Policy Options for Infliximab Biosimilars in Inflammatory Bowel Disease Given Emerging Evidence for Switching

Don Husereau, Brian Feagan, Carl Selya-Hammer, Don Husereau, Brian Feagan, Carl Selya-Hammer

Abstract

Biosimilars are becoming increasingly available internationally as patents expire on the originator biologic drugs they are intended to copy. Although substitution policies seen with generic drugs are being considered as a means to reduce expenditures on biologics, some biosimilars pose particular challenges in that the act of substitution may eventually lead to increased rates of therapeutic failure. As evidence requirements from regulators do not directly address this challenge, switch trials of biosimilars have emerged that may provide further answers. Using infliximab in inflammatory bowel disease as an example, we critically examine emerging evidence from two key switch trials (NOR-SWITCH and NCT020968610) and discuss the clinical and economic implications of these and what policy options may be most reasonable for payers. Options include reimbursing biosimilars for only newly diagnosed patients, using product-listing agreements to manage uncertainty, or using tiered co-payments or other incentives to promote biosimilar use.

Conflict of interest statement

Funding sources

All authors have received funding from Janssen/J&J for market access advice and analysis. DH has received funding to draft the manuscript and BF and DH have provided market access advice to the funder. CSH has provided market access advice and conducted the economic evaluation for the funder.

Author contributions

BF provided the original inspiration and some key content for this work. DH led the writing of the manuscript including the drafting of the outline and manuscript and is the guarantor of this work. All authors approved the outline of the work, helped to write and revise the manuscript, and read and approved the final version of the manuscript.

Conflict of interest

All authors have signed conflict of interest forms and read information regarding disclosure of potential conflict of interest at http://www.springer.com/us/authors-editors/journal-author/journal-author-helpdesk/before-you-start and declare the following: accepting consulting fees from medical device and pharmaceutical companies who may have interest in the work (DH, BF, CSH).

Figures

Fig. 1
Fig. 1
Forest plot of infliximab originator versus biosimilar from NOR-SWITCH indicating improvement or worsening in disease according to disease-specific instruments
Fig. 2
Fig. 2
Probabilistic sensitivity analysis scatterplot for biosimilar versus originator infliximab

References

    1. Declerck P, Danesi R, Petersel D, Jacobs I. The language of biosimilars: clarification, definitions, and regulatory aspects. Drugs. 2017;77:671–677. doi: 10.1007/s40265-017-0717-1.
    1. Manolis CH, Rajasenan K, Harwin W, et al. Biosimilars: opportunities to promote optimization through payer and provider collaboration. J Manag Care Spec Pharm. 2016;22:S3–S9. doi: 10.18553/jmcp.2016.22.9-a.s3.
    1. Simoens S. Biosimilar medicines and cost-effectiveness. Clinicoecon Outcomes Res. 2011;3:29–36. doi: 10.2147/CEOR.S12494.
    1. Gray T, Bertch K, Galt K, et al. Guidelines for therapeutic interchange-2004. Pharmacotherapy. 2005;25:1666–1680. doi: 10.1592/phco.2005.25.11.1666.
    1. Mills EJ, Gardner D, Thorlund K, et al. A users’ guide to understanding therapeutic substitutions. J Clin Epidemiol. 2014;67:305–313. doi: 10.1016/j.jclinepi.2013.09.008.
    1. Feagan BG, Choquette D, Ghosh S, et al. The challenge of indication extrapolation for infliximab biosimilars. Biologicals. 2014;42:177–183. doi: 10.1016/j.biologicals.2014.05.005.
    1. Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013;108:40–47. doi: 10.1038/ajg.2012.363.
    1. Bartelds GM, Krieckaert CLM, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305:1460–1468. doi: 10.1001/jama.2011.406.
    1. Hanauer SB, Wagner CL, Bala M, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:542–553. doi: 10.1016/S1542-3565(04)00238-1.
    1. Gentileschi S, Barreca C, Bellisai F, et al. Switch from infliximab to infliximab biosimilar: efficacy and safety in a cohort of patients with different rheumatic diseases. Response to: Nikiphorou E, Kautiainen H, Hannonen P, et al. Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther. 2015;15:1677–1683. doi: 10.1517/14712598.2015.1103733.
    1. Dranitsaris G, Jacobs I, Kirchhoff C, et al. Drug tendering: drug supply and shortage implications for the uptake of biosimilars. Clinicoecon Outcomes Res. 2017;9:573–584. doi: 10.2147/CEOR.S140063.
    1. Weise M, Kurki P, Wolff-Holz E, et al. Biosimilars: the science of extrapolation. Blood. 2014;124:3191–3196. doi: 10.1182/blood-2014-06-583617.
    1. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395. doi: 10.1056/NEJMoa0904492.
    1. Vermeire S, Noman M, Van Assche G, et al. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007;56:1226–1231. doi: 10.1136/gut.2006.099978.
    1. Gabbani T, Deiana S, Annese V. CT-P13: design, development, and place in therapy. Drug Des Dev Ther. 2017;11:1653–1661. doi: 10.2147/DDDT.S109852.
    1. Church PC, Guan J, Walters TD, et al. Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn’s disease. Inflamm Bowel Dis. 2014;20:1177–1186. doi: 10.1097/MIB.0000000000000083.
    1. Braun J, Kudrin A. Switching to biosimilar infliximab (CT-P13): evidence of clinical safety, effectiveness and impact on public health. Biologicals. 2016;44:257–266. doi: 10.1016/j.biologicals.2016.03.006.
    1. Vegh Z, Kurti Z, Lakatos PL. Real-life efficacy, immunogenicity and safety of biosimilar infliximab. DDI. 2017;35:101–106.
    1. Danese S, Fiorino G, Raine T, et al. ECCO position statement on the use of biosimilars for inflammatory bowel disease—an update. J Crohns Colitis. 2017;11:26–34. doi: 10.1093/ecco-jcc/jjw198.
    1. Martelli L, Peyrin-Biroulet L. Efficacy, safety and immunogenicity of biosimilars in inflammatory bowel diseases: a systematic review. Curr Med Chem. 2016;23. 10.2174/0929867323666161014153346. Available from: .
    1. The NOR-SWITCH Study—full text view— [Internet]. . Cited 6 Apr 2017.
    1. Jørgensen KK, Olsen IC, Goll GL, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389:2304–2316. doi: 10.1016/S0140-6736(17)30068-5.
    1. Demonstrate noninferiority in efficacy and to assess safety of CT-P13 in patients with active Crohn’s disease—full text view— [Internet]. . 21 Mar Cited 2017.
    1. Efficacy and safety of infliximab-biosimilar (Inflectra) compared to infliximab-innovator (Remicade) in patients with inflammatory bowel disease in remission: the SIMILAR Trial—full text view— [Internet]. . Cited 17 Oct 2017.
    1. Claxton K. The irrelevance of inference: a decision-making approach to the stochastic evaluation of health care technologies. J Health Econ. 1999;18:341–364. doi: 10.1016/S0167-6296(98)00039-3.
    1. Billmeier U, Dieterich W, Neurath MF, et al. Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases. World J Gastroenterol. 2016;22:9300–9313. doi: 10.3748/wjg.v22.i42.9300.
    1. Kim YH, Ye BD, Pesegova M, et al. Phase III randomized, double-blind, controlled trial to compare biosimilar infliximab (CT-P13) with innovator infliximab (INX) in patients with active Crohn’s disease: early efficacy and safety results. Gastroenterology. 2017;152:S65. doi: 10.1016/S0016-5085(17)30571-1.
    1. Danese S, Fiorino G, Michetti P. Changes in biosimilar knowledge among European Crohn’s colitis organization [ECCO] members: an updated survey. J Crohns Colitis. 2016;10:1362–1365. doi: 10.1093/ecco-jcc/jjw090.
    1. U.S. Department of Health and Human Services Food and Drug Administration. Considerations in demonstrating interchangeability with a reference product—DRAFT GUIDANCE. 2017.
    1. Government of Ontario M of H and L-TC. Exceptional access program—formulary—Health Care Professionals—MOHLTC [Internet]. . Cited 11 Jan 2018.
    1. Formulary Search—search results [Internet]. . Cited 11 Jan 2018
    1. Claxton K. The irrelevance of inference: a decision-making approach to the stochastic evaluation of health care technologies. J Health Econ. 1999;18:341–364. doi: 10.1016/S0167-6296(98)00039-3.
    1. Severens JL, Brunenberg DEM, Fenwick EAL, et al. Cost-effectiveness acceptability curves and a reluctance to lose. Pharmacoeconomics. 2005;23:1207–1214. doi: 10.2165/00019053-200523120-00005.
    1. O’Brien BJ, Gertsen K, Willan AR, et al. Is there a kink in consumers’ threshold value for cost-effectiveness in health care? Health Econ. 2002;11:175–180. doi: 10.1002/hec.655.
    1. Eckermann S. Kinky thresholds revisited: opportunity costs differ in the NE and SW quadrants. Appl Health Econ Health Policy. 2015;13:7–13. doi: 10.1007/s40258-014-0136-3.
    1. Mestre-Ferrandiz J, Towse A, Berdud M. Biosimilars: how can payers get long-term savings? Pharmacoeconomics. 2016;34:609–616. doi: 10.1007/s40273-015-0380-x.
    1. Happe LE, Clark D, Holliday E, et al. A systematic literature review assessing the directional impact of managed care formulary restrictions on medication adherence, clinical outcomes, economic outcomes, and health care resource utilization. JMCP. 2014;20:677–684. doi: 10.18553/jmcp.2014.20.7.677.
    1. Grabowski HG, Guha R, Salgado M. Regulatory and cost barriers are likely to limit biosimilar development and expected savings in the near future. Health Aff (Millwood) 2014;33:1048–1057. doi: 10.1377/hlthaff.2013.0862.
    1. Husereau D, Henshall C, Sampietro-Colom L, et al. Changing health technology assessment paradigms? Int J Technol Assess Health Care. 2016;32:191–199. doi: 10.1017/S0266462316000386.
    1. Update to guidelines for the economic evaluation of health technologies: Canada | [Internet]. . Cited 22 Mar 2017.
    1. Minghetti P, Rocco P, Schellekens H. The constrained prescription, interchangeability and substitution of biosimilars. Nat Biotechnol. 2015;33:688–689. doi: 10.1038/nbt.3272.
    1. Paris V, Docteur E. Pharmaceutical pricing and reimbursement policies in Canada. [Internet]. Paris: organisation for economic co-operation and development. 2006. .
    1. NPDUIS CompassRx, 3rd edition—2015/16 [Internet]. 2017. . Cited 17 Jan 2018.
    1. Beilman CL, Ma C, McCabe C, et al. Cost-effectiveness of infliximab’s biosimilar CT-P13 compared to innovator infliximab for the management of Crohn’s disease. Gastroenterology. 2017;152:S447. doi: 10.1016/S0016-5085(17)31702-X.
    1. Berntgen M, Gourvil A, Pavlovic M, et al. Improving the contribution of regulatory assessment reports to health technology assessments—a collaboration between the European medicines agency and the European network for health technology assessment. Value Health. 2014;17:634–641. doi: 10.1016/j.jval.2014.04.006.
    1. Henshall C, Mardhani-Bayne L, Frønsdal KB, et al. Interactions between health technology assessment, coverage, and regulatory processes: emerging issues, goals, and opportunities. Int J Technol Assess Health Care. 2011;27:253–260. doi: 10.1017/S0266462311000262.
    1. Chen YHJ, Chen C. Testing superiority at interim analyses in a non-inferiority trial. Stat Med. 2012;31:1531–1542. doi: 10.1002/sim.5312.
    1. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16:231–250. doi: 10.1016/j.jval.2013.02.002.
    1. Bodger K, Kikuchi T, Hughes D. Cost-effectiveness of biological therapy for Crohn’s disease: Markov cohort analyses incorporating United Kingdom patient-level cost data. Aliment Pharmacol Ther. 2009;30:265–274. doi: 10.1111/j.1365-2036.2009.04033.x.
    1. Hodgson R, Walton M, Biswas M, et al. Ustekinumab for treating moderately to severely active Crohn’s disease after prior therapy: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics. 2017

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit