Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 8/2020

Open Access 01-08-2020 | Infliximab | Original Article

Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease

Authors: Edmond-Jean Bernard, Richard N. Fedorak, Vipul Jairath

Published in: Digestive Diseases and Sciences | Issue 8/2020

Login to get access

Abstract

Background and Aims

Biosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn’s disease (CD), has reduced direct drug costs. Though clinicians are comfortable with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13.

Methods

A literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance.

Results

A total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects.

Conclusions

The majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.
Literature
1.
Lybecker K. The Biologics Revolution in the Production of Drugs. Fraser Institute; 2016.
2.
Remicade Product Monograph. Beerse: Janssen Inc.; 2018.
3.
Lindsley CW. New 2016 Data and Statistics for global pharmaceutical products and projections through 2017. ACS Chem Neurosci. 2017;8:1635–1636.CrossRef
4.
Larsen L, Drewes AM, Broberg MCH, et al. Changing infliximab prescription patterns in inflammatory bowel disease: a population-based cohort study, 1999–2014. Inflamm Bowel Dis. 2018;24:433–439.CrossRef
5.
Yu H, MacIsaac D, Wong JJ, et al. Market share and costs of biologic therapies for inflammatory bowel disease in the USA. Aliment Pharmacol Ther. 2018;47:364–370.CrossRef
6.
Rubin DT, Mody R, Davis KL, Wang CC. Real-world assessment of therapy changes, suboptimal treatment and associated costs in patients with ulcerative colitis or Crohn’s disease. Aliment Pharmacol Ther. 2014;39:1143–1155.CrossRef
7.
Rocchi A, Benchimol EI, Bernstein CN, et al. Inflammatory bowel disease: a Canadian burden of illness review. Can J Gastroenterol. 2012;26:811–817.CrossRef
8.
9.
Malik AN, Cox J, Keeping K. Will U.S. payers champion biosimilars? Value Health. 2015;18:A265.CrossRef
10.
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.CrossRef
11.
Jørgensen KK, et al. Biosimilar infliximab (CT-P13) is not inferior to originator infliximab: explorative IBD subgroup analysis in Crohn’s disease and ulcerative colitis from the NOR-SWITCH trial [DDW Abstract 249]. Presented at: Digestive Disease Week Annual Meeting, May 6–9, 2017, Chicago, Illinois.
12.
Jørgensen KK, Goll GL, Sexton J, et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: explorative subgroup analyses in IBD from the NOR-SWITCH EXTENSION trial [ECCO Abstract P483]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
13.
Kim YH, Ye BD, Pesegova M, et al. Phase III randomized, double blind, controlled trial to compare biosimilar infliximab (CT-P13) with innovator infliximab in patients with active Crohn’s disease: early efficacy and safety results [DDW Abstract 248]. Presented at: Digestive Disease Week Annual Meeting, May 6–9, 2017, Chicago, Illinois.
14.
Volkers AG, Jansen JM. SIMILAR trial—Efficacy of infliximab-biological in patients with inflammatory bowel disease in remission—a randomized controlled, double blind, phase 4 non-inferiority trial [UEGW Abstract P0409]. United Eur Gastroenterol J. 2017;5:A307.
15.
Strik AS, van de Vrie W, Bloemsaat-Minekus JPJ, et al. Serum concentrations after switching from originator infliximab to the biosimilar CT-P13 in patients with quiescent inflammatory bowel disease (SECURE): an open-label, multicentre, phase 4 non-inferiority trial. Lancet Gastroenterol Hepatol. 2018;3:404–412.CrossRef
16.
Sieczkowska J, Jarzebicka D, Banaszkiewicz A, et al. Switching between infliximab originator and biosimilar in paediatric patients with inflammatory bowel disease. preliminary observations. J Crohns Colitis. 2016;10:127–132.CrossRef
17.
Park SH, Kim YH, Lee JH, et al. Post-marketing study of biosimilar infliximab (CT-P13) to evaluate its safety and efficacy in Korea. Expert Rev Gastroenterol Hepatol. 2015;9:35–44.CrossRef
18.
19.
Jung YS, Park DI, Kim YH, 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.CrossRef
20.
Arguelles-Arias F, Guerra Veloz MF, Perea Amarillo R, et al. Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results. Eur J Gastroenterol Hepatol. 2017;29:1290–1295.CrossRef
21.
Schmitz EMH, Boekema PJ, Straathof JWA, et al. Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12-month multicentre observational prospective cohort study. Aliment Pharmacol Ther. 2018;47:356–363.CrossRef
22.
Ratnakumaran R, To N, Gracie DJ, et al. Efficacy and tolerability of initiating, or switching to, infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD): a large single-centre experience. Scand J Gastroenterol. 2018;53:700–707.CrossRef
23.
Guerrero Puente L, Iglesias Flores E, Benitez JM, et al. Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. Gastroenterol Hepatol. 2017;40:595–604.CrossRef
24.
Fiorino G, Manetti N, Armuzzi A, et al. The PROSIT-BIO cohort: a prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar. Inflamm Bowel Dis. 2017;23:233–243.CrossRef
25.
Binkhorst L, Sobels A, Stuyt R, Westerman EM, West RL. Switching to a infliximab biosimilar: short-term results of clinical monitoring in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2018;30:699–703.CrossRef
26.
Smits LJT, Grelack A, Derikx L, et al. Long-term clinical outcomes after switching from Remicade((R)) to biosimilar CT-P13 in inflammatory bowel disease. Dig Dis Sci. 2017;62:3117–3122.CrossRef
27.
Smits LJ, Derikx LA, de Jong DJ, et al. Clinical outcomes following a switch from Remicade(R) to the biosimilar CT-P13 in inflammatory bowel disease patients: a prospective observational cohort study. J Crohns Colitis. 2016;10:1287–1293.CrossRef
28.
Razanskaite V, Bettey M, Downey L, et al. Biosimilar infliximab in inflammatory bowel disease: outcomes of a managed switching programme. J Crohns Colitis. 2017;11:690–696.PubMed
29.
Kang B, Lee Y, Lee K, Choi YO, Choe YH. Long-term outcomes after switching to CT-P13 in pediatric-onset inflammatory bowel disease: a single-center prospective observational study. Inflamm Bowel Dis. 2018;24:607–616.CrossRef
30.
Buer LC, Moum BA, Cvancarova M, Warren DJ, Medhus AW, Hoivik ML. Switching from Remicade(R) to Remsima(R) is well tolerated and feasible: a prospective, open-label study. J Crohns Colitis. 2017;11:297–304.CrossRef
31.
Avouac J, Molto A, Abitbol V, et al. Systematic switch from innovator infliximab to biosimilar infliximab in inflammatory chronic diseases in daily clinical practice: the experience of Cochin University Hospital, Paris, France. Semin Arthritis Rheum. 2018;47:741–748.CrossRef
32.
Kolar M, Duricova D, Bortlik M, et al. Infliximab biosimilar (Remsima) in therapy of inflammatory bowel diseases patients: experience from one tertiary inflammatory bowel diseases centre. Dig Dis. 2017;35:91–100.CrossRef
33.
Fiorino G, Ruiz-Arguello MB, Maguregui A, et al. Full Interchangeability in regard to immunogenicity between the infliximab reference biologic and biosimilars CT-P13 and SB2 in inflammatory bowel disease. Inflamm Bowel Dis. 2018;24:601–606.CrossRef
34.
Eberl A, Huoponen S, Pahikkala T, Blom M, Arkkila P, Sipponen T. Switching maintenance infliximab therapy to biosimilar infliximab in inflammatory bowel disease patients. Scand J Gastroenterol. 2017;52:1348–1353.CrossRef
35.
36.
Bettey M, Downey L, Underhill C, et al. Outcomes of a managed switching programme changing IBD patients on established originator infliximab to biosimilar infliximab. [ECCO Abstract DOP029]. Presented at: 11th Congress of ECCO, March 19–19, 2016, Amsterdam, Netherlands.
37.
Choe YH, Lee SH, Park DI, et al. Effectiveness and safety in Crohn’s disease patients who were treated with CT-P13 [ECCO Abstract P500]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
38.
Choe YH, Yang HR, Moon JS, et al. Effectiveness and safety of CT-P13 under routine care in paediatric patients with inflammatory bowel disease. [ECCO Abstract P487]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
39.
Daperno M, Guiotto C, Italia A, et al. Switching from infliximab originator to a first biosimilar is safe and effective: a single-centre series with through levels and anti-drug antibodies determination [ECCO Abstract P588]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
40.
Díaz Hernández L, Rodriguez González GE, Vela González M, et al. Efficacy and safety of switching between originator and biosimilar infliximab in patients with inflammatory bowel disease in practical clinic: results to 6 months [ECCO Abstract P449]. Presented at: 11th Congress of ECCO, March 19–19, 2016, Amsterdam, Netherlands.
41.
Guerra Veloz MF, Arguelles-Arias F, Perea Amarillo R, et al. Safety and efficacy of infliximab biosimilar (Remsima) in ulcerative colitis disease patients in clinical practice: results after 6-months treatment [ECCO Abstract P600]. Presented at: 11th Congress of ECCO, March 19–19, 2016, Amsterdam, Netherlands.
42.
Guerra Veloz MF, Arguelles-Arias F, Perea Amarillo R, et al. Safety and efficacy of infliximab biosimilar (Remsima) in Crohn’s disease patients in clinical practice: results after 6-months treatment [ECCO Abstract P452. Presented at: 11th Congress of ECCO, March 19–19, 2016, Amsterdam, Netherlands.
43.
Guerra Veloz MF, Belvis Jimenez M, Vazquez Moron JM, et al. Switching reference infliximab to CT-P13 in patients with inflammatory bowel disease: Multicentre study at 12 months results [ECCO Abstract P519]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
44.
Guidi L, Fiorino G, Variola A, et al. The PROSIT cohort of infliximab biosimilar in IBD: A prolonged follow-up on the efficacy and safety across Italy [ECCO Abstract OP005]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
45.
Hamanaka S, Nakagawa T, Koseki H, et al. Infliximab biosimilar in the treatment of inflammatory bowel disease: a Japanese single-cohort observational study [ECCO Abstract P329]. Presented at: 11th Congress of ECCO, March 16–19, 2016, Amsterdam, Netherlands.
46.
Hlavaty T, Krajcovicova A, Sturdik J, et al. Biosimilar infliximab CT-P13 treatment in patients with inflammatory bowel diseases: a 1-year, single-centre retrospective study [ECCO Abstract P655]. Presented at: 11th Congress of ECCO, March 16–19, 2016, Amsterdam, Netherlands.
47.
Hoivic ML, Buer LC, Bolstad N, et al. Switching from originator to biosimilar infliximab—real-world data from 18 months prospective follow-up of a single-centre IBD population [ECCO Abstract P705]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
48.
Huoponen S, Eberl A, Rasanen P, et al. Switching from originator-infliximab to biosimilar infliximab has no influence on health-related quality of life and clinical disease activity among patients with inflammatory bowel disease [ECCO Abstract P685]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
49.
Ilias A, Szanto K, Gonczi L, et al. Non-medical mandatory reversed and back and forth switch between infliximab and its biosimilar: Early clinical outcomes [ECCO Abstract P694]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
50.
Kierkus J. Preliminary assessment of efficacy and safety of switching between originator and biosimilar infliximab in paediatric Crohn Disease patients. [DDW Abstract Tu1081]. Presented at: Digestive Disease Week Annual Meeting, May 17–19, 2015, Washington, DC.
51.
Nugent S ea. EirSwitch echoes of NorSwitch: Switching biosimilar therapy in an IBD cohort an Irish experience [ECCO Abstract P430]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
52.
Petitdidier N, Gagniere C, Rentien AL, et al. Patients’ perspectives on switching from reference infliximab to CT-P13 biosimilar in patients with inflammatory bowel disease: a 12-month prospective observational cohort study [ECCO Abstract P528]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
53.
Pierik MJ, van der Meulen-de Jong AE, Bloemstaat-Minekus JPJ, et al. Switching from the originator infliximab to biosimilar CT-P13 did not change the quality of life and clinical efficacy for IBD patients in stable remission in daily clinical practice (interim analysis) [ECCO Abstract P464]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna Austria.
54.
Rodriguez Glez GE, Diaz Hernandez L, Morales Barrios JA, et al. Efficacy, safety and economic impact of the switch to biosimilar of infliximab in inflammatory bowel disease patients in clinical practice: results of one year [ECCO Abstract P629]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
55.
Sieczkowska J, Jarzebicka D, Oracz G, et al. Immunogenicity after switching from reference infliximab to biosimilar in children with Crohn’s [ECCO Abstract P617]. Presented at: 11th Congress of ECCO, March 19–19, 2016, Amsterdam, Netherlands.
56.
Sladek M, Vultaggio A, Ghione S, et al. Comparable clinical efficacy, safety and immunogenicity of infliximab biosimilar (CT-P13) after transition from reference infliximab (Remicade®) in children with established inflammatory bowel disease: a multi-centre prospective observational [ECCO Abstract P661]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain.
57.
Smits LJ, Derikx L, van Esch AA, et al. Drug survival and immunogenicity after switching from Remicade® to biosimilar CT-P13 in inflammatory bowel disease patients: two-year follow-up of a prospective observational cohort study [ECCO Abstract P490]. Presented at: 13th Congress of ECCO, February 14–17, 2018, Vienna, Austria.
58.
Suk JY, Park DI, Kim YH, et al. Efficacy and safety of infliximab’s biosimilar (REMSIMA) for IBD [ECCO abstract P540]. Presented at: 10th Congress of ECCO, February 18–21, 2015; Barcelona, Spain.
59.
Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilar: a systematic literature review of clinical outcomes. Drugs. 2018;78:463–478.CrossRef
60.
Gisbert JP, Chaparro M. Switching from and originator anti-TNF to a biosimiar in patients with inflammatory bowel disease: can it be recommended? A systematic review. Gastroenterol Hepatol. 2018;41:389–409.CrossRef
61.
Faegan BG, Lam G, Ma C, Lichtenstein GR. Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab. Aliment Pharmacol Ther. 2019;49:31–40.CrossRef
62.
Komaki Y, Yamada A, Komaki F, Micic D, Ido A, Sakuraba A. Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent (infliximab), in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;45:1043–1057.CrossRef
63.
Radin M, Sciascia S, Roccatello D, Cuadrado MJ. Infliximab biosimilars in the treatment of inflammatory bowel diseases: a systematic review. BioDrugs. 2017;31:37–49.CrossRef
64.
Faccin F, Tebbey P, Alexander E, Wang X, Cui L, Albuquerque T. The design of clinical trials to support the switching and alternation of biosimilars. Expert Opin Biol Ther. 2016;16:1445–1453.CrossRef
65.
Ben-Horin S, Yavzori M, Benhar I, et al. Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima. Gut. 2016;65:1132–1138.CrossRef
66.
Humira Product Monograph. North Chicago: Abbvie Corporation; 2017.
67.
Simponi Product Monograph. Beerse: Janssen Inc.; 2014.
68.
Cimzia Product Monograph. Oakville: UCB Canada Inc.; 2014.
69.
Enbrel Product Monograph. Mississauga: Amgen Canada Inc.; 2015.
70.
Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use. European Medicines Agency; May 2012.
71.
Scott BJ, Klein AV, Wang J. Biosimilar monoclonal antibodies: A Canadian regulatory perspective on the assessment of clinically relevant differences and indication extrapolation. J Clin Pharmacol. 2015;55:S123–S132.CrossRef
72.
Mould DR. The pharmacokinetics of biologics: a primer. Dig Dis. 2015;33:61–69.CrossRef
73.
Ben-Horin S, Vande Casteele N, Schreiber S, Lakatos PL. Biosimilars in Inflammatory bowel disease: facts and fears of extrapolation. Clin Gastroenterol Hepatol. 2016;14:1685–1696.CrossRef
74.
Gonczi L, Vegh Z, Golovics PA, et al. Prediction of short- and medium-term efficacy of biosimilar infliximab therapy Do trough levels and antidrug antibody levels or clinical and biochemical markers play the more important role? J Crohns Colitis. 2017;11:697–705.CrossRef
75.
Gecse KB, Vegh Z, Kurti Z, et al. Final results on efficacy and safety of biosimilar infliximab after one-year: results from a prospective nationwide cohort [ECCO abstract P331]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain 2017.
76.
Lovasz BD, Kurti Z, Rutka M, et al. Final results on immunogenicity profile and predictors of ADA development of biosimilar infliximab during the first 12 months of the therapy: results from a prospective nationwide cohort [ECCO abstract P592]. Presented at: 12th Congress of ECCO, February 15–18, 2017, Barcelona, Spain 2017.
77.
Metadata
Title
Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease
Authors
Edmond-Jean Bernard
Richard N. Fedorak
Vipul Jairath
Publication date
01-08-2020
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 8/2020
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-06036-0

Other articles of this Issue 8/2020

Digestive Diseases and Sciences 8/2020 Go to the issue

Original Article

Impact of Endoscopists’ Personality Traits on Adenoma and Polyp Detection Rates in Colonoscopy: A KASID Multicenter Study

Original Article

Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma

DDS AUTHOR PROFILES

Author Spotlight: Malorie Simons

Editorial

Is Tissue Really the Issue? How the Polyp Detection Rate May Be a Good Enough Quality Measure Among Trainees

FELLOWS AND YOUNG GIS SECTION

Outrunning Burnout in a GI Fellowship Program During the COVID-19 Pandemic

Editorial

Infliximab Versus Biosimilars for IBD: Is It Better to Fight Than Switch?
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits