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IIR 19-045 – HSR Study

IIR 19-045
Effectivenes, Safety, and Patient Preferences of Infliximab Biosimilar Medications for Inflammatory Bowel Disease
Jason Hou, MD
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, TX
Akbar Waljee MD MSc
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, MI
Funding Period: February 2020 - September 2024


Background: Biologic medications (biologics) are highly effective for diseases of the immune system, cancers, and other conditions; however, their high expense is a barrier to care and a burden to the healthcare system. Biologics cannot be exactly copied as “generic” medications. Biosimilars- similar, but not identical versions of biologic medications- are approved with large potential cost savings. However, VA providers and patients have concerns regarding biosimilar switching safety and effectiveness as disease-specific randomized controlled trials are not required for approval. Significance/Impact: Antagonists to tumor necrosis factor-α (Anti-TNFs) are the largest class of biologics with biosimilars where switching may be feasible to reduce costs; however how to safely and effectively integrate their use in a manner acceptable to patients is unknown. This proposal addresses the VA HSR priority of veteran safety, the ORD-wide research priority of increasing substantial real- world impact of VA research, and uses cross-cutting HSR methods of health systems engineering through a learning healthcare system. Innovation: Crohn’s disease (CD) and ulcerative colitis (UC) are the 1st and 2nd most common indications for Anti-TNFs in the VA and can serve as a model for a learning healthcare system approach for mitigation of adverse events related to biosimilar switching. Specific Aims: Aim 1a: To compare rates of adverse events in CD and UC patients continued on Anti-TNF originator to those switched to biosimilar. Aim 1b: To compare rates of CD or UC exacerbation in patients continued on Anti-TNF originator to those switched to biosimilar. Aim 2: To compare the accuracy and calibration of 2a) traditional regression models vs. 2b) machine learning models for predicting medication related adverse event related to Anti-TNF in VA users with CD and UC. Aim 3: To use deliberative democracy methods to engage Veterans, to elicit their preference regarding “like" medication switch programs with and without their knowledge and to develop consensus around treatment approaches. Methodology: Aim 1 will be achieved through a retrospective cohort study of CD and UC patients who received Anti-TNF from the national VA datasets from 2017-2019. Adverse events and exacerbations will be determined using a combination of administrative data and manual chart review. Analyses for Aim 1 will proceed by Poisson regression using GEE. Adjusted event rate ratios of patients switched to biosimilar compared to those who continued on originator biosimilar will be calculated with 95% confidence intervals and Wald p-values will be derived from the regression model estimates. Prediction of patients who have adverse events to Anti-TNF will inform selection of appropriate therapy, and guidance of patients for biosimilar switching. For Aim 2, both traditional regression models and machine learning models will be constructed to identify which model will be better for predicting Anti-TNF related adverse events. Developing the best possible risk stratification tool by comparing these models will allow us to identify veterans that are at risk of adverse events to improve both the quality and efficiency of veteran care. It is critically important that VA policies incorporate the opinions of Veterans on ethically controversial issues that impact their health. Aim 3 will employ deliberative democratic methods that offer a practical and reliable approach to soliciting informed and considered opinions in complex policy issues. Democratic deliberation uses education by experts and carefully structured deliberation among peers to deliver informed opinions and policy suggestions from concerned stakeholders. Next Steps/ Implementation: This proposal is supported with clinical partners: the national VA Inflammatory Bowel Disease Technical Advisory Group and Pharmacy Benefits Management who will disseminate findings from this study through VA-specific biosimilar switch clinical guidelines and VA-pharmacy prescription policy. Future studies will include pragmatic clinical trials of other biosimilar biologics using the learning healthcare platform created in this proposal.

External Links for this Project

NIH Reporter

Grant Number: I01HX003028-01

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Journal Articles

  1. Elmunzer BJ, Wolf BJ, Scheiman JM, Tierney WM, Taylor JR, North American Alliance for the Study of Digestive Manifestations of COVID-19. Association Between Preadmission Acid Suppressive Medication Exposure and Severity of Illness in Patients Hospitalized With COVID-19. Gastroenterology. 2021 Mar 1; 160(4):1417-1422.e14. [view]
  2. Cohen-Mekelburg S, Wallace BI, Van T, Wiitala WL, Govani SM, Burns J, Lipson R, Yun H, Hou J, Lewis JD, Dominitz JA, Waljee AK. Association of Anti-Tumor Necrosis Factor Therapy With Mortality Among Veterans With Inflammatory Bowel Disease. JAMA Network Open. 2021 Mar 1; 4(3):e210313. [view]
  3. Cohen-Mekelburg S, Berry S, Stidham RW, Zhu J, Waljee AK. Clinical applications of artificial intelligence and machine learning-based methods in inflammatory bowel disease. Journal of gastroenterology and hepatology. 2021 Feb 1; 36(2):279-285. [view]
  4. Valley TS, Kamdar N, Wiitala WL, Ryan AM, Seelye SM, Waljee AK, Nallamothu BK. Continuous quality improvement in statistical code: avoiding errors and improving transparency. BMJ quality & safety. 2021 Mar 1; 30(3):240-244. [view]
  5. Elmunzer BJ, Spitzer RL, Foster LD, Merchant AA, Howard EF, Patel VA, West MK, Qayed E, Nustas R, Zakaria A, Piper MS, Taylor JR, Jaza L, Forbes N, Chau M, Lara LF, Papachristou GI, Volk ML, Hilson LG, Zhou S, Kushnir VM, Lenyo AM, McLeod CG, Amin S, Kuftinec GN, Yadav D, Fox C, Kolb JM, Pawa S, Pawa R, Canakis A, Huang C, Jamil LH, Aneese AM, Glamour BK, Smith ZL, Hanley KA, Wood J, Patel HK, Shah JN, Agarunov E, Sethi A, Fogel EL, McNulty G, Haseeb A, Trieu JA, Dixon RE, Yang JY, Mendelsohn RB, Calo D, Aroniadis OC, LaComb JF, Scheiman JM, Sauer BG, Dang DT, Piraka CR, Shah ED, Pohl H, Tierney WM, Mitchell S, Condon A, Lenhart A, Dua KS, Kanagala VS, Kamal A, Singh VK, Pinto-Sanchez MI, Hutchinson JM, Kwon RS, Korsnes SJ, Singh H, Solati Z, Willingham FF, Yachimski PS, Conwell DL, Mosier E, Azab M, Patel A, Buxbaum J, Wani S, Chak A, Hosmer AE, Keswani RN, DiMaio CJ, Bronze MS, Muthusamy R, Canto MI, Gjeorgjievski VM, Imam Z, Odish F, Edhi AI, Orosey M, Tiwari A, Patwardhan S, Brown NG, Patel AA, Ordiah CO, Sloan IP, Cruz L, Koza CL, Okafor U, Hollander T, Furey N, Reykhart O, Zbib NH, Damianos JA, Esteban J, Hajidiacos N, Saul M, Mays M, Anderson G, Wood K, Mathews L, Diakova G, Caisse M, Wakefield L, Nitchie H, Waljee AK, Tang W, Zhang Y, Zhu J, Deshpande AR, Rockey DC, Alford TB, Durkalski V, North American Alliance for the Study of Digestive Manifestations of COVID-19. Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Jul 1; 19(7):1355-1365.e4. [view]
  6. Yao H, Najarian K, Gryak J, Bishu S, Rice MD, Waljee AK, Wilkins HJ, Stidham RW. Fully automated endoscopic disease activity assessment in ulcerative colitis. Gastrointestinal endoscopy. 2021 Mar 1; 93(3):728-736.e1. [view]
  7. Piper MS, Zikmund-Fisher BJ, Maratt JK, Kurlander J, Metko V, Waljee AK, Saini SD. Patients' Willingness to Share Limited Endoscopic Resources: A Brief Report on the Results of a Large Regional Survey. MDM policy & practice. 2021 Sep 28; 6(2):23814683211045648. [view]
  8. Hollingsworth JM, Yu X, Yan PL, Yoo H, Telem DA, Yankah EN, Zhu J, Waljee AK, Nallamothu BK. Provider Care Team Segregation and Operative Mortality Following Coronary Artery Bypass Grafting. Circulation. Cardiovascular quality and outcomes. 2021 May 1; 14(5):e007778. [view]
  9. Pham C, Tomcsanyi KM, Waljee AK, Hou JK. Re: Lin I, Melsheimer R, Bhak RH, et al. Impact of switching to infliximab biosimilars on treatment patterns among US veterans receiving innovator infliximab. Curr Med Res Opin. 2022;38(4):613-627. Current Medical Research and Opinion. 2022 Dec 1; 38(12):2241-2242. [view]
  10. Berinstein JA, Sheehan JL, Dias M, Berinstein EM, Steiner CA, Johnson LA, Regal RE, Allen JI, Cushing KC, Stidham RW, Bishu S, Kinnucan JAR, Cohen-Mekelburg SA, Waljee AK, Higgins PDR. Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Oct 1; 19(10):2112-2120.e1. [view]

DRA: Digestive Diseases
DRE: Treatment - Observational, TRL - Applied/Translational
Keywords: Patient Preferences, Patient Safety, Pharmacology
MeSH Terms: None at this time.

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