References

This page contains detailed information about relevant biosimilar studies. Click the links below to explore each section.

Infliximab Adult Biosimilar Studies

Ye BD, Pesegova M, Alexeeva O, et al. Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease: an international, randomized, double-blind, phase 3 non-inferiority study. Lancet. 2019;393:1699–1707.

  • Randomized, multicenter, double-blind, phase 3 non-inferiority study, including adult Crohn’s disease patients with active disease randomly assigned to receive either infliximab originator, infliximab biosimilar (CT-P13), infliximab originator than switched to infliximab biosimilar (CT-P13) at 30 weeks, or infliximab biosimilar (CT-P13) than switched to infliximab originator at 30 weeks.
  • This study found non-inferiority of infliximab biosimilar (CT-P13) to infliximab originator and similar outcomes in patients whether they switched or continued on the therapy they started on.

Meyer A, Rudant J, Drouin J, Weill A, Carbonnel F, Coste J. Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study. Ann Intern Med. 2019 Jan 15;170(2):99-107.

  • French nationwide health administrative database compared Crohn’s disease outcomes (composite end point of death, Crohn disease related surgery, hospitalization, and change of biologic therapy) amongst patients on infliximab biosimilars with originator infliximab in 5050 Crohn’s patients.
  • There were no differences in outcomes and adverse events between patients started on infliximab originator and infliximab biosimilar.

Jorgensen 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.

  • A randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Included adult patients with IBD, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and psoriasis that were stable on infliximab originator and were randomised to either continue infliximab originator or to switch to infliximab biosimilar (CT-P13).
  • Switching from the infliximab originator to the infliximab biosimilar (CT-P13) was not inferior to continued treatment. The frequency of adverse events was similar between the two groups.

Goll GL, Jørgensen KK, Sexton J, Olsen IC, Bolstad N, Haavardsholm EA, Lundin KEA, Tveit KS, Lorentzen M, Berset IP, Fevang BTS, Kalstad S, Ryggen K, Warren DJ, Klaasen RA, Asak Ø, Baigh S, Blomgren IM, Brenna Ø, Bruun TJ, Dvergsnes K, Frigstad SO, Hansen IM, Hatten ISH, Huppertz-Hauss G, Henriksen M, Hoie SS, Krogh J, Midtgard IP, Mielnik P, Moum B, Noraberg G, Poyan A, Prestegård U, Rashid HU, Strand EK, Skjetne K, Seeberg KA, Torp R, Ystrøm CM, Vold C, Zettel CC, Waksvik K, Gulbrandsen B, Hagfors J, Mørk C, Jahnsen J, Kvien TK. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J Intern Med. 2019 Jun;285(6):653-669.

  • Extension of the NOR-SWITCH trial. This study included patients that continued on the infliximab biosimilar (CT-P13) and patients treated with infliximab originator in the NOR-SWITCH trial and switched to infliximab biosimilar (CT-P13).
  • The NOR-SWITCH extension trial showed no difference in safety and efficacy between patients maintaining on the infliximab biosimilar (CT-P13) or patients that switched from infliximab originator to infliximab biosimilar (CT-P13).

Mahmmod S, Schultheiss JPD, van Bodegraven AA, Dijkstra G, Gilissen LPL, Hoentjen F, Lutgens MWMD, Mahmmod N, van der Meulen-de Jong AE, Smits LJT, Tan ACITL, Oldenburg B, Fidder HH. Outcome of Reverse Switching From CT-P13 to Originator Infliximab in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis. 2021 Nov 15;27(12):1954-1962.

  • Retrospective multicenter cohort study, of adult patients with IBD from Netherlands that had switched from infliximab originator to infliximab biosimilar (CT-P13) that developed worsening gastrointestinal symptoms, adverse effects, or loss of response after the switch and was switched back (reverse switching) to the infliximab originator.
  • Reverse switching occurred in 10% of patients and reported improvement of symptoms was seen in 73% of patients.

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Infliximab Pediatric Biosimilar Studies

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 Feb 15;24(3):607-616.

  • Prospective observation study that followed pediatric patients with IBD that continued infliximab originator or switched to infliximab biosimilar (CT-P13).
  • Switching from maintenance infliximab originator to infliximab biosimilar (CT-P13) did not result in any significant differences in efficacy, pharmacokinetics, or immunogenicity in patients with pediatric IBD.

    Dipasquale V, Romano C. Biosimilar infliximab in paediatric inflammatory bowel disease: Efficacy, immunogenicity and safety. J Clin Pharm Ther. 2020 Dec;45(6):1228-1234. doi: 10.1111/jcpt.13239.

    • Comprehensive review of pediatric IBD studies that assessed the efficacy of infliximab biosimilars.
    • Pediatric IBD patients who are infliximab naïve or have been switch to the infliximab biosimilar had similar rates of efficacy, immunogenicity, and safety regardless if treated with the infliximab originator or if switched to the infliximab biosimilar.

    Morris GA, McNicol M, Boyle B, Donegan A, Dotson J, Michel HK, Maltz RM. Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money. Inflamm Bowel Dis. 2022 Mar 30;28(4):531-538

    • Using quality improvement methodology Nationwide Children’s Hospital was able to increase utilization of infliximab biosimilars from 1% to 96% without compromising patient clinical outcomes or safety.
    • There was also a significant cost savings with increase infliximab biosimilar usage.

    van Hoeve K, Dreesen E, Hoffman I, Van Assche G, Ferrante M, Gils A, Vermeire S. Efficacy, Pharmacokinetics, and Immunogenicity is Not Affected by Switching From Infliximab Originator to a Biosimilar in Pediatric Patients With Inflammatory Bowel Disease. Ther Drug Monit. 2019 Jun;41(3):317-324.

    • A single-center, prospective study of 42 children with IBD whom were switched from infliximab originator to infliximab biosimilar (CT-P13).
    • There was no change in efficacy, pharmacokinetics, immunogenicity, or safety following the switch.

    Gervais L, McLean LL, Wilson ML, Cameron C, Curtis L, Garrick V, Armstrong K, Tayler R, Henderson P, Hansen R, Chalmers I, Wilson DC, Russell RK. Switching From Originator to Biosimilar Infliximab in Paediatric Inflammatory Bowel Disease Is Feasible and Uneventful. J Pediatr Gastroenterol Nutr. 2018 Dec;67(6):745-748.

    • Prospective observation study of 33 pediatric patients with IBD whom were switched from infliximab originator to infliximab biosimilar (CT-P13).
    • Switching was not associated with increase infusion reactions, loss of effectiveness, antidrug antibodies, tough drug levels, or adverse events.

    Maltz RM, McClinchie MG, Boyle BM, McNicol M, Morris GA, Crawford EC, Moses J, Kim SC. Biosimilars for Pediatric Patients With Inflammatory Bowel Disease: Pediatric Gastroenterology Clinical Practice Survey. J Pediatr Gastroenterol Nutr. 2023 May 1;76(5):616-621.

    • A cross-sectional survey of pediatric gastroenterology physicians from the United States evaluating their perspectives towards biosimilars.
    • Nearly 90% of pediatric gastroenterologists felt comfortable prescribing an infliximab biosimilar, and 70% felt comfortable with a one-time switch to the biosimilar if the patient was in clinical remission.
    • Involvement in ImproveCareNow a learning health system and caring for higher numbers of patients with IBD was associated with increased provider comfort with biosimilar use.

    Yossef L, Wright M, Benedict J, Morris GA, McNicol M, Boyle B, Dotson JL, Michel HK, Maltz RM. Patient and Caregivers’ Perspectives on Biosimilar Use in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2022 Jul 1;75(1):59-63.

    • A cross-sectional survey of patients with IBD on infliximab originator and caregivers of patients with IBD on infliximab originator evaluating their perspectives towards biosimilars.
    • The majority of pediatric patients and caregivers had never heard of biosimilars. Caregivers that had heard of biosimilars before the study were more likely to have a negative perception of them.
    • This study highlights the importance of providing thorough and accurate education to pediatric patients and families regarding the safety and efficacy of biosimilars.

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    Adalimumab Adult Biosimilar Studies

    Hanauer S, Liedert B, Balser S, Brockstedt E, Moschetti V, Schreiber S. Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):816-825.

    • Phase 3, randomized, double-blind study from Europe and the United States including adult patients with moderately to severely active Crohn’s disease. Patients were randomized to adalimumab originator or adalimumab biosimilar (BI 695501). At 24 weeks patients on adalimumab originator were switched to adalimumab biosimilar (BI 695501).
    • There was similar safety and efficacy outcomes amongst patients with Crohn’s disease that were started on adalimumab originator or adalimumab biosimilar (BI 695501).
    • Amongst the patients that switched from adalimumab originator to adalimumab biosimilar (BI 695501) there was no impact on clinical outcomes.

    Mocci G, Bodini G, Allegretta L, Cazzato AI, Chiri S, Aragona G, Perazzo P, Ferronato A, Graziani MG, Pagnini C, Zampaletta C, Graziosi C, Picchio M, Elisei W, Maconi G, Tursi A. Adalimumab Biosimilar GP2017 versus Adalimumab Originator in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study. Biomedicines. 2022 Jul 26;10(8):1799.

    • Multicenter, retrospective study assessed clinical outcomes amongst patients with IBD that were started on adalimumab originator or adalimumab biosimilar (GP2017).
    • There were similar efficacy and safety in patients with IBD that were started on adalimumab originator or adalimumab biosimilar (GP2017).

    Tursi A, Mocci G, Cuomo A, Ferronato A, Elisei W, Picchio M, Maconi G, Scaldaferri F, Papa A; Italian group for switch of biologics; Allegretta L, Aragona G, Bianco MA, Colucci R, Della Valle N, Faggiani R, Forti G, Gaiani F, Giorgetti G, Graziani MG, Lofano K, Lorenzetti R, Larussa T, Penna A, Bassotti G, Cazzato AI, Chiri S, Clemente V, Cocco A, De’ Angelis G, Donnarumma L, Graziosi C, Le Grazie M, Luzza F, Meucci C, Monterubbianesi R, Pagnini C, Perazzo P, Pica R, Pranzo G, Rodino’ S, Sacco R, Sebkova L, Scarcelli A, Serio M, Napolitano D, Pugliese D, Schiavoni E, Turchini L, Armuzzi A, Zampaletta C. Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy. J Gastrointestin Liver Dis. 2022 Dec 16;31(4):411-416.

    • A multicenter retrospective study comparing the efficacy and safety of four adalimumab biosimilars (SB5, APB501, GP2017, and MSB11022) in patients with IBD.
    • There was no difference in efficacy and safety between the four adalimumab biosimilars (SB5, APB501, GP2017, and MSB11022).

    Menter A, Cohen S, Kay J, Strand V, Gottlieb A, Hanauer S, Eduru SK, Buschke S, Lang B, Liesenfeld KH, Schaible J, McCabe D. Switching Between Adalimumab Reference Product and BI 695501 in Patients with Chronic Plaque Psoriasis (VOLTAIRE-X): A Randomized Controlled Trial. Am J Clin Dermatol. 2022 Sep;23(5):719-728.

    • A phase 3, double-blind, randomized controlled trial to assess whether multiple switches (interchangeable) between adalimumab originator and adalimumab biosimilar (BI 695501) lead to equivalent pharmacokinetics, safety, and efficacy in patients with moderate-to-severe chronic plaque psoriasis.
    • There was highly similar efficacy, immunogenicity, and safety in patients who received either adalimumab originator or who underwent multiple switches between adalimumab originator and adalimumab biosimilar (BI 695501).

    Tapete G, Bertani L, Pieraccini A, Lynch EN, Giannotta M, Morganti R, Biviano I, Naldini S, Mumolo MG, De Nigris F, Calella F, Bagnoli S, Minciotti M, Maltinti S, Rentini S, Ceccarelli L, Lionetti P, Milla M, Costa F. Effectiveness and Safety of Nonmedical Switch From Adalimumab Originator to SB5 Biosimilar in Patients With Inflammatory Bowel Diseases: Twelve-Month Follow-Up From the TABLET Registry. Inflamm Bowel Dis. 2022 Jan 5;28(1):62-69.

    • Prospective study that assessed efficacy and safety in adult patients with IBD that switched from adalimumab originator to adalimumab biosimilar (SB5) vs patients naïve to adalimumab and started on adalimumab biosimilar (SB5).
    • Adalimumab biosimilar (SB5) was effective and safe in the treatment of IBD, both in the naïve cohort and in the switching cohort.

    Lukas M, Kolar M, Reissigova J, Duricova D, Machkova N, Hruba V, Lukas M, Vasatko M, Jirsa J, Pudilova K, Malickova K. A switch from originator-adalimumab to the biosimilar SB5 in patients with Crohn’s disease: an analysis of two propensity score-matched cohorts. Scand J Gastroenterol. 2022 Jul;57(7):814-824.

    • Prospective, observational, propensity score matched study that assessed efficacy in adult patients with Crohn’s disease that switched from adalimumab originator to adalimumab biosimilar (SB5) vs patients on adalimumab originator.
    • There were similar efficacy amongst patients on adalimumab originator and patients that switched to the adalimumab biosimilar (SB5) at 52 and 102 weeks.

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    Nocebo Effect Studies

    Pouillon L, Danese S, Hart A, Fiorino G, Argollo M, Selmi C, Carlo-Stella C, Loeuille D, Costanzo A, Lopez A, Vegni E, Radice S, Gilardi D, Socha M, Fazio M, González-Lorenzo M, Bonovas S, Magro F, Peyrin-Biroulet L. Consensus report: clinical recommendations for the prevention and management of the nocebo effect in biosimilar-treated IBD patients. Aliment Pharmacol Ther. 2019 May;49(9):1181-1187.

    • Evidence-based consensus recommendations for the prevention and management of the nocebo effect in biosimilar-treated patients with IBD.
    • Patient-healthcare provider relationship is a key driver of acceptance of biosimilars, which limits the risk of negative bias and the nocebo effect. Lack of knowledge among patients and healthcare providers about the effectiveness and safety of biosimilars should be minimized.
    • Education about biosimilars needs to be tailored to the individual patient, and positive framing is recommended.

    Petit J, Antignac M, Poilverd RM, Baratto R, Darthout S, Desouches S, Louati K, Deparis N, Berenbaum F, Beauvais C. Multidisciplinary team intervention to reduce the nocebo effect when switching from the originator infliximab to a biosimilar. RMD Open. 2021 Jan;7(1):e001396.

    • A tailored communication with a prominent role of nurses reduced the nocebo effect in non-medical switches from the infliximab originator to infliximab biosimilar. This was achieved by  training healthcare professional on the safety and efficacy of switching to a biosimilar and having nurses disseminate the information on biosimilars with a consistent vocabulary.

    Gasteiger C, Jones ASK, Kleinstäuber M, Lobo M, Horne R, Dalbeth N, Petrie KJ. Effects of Message Framing on Patients’ Perceptions and Willingness to Change to a Biosimilar in a Hypothetical Drug Switch. Arthritis Care Res (Hoboken). 2020 Sep;72(9):1323-1330.

    • The aim of this study was to measure the effect of differently framed explanations on patients’ perceptions of and willingness to change to a biosimilar in a hypothetical drug switch.
    • Positive framing with body language and verbal cues can improve perceptions of and willingness to switch to a biosimilar in patients currently taking a biologic treatment.

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