Background: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use. Conclusions: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics.

Keywords:
Biosimilars, Infliximab, Inflammatory bowel disease, Crohns disease, Ulcerative colitis, Health economics
1.
Lennard-Jones JE: Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl 1989;170:2-6; discussion 16-19.
2.
Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al: Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142:46-54.e42; quiz e30.
3.
Burisch J, Pedersen N, Čuković-Čavka S, Brinar M, Kaimakliotis I, Duricova D, et al: East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut 2014;63:588-597.
4.
Loftus CG, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ 3rd, et al: Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis 2007;13:254-261.
5.
Bernstein CN, Wajda A, Svenson LW, MacKenzie A, Koehoorn M, Jackson M, et al: The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am J Gastroenterol 2006;101:1559-1568.
6.
Perminow G, Frigessi A, Rydning A, Nakstad B, Vatn MH: Incidence and clinical presentation of IBD in children: comparison between prospective and retrospective data in a selected Norwegian population. Scand J Gastroenterol 2006;41:1433-1439.
7.
Satsangi J, Silverberg MS, Vermeire S, Colombel JF: The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006;55:749-753.
8.
Larsen S, Bendtzen K, Nielsen OH: Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 2010;42:97-114.
9.
Moum B, Vatn MH, Ekbom A, Aadland E, Fausa O, Lygren I, et al: Incidence of ulcerative colitis and indeterminate colitis in four counties of southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists. Scand J Gastroenterol 1996;31:362-366.
10.
Moum B, Vatn MH, Ekbom A, Aadland E, Fausa O, Lygren I, et al: Incidence of Crohn's disease in four counties in southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists. Scand J Gastroenterol 1996;31:355-361.
11.
Solberg IC, Cvancarova M, Vatn MH, Moum B: Risk matrix for prediction of advanced disease in a population-based study of patients with Crohn's Disease (the IBSEN Study). Inflamm Bowel Dis 2014;20:60-68.
12.
Moum B, Hovde O, Hoivik ML: What have we learnt about the role of the environment and natural course of IBD in the new millennium? 20-year follow-up of the IBSEN cohort. Dig Dis 2014;32(suppl 1):2-9.
13.
Solberg IC, Hoivik ML, Cvancarova M, Moum B: Risk matrix model for prediction of colectomy in a population-based study of ulcerative colitis patients (the IBSEN study). Scand J Gastroenterol 2015;50:1456-1462.
14.
Abraham C, Cho JH: Inflammatory bowel disease. N Engl J Med 2009;361:2066-2078.
15.
Sartor RB: Microbial influences in inflammatory bowel diseases. Gastroenterology 2008;134:577-594.
16.
Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY, Keller BC, et al: Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 2015;160:447-460.
17.
Lichtenstein GR, Abreu MT, Cohen R, Tremaine W: American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006;130:940-987.
18.
Hoivik ML, Moum B, Solberg IC, Henriksen M, Cvancarova M, Bernklev T: Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study. Gut 2013;62:368-375.
19.
DeVries JH, Gough SC, Kiljanski J, Heinemann L: Biosimilar insulins: a European perspective. Diabetes Obes Metab 2015;17:445-451.
20.
Rutgeerts P, Vermeire S, Van Assche G: Biological therapies for inflammatory bowel diseases. Gastroenterology 2009;136:1182-1197.
21.
Cote-Daigneault J, Bouin M, Lahaie R, Colombel JF, Poitras P: Biologics in inflammatory bowel disease: what are the data? United European Gastroenterol J 2015;3:419-428.
22.
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476.
23.
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al: Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-1549.
24.
Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, et al: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010;362:1383-1395.
26.
Crommelin DJ, Storm G, Verrijk R, de Leede L, Jiskoot W, Hennink WE: Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharm 2003;266:3-16.
27.
European Medicines Agency: Committee for Medicinal Products for Human Use. Assessment Report. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Public_assessment_report/human/002778/WC500151490.pdf (cited December 11, 2015).
28.
Park W, Hrycaj P, Jeka S, Kovalenko V, Lysenko G, Miranda P, et al: A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605-1612.
29.
Yoo DH, Hrycaj P, Miranda P, Ramiterre E, Piotrowski M, Shevchuk S, et al: A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613-1620.
30.
Jung YS, Park DI, Kim YH, Lee JH, Seo PJ, Cheon JH, et al: Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: a retrospective multicenter study. J Gastroenterol Hepatol 2015;30:1705-1712.
31.
Farkas K, Rutka M, Balint A, Nagy F, Bor R, Milassin A, et al: Efficacy of the new infliximab biosimilar CT-P13 induction therapy in Crohn's disease and ulcerative colitis - experiences from a single center. Expert Opin Biol Ther 2015;15:1257-1262.
32.
Gecse KB, Lovasz BD, Farkas K, Banai J, Bene L, Gasztonyi B, et al: Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: a prospective, multicentre, nationwide cohort. J Crohns Colitis 2016;10:133-140.
33.
Jahnsen J, Detlie TE, Vatn S, Ricanek P: Biosimilar infliximab (CT-P13) in the treatment of inflammatory bowel disease: a Norwegian observational study. Expert Rev Gastroenterol Hepatol 2015;9(suppl 1):45-52.
34.
Sieczkowska J, Jarzebicka D, Banaszkiewicz A, Plocek A, Gawronska A, Toporowska-Kowalska E, et al: Switching between infliximab originator and biosimilar in paediatric patients with inflammatory bowel disease. Preliminary observations. J Crohns Colitis 2016;10:127-132.
35.
Miheller P, Lakatos PL, Horvath G, Molnar T, Szamosi T, Czegledi Z, et al: Efficacy and safety of infliximab induction therapy in Crohn's disease in central Europe -a Hungarian nationwide observational study. BMC Gastroenterol 2009;9:66.
36.
Gecse KB, Lovasz BD, Farkas K, Banai J, Bene L, Gasztonyi B, et al: Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: a prospective, multicentre, nationwide cohort. J Crohns Colitis 2016;10:133-140.
38.
Panaccione R, Ghosh S, Middleton S, Marquez JR, Scott BB, Flint L, et al: Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014;146:392-400.e3.
39.
Lee KM, Jeen YT, Cho JY, Lee CK, Koo JS, Park DI, et al: Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: a Korean multicenter retrospective study. J Gastroenterol Hepatol 2013;28:1829-1833.
40.
Ben-Horin S, Heap GA, Ahmad T, Kim H, Kwon T, Chowers Y: The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications? Expert Rev Gastroenterol Hepatol 2015;9(suppl 1):27-34.
41.
Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, et al: Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001;98:3241-3248.
42.
Danese S, Fiorino G, Michetti P: Viewpoint: knowledge and viewpoints on biosimilar monoclonal antibodies among members of the European Crohn's and Colitis Organization. J Crohns Colitis 2014;8:1548-1550.
43.
Gomollon F: Biosimilars: are they bioequivalent? Dig Dis 2014;32(suppl 1):82-87.
44.
Gibson TB, Ng E, Ozminkowski RJ, Wang S, Burton WN, Goetzel RZ, et al: The direct and indirect cost burden of Crohn's disease and ulcerative colitis. J Occup Environ Med 2008;50:1261-1272.
45.
Stark R, Konig HH, Leidl R: Costs of inflammatory bowel disease in Germany. Pharmacoeconomics 2006;24:797-814.
46.
Blomqvist P, Ekbom A: Inflammatory bowel diseases: health care and costs in Sweden in 1994. Scand J Gastroenterol 1997;32:1134-1139.
47.
Odes S, Greenberg D: A medicoeconomic review of early intervention with biologic agents in the treatment of inflammatory bowel diseases. Clinicoecon Outcomes Res 2014;6:431-443.
48.
Bernstein CN, Ng SC, Lakatos PL, Moum B, Loftus EV Jr: A review of mortality and surgery in ulcerative colitis: milestones of the seriousness of the disease. Inflamm Bowel Dis 2013;19:2001-2010.
49.
Bernstein CN, Loftus EV Jr, Ng SC, Lakatos PL, Moum B: Hospitalisations and surgery in Crohn's disease. Gut 2012;61:622-629.
50.
van der Valk ME, Mangen MJ, Leenders M, Dijkstra G, van Bodegraven AA, Fidder HH, et al: Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study. Gut 2014;63:72-79.
51.
Moum B: Sykehus- og pasientadministrert biologisk behandling av inflammatorisk tarmsykdom - årlige ressurser og kostnader. 2015. https://bestprac.no/Default.aspx?ID=548&GroupID=GROUP540.
52.
Putrik P, Ramiro S, Keszei AP, Hmamouchi I, Dougados M, Uhlig T, et al: Lower education and living in countries with lower wealth are associated with higher disease activity in rheumatoid arthritis: results from the multinational COMORA study. Ann Rheum Dis 2016;75:540-546.
53.
Putrik P, Ramiro S, Kvien TK, Sokka T, Pavlova M, Uhlig T, et al: Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis 2014;73:198-206.
54.
Putrik P, Ramiro S, Kvien TK, Sokka T, Uhlig T, Boonen A: Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis 2014;73:2010-2021.
55.
Gomollon F: Biosimilars in inflammatory bowel disease: ready for prime time? Curr Opin Gastroenterol 2015;31:290-295.
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