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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.
DISCUSSION

In this analysis of anti-TNF persistence in 2 large administrative databases, we found that patients with IBD initiated on ADA had an approximately 60% likelihood of remaining on the drug at 1 year without an interruption of more than 4 months. The persistence rate among the veteran population was higher at 73% versus 55% in the privately insured cohort. We found expected differences in demographics between the MarketScan and the veteran population but also found differences in concomitant medications at ADA initiation. We also identified that patients who were on narcotics or had a flare (assessed through a hospitalization or new steroid use) in the MarketScan cohort were significantly less likely to remain on ADA 1 year later. Although we could not assess for ADA drug levels, we did identify that patients who underwent dose escalation or were more adherent were also more likely to be persistent in the MarketScan cohort.

Unexpectedly, we did not find a relationship between concomitant immunomodulator use and persistence. In a cohort study by Targownik et al of Canadian patients with IBD started on anti-TNFs, 60% of patients remained on the anti-TNF at the 1-year mark.20 In another cohort study, of veterans taking anti-TNFs in the United States, 24% were no longer taking the medication at the 6-month time point.7 In both of these studies, concurrent immunomodulator use was found to be a predictor of continued drug use. Concurrent immunomodulator use has been shown to lead to beneficial outcomes in clinical trials and clinical practice,4,21 and it is hypothesized that persistence is improved due to reduced levels of antidrug antibodies and/or increased drug levels.22 In our much larger study, although results showed that concurrent immunomodulator use did not influence continued anti-TNF use, we found that anti-TNF dose escalation was in fact associated with persistence in the MarketScan cohort. We speculate that immunomodulator use was not associated with ADA persistence here either due to insufficient dosing of the immunomodulator or poor adherence to the immunomodulator. The effect of an interaction term between escalation of ADA and immunomodulator use was found to be not significant when added to the model, and the estimated effect of immunomodulator use did not change when escalation was dropped from the model as a sensitivity analysis. Overall, we can conclude in our study that immunomodulator use did not affect persistence.

Despite higher ADA persistence in the VHA cohort, we saw similar rates of hospitalization and steroid use within 1 year between the 2 cohorts. This finding is more remarkable considering that the VHA has an older patient population with more comorbidities. Although ADA persistence is higher in the VHA system, patients in the VHA had slightly lower adherence rates. Because this is a review of administrative data, it is difficult to ascertain why persistence but not adherence is better in the VHA compared with outside health systems. Other comparisons of VHA versus non-VHA care have identified higher quality of care delivery in the VHA system,23 which may be one reason. We hypothesize that the VHA population has superior ADA persistence due to the combination of an integrated pharmacy system and improved provider communication. There may be other reasons for increased persistence in the VHA population, including disease severity, which we were unable to quantify in this study.

A number of studies have identified that narcotic use is high in the IBD population.24-26 Narcotic use has also been linked with increased costs and worse postoperative outcomes.27,28 Despite increasing use of anti-TNFs, narcotic use appears to be stable in the IBD population.25 Our findings here show that narcotic use was also independently associated with reduced chances of remaining on the anti-TNF at 1 year in the MarketScan cohort. Narcotic use was particularly prevalent in our study, at 20% to 27% (MarketScan and VHA, respectively) around the time of anti-TNF start. This prevalence was similar to the overall prevalence noted in a single-center study.24 Systematic changes are under way to reduce narcotic prescriptions in the United States. Further studies will need to be conducted to determine if this improves anti-TNF persistence.

Limitations

The limitations of our study include the reliance on administrative claims data, which are susceptible to errors. To correct for possible errors, we removed patients who had fills of ADA that appeared erroneous based on the ratio of intended days’ supply and quantity of injections. Prescriptions with fewer than 2.3 days between injections or more than 15 days per injection were labeled as erroneous. The results of the multivariate analysis in the VHA cohort are limited by sample size, and some significant predictors seen in the MarketScan cohort appear as trends in the same direction in the VHA cohort. We used 2 definitions to classify patients into IBD phenotypes, but we also performed a sensitivity analysis that demonstrated that using consistent diagnosis codes did not change our main findings. The methodology used to classify the VHA patients has been validated in that cohort.16 There is no validated methodology to classify patients in the private insurance database we used, so we elected to use a methodology previously published for this insurance database and other large insurance databases.29 The results of the VHA cohort analysis are not likely generalizable to other US cohorts. This is corroborated by the demographic differences, as well as the medication use differences, between the 2 cohorts. It is possible that VHA patients could obtain medications outside of the VHA, but it is more likely that this occurred with the concomitant medications rather than ADA because the cost of this medication is considerably cheaper in the VHA. Other predictors of adherence were not accounted for in our analysis, including specialty pharmacy dispensation versus commercial pharmacy dispensation.30 We elected not to perform statistical comparisons between the 2 cohorts because there were small differences in the definitions used to characterize the 2 cohorts and 1 extra year of analyzed data in the VHA cohort, which may have invalidated these comparisons.

CONCLUSIONS

Persistence with ADA in 2 large IBD cohorts in the United States is approximately 60%. Patients receiving healthcare through a publicly funded integrated healthcare system appeared to have a higher rate of persistence compared with privately insured patients. Patients in a privately insured cohort who were more adherent or underwent dose escalation were more likely to remain on the drug, whereas concomitant immunomodulator use was not noted to have an effect on persistence. Concomitant narcotic use at anti-TNF start was independently associated with a reduced chance of continued use at 1 year. Further studies to identify systemwide differences are necessary to understand the differences in ADA persistence between the 2 cohorts, and it is crucial to focus more efforts on reducing the use of corticosteroids and narcotics in these populations.

Author Affiliations: South Texas Veterans Health Care System (SMG, JAP), San Antonio, TX; Department of Internal Medicine (SMG, JAP) and Department of Psychiatry (DIV), UT Health San Antonio, San Antonio, TX; Department of Internal Medicine, University of Michigan (SMG, MN, PDRH, SDS, RWS, AKW), Ann Arbor, MI; Center for Clinical Management Research (RL, WW, SDS, AKW), Ann Arbor, MI.

Source of Funding: None.

Author Disclosures: Dr Higgins received a grant from AbbVie (manufacturer of adalimumab) to study the Fitbit Charge HR biometrics in the detection of inflammatory bowel disease flares, which was not connected to adalimumab. Dr Stidham reports a consultancy for AbbVie unrelated to this work. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (SMG, MN, PDRH, RWS, AKW); acquisition of data (MN, AKW); analysis and interpretation of data (SMG, RL, MN, WW, PDRH, SDS, JAP, DIV, RWS, AKW); drafting of the manuscript (SMG, RL, WW, SDS, JAP, DIV, AKW); critical revision of the manuscript for important intellectual content (SMG, RL, WW, PDRH, SDS, JAP, DIV, RWS, AKW); statistical analysis (SMG, RL, MN, WW, PDRH, AKW); and supervision (SMG, WW).

Address Correspondence to: Shail M. Govani, MD, MSc, South Texas Veterans Health Care System, 7400 Merton Minter Blvd, Mail Code 111D, San Antonio, TX 78229. Email: shail.govani@va.gov.
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