. The MPR was therefore capped at 1.2. Based on prior studies that indicated an MPR for ADA of 0.86 was ideal to avoid complications, we classified patients as adherent if their MPR was over this value.17 We elected to include MPRs over 1 to allow capture of early refill data.17

We identified dose escalation of ADA by comparing prescriptions from the beginning of maintenance to the last prescription within the first year and identified any increase in the ratio of pens dispensed to days supplied. Concurrent medication usage (corticosteroids and immunomodulators) at study initiation was assessed by determining if there was use of either of these medications in the 90 days before or 30 days after starting ADA. The immunomodulators evaluated included thiopurines and methotrexate. Concurrent narcotic use at initiation was defined as a prescription in the 30 days prior to or 30 days post ADA initiation. A complete detailed list of concomitant medications evaluated is located in eAppendix Table 1 (eAppendix available at The effect of a disease flare on persistence was addressed by determining if a patient had a hospitalization or new corticosteroid prescription after starting ADA. In order to account for the effect of comorbidities on medication persistence, we calculated Charlson Comorbidity Index (CCI) scores during the 1 year prior to ADA initiation.18


The outcome measure of persistence was defined as continued filled prescription of ADA 1 year after initiation without an interruption of greater than 4 months. An interruption of 4 months was chosen due to the half-life of ADA, which is estimated at 10 to 20 days,19 and the fact that the medication is typically stopped perioperatively for lengthy periods of time.

Statistical Analysis

Descriptive statistics were used to compare the VHA and MarketScan populations. Two-sample t tests were used for continuous variables, and χ2 tests were used for categorical variables. The relationship of concomitant medication use, adherence, and demographic predictors with persistence was assessed within the 2 cohorts using multivariable logistic regression. The effect of adherence was assessed by classifying MPR as a binary variable using the 0.86 threshold for adherence, and odds ratios (ORs) for age were calculated per decade due to small effect size. Model parameters were assessed by type III χ2 tests, and P values and 95% CIs for ORs were constructed using Wald test specifications. Sensitivity analyses were conducted to determine if a standardized definition of IBD phenotype (Crohn disease vs UC) between the 2 cohorts had an effect on outcomes and if there was an interaction between dose escalation and immunomodulator use. All statistics were performed using SAS 9.4 (SAS Institute Inc; Cary, North Carolina).

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