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Published in: Advances in Therapy 6/2018

Open Access 01-06-2018 | Commentary

To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars

Authors: Mourad F. Rezk, Burkhard Pieper

Published in: Advances in Therapy | Issue 6/2018

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Abstract

Abstract

In addition to the general clinical benefit offered, biosimilars may not only generate savings for healthcare budgets but also improve patient access to biologic products. Since the first biosimilar was approved in Europe in 2006, a further 36 different biosimilar drugs have been approved for several indications. Despite the wealth of experience gained and the reported data supporting the use of biosimilars, both in naïve and biologic-experienced patients, some healthcare professionals continue to express doubt regarding the rigorous approval process for biosimilars and uncertainty with how to incorporate them into daily clinical practice. These opinions can be transferred to patients through poor or lack of communication, meaning that patients may lack confidence in treatment quality and, as a result, be susceptible to the nocebo effect. At the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals annual meeting, during a debate the question was asked as to whether the nocebo effect was in fact being used to describe “any result you don’t agree with”. Here, we detail that the nocebo effect has been demonstrated in a number of clinical trials, and that this effect may negatively affect acceptance in patients switching from an originator product to a biosimilar. Awareness of the potential for the nocebo effect and adoption of enhanced communication techniques may be useful in mitigating the nocebo effect. Effective healthcare professional–patient dialogue is key in transferring confidence to the patient, and has been shown to reduce nocebo effects in patients when switching from an originator to a biosimilar.

Funding

Biogen International GmbH.
Literature
1.
go back to reference Hauser W, Hansen E, Enck P. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch Arztebl Int. 2012;109:459–65.PubMedPubMedCentral Hauser W, Hansen E, Enck P. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch Arztebl Int. 2012;109:459–65.PubMedPubMedCentral
3.
go back to reference Faase K, Petrie K. The nocebo effect: patient expectations and medication side effects. Postgrad Med J. 2013;89:540–6.CrossRef Faase K, Petrie K. The nocebo effect: patient expectations and medication side effects. Postgrad Med J. 2013;89:540–6.CrossRef
6.
go back to reference Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389:2473–81.CrossRefPubMed Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389:2473–81.CrossRefPubMed
8.
go back to reference Yoo DH, Hrycaj P, Miranda P, 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;72:1613–20.CrossRefPubMedPubMedCentral Yoo DH, Hrycaj P, Miranda P, 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;72:1613–20.CrossRefPubMedPubMedCentral
9.
go back to reference Yoo DH, Racewicz A, Brzezicki J, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther. 2016;18:82.CrossRefPubMedPubMedCentral Yoo DH, Racewicz A, Brzezicki J, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther. 2016;18:82.CrossRefPubMedPubMedCentral
10.
go back to reference Emery P, Vencovsky J, Sylwestrzak A, et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017;76:51–7.CrossRefPubMed Emery P, Vencovsky J, Sylwestrzak A, et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2017;76:51–7.CrossRefPubMed
11.
go back to reference Park W, Yoo DH, Miranda P, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis. 2017;76:346–54.CrossRefPubMed Park W, Yoo DH, Miranda P, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis. 2017;76:346–54.CrossRefPubMed
12.
go back to reference Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2017;76:355–63.CrossRefPubMed Yoo DH, Prodanovic N, Jaworski J, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2017;76:355–63.CrossRefPubMed
13.
go back to reference Griffiths CEM, Thaci D, Gerdes S, et al. The EGALITY study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol. 2017;176:928–38.CrossRefPubMed Griffiths CEM, Thaci D, Gerdes S, et al. The EGALITY study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol. 2017;176:928–38.CrossRefPubMed
14.
go back to reference 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;389:2304–16.CrossRefPubMed 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;389:2304–16.CrossRefPubMed
15.
go back to reference Smolen JS, Choe J-Y, Prodanovic N, et al. Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann Rhuem Dis. 2018;77:234–40.CrossRef Smolen JS, Choe J-Y, Prodanovic N, et al. Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann Rhuem Dis. 2018;77:234–40.CrossRef
16.
go back to reference Boone NW, Liu L, Romberg-Camps MJ, et al. The nocebo effect challenges the non-medical infliximab switch in practice. Eur J Clin Pharmacol. 2018;74:655–61.CrossRefPubMedPubMedCentral Boone NW, Liu L, Romberg-Camps MJ, et al. The nocebo effect challenges the non-medical infliximab switch in practice. Eur J Clin Pharmacol. 2018;74:655–61.CrossRefPubMedPubMedCentral
17.
go back to reference 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;15:1677–83.CrossRefPubMed 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;15:1677–83.CrossRefPubMed
18.
go back to reference Edwards C. Switching patients from originator to biosimilar medications in rheumatoid arthritis: limiting the ‘nocebo’ effect. EMJ Rheumatol. 2017;4:42–8. Edwards C. Switching patients from originator to biosimilar medications in rheumatoid arthritis: limiting the ‘nocebo’ effect. EMJ Rheumatol. 2017;4:42–8.
19.
go back to reference Glintborg B, Omerovic E, Danebod K et al. One-year clinical outcomes in 1623 patients with inflammatory arthritis who switched from originator to biosimilar etanercept—an observational study from the danish danbio registry. Arthritis Rheumatol. 2017;69(suppl 10):Abstract 1550. Glintborg B, Omerovic E, Danebod K et al. One-year clinical outcomes in 1623 patients with inflammatory arthritis who switched from originator to biosimilar etanercept—an observational study from the danish danbio registry. Arthritis Rheumatol. 2017;69(suppl 10):Abstract 1550.
20.
go back to reference Holroyd C, Wallis D, Bennett S, et al. AB0377 switching from bio-original etanercept to biosimilar etanercept SB4: patient acceptability and outcomes in the real world. Ann Rheum Dis. 2017;76(Suppl 2):1180. Holroyd C, Wallis D, Bennett S, et al. AB0377 switching from bio-original etanercept to biosimilar etanercept SB4: patient acceptability and outcomes in the real world. Ann Rheum Dis. 2017;76(Suppl 2):1180.
21.
go back to reference Rabbitts R, Jewell T, Marrow K-L, et al. Switching to biosimilars: an early clinical review. Rheumatology. 2017;56(Suppl 2):132. Rabbitts R, Jewell T, Marrow K-L, et al. Switching to biosimilars: an early clinical review. Rheumatology. 2017;56(Suppl 2):132.
22.
go back to reference Sigurdartorri V, Husmark T, Svard A. Switching from reference product etanercept to the biosimilar SB4 in a real-life setting: follow-up of 147 patients. Ann Rheum Dis. 2017;76(Suppl 2):835. Sigurdartorri V, Husmark T, Svard A. Switching from reference product etanercept to the biosimilar SB4 in a real-life setting: follow-up of 147 patients. Ann Rheum Dis. 2017;76(Suppl 2):835.
23.
go back to reference Tweehuysen L, Huiskes V, Bemt BVD, et al. FR10200 higher acceptance and persistence rates after biosimilar transitioning in patients with a rheumatic disease after employing an enhanced communication strategy. Ann Rheum Dis. 2017;76(Suppl 2):557. Tweehuysen L, Huiskes V, Bemt BVD, et al. FR10200 higher acceptance and persistence rates after biosimilar transitioning in patients with a rheumatic disease after employing an enhanced communication strategy. Ann Rheum Dis. 2017;76(Suppl 2):557.
24.
go back to reference Glintborg B, Sorensen IJ, Loft AG, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis. 2017;76:1426–31.CrossRefPubMed Glintborg B, Sorensen IJ, Loft AG, et al. A nationwide non-medical switch from originator infliximab to biosimilar CT-P13 in 802 patients with inflammatory arthritis: 1-year clinical outcomes from the DANBIO registry. Ann Rheum Dis. 2017;76:1426–31.CrossRefPubMed
25.
go back to reference Tweehuysen L, van den Bemt BJF, van Ingen IL, et al. Subjective complaints as the main reason for biosimilar discontinuation after open-label transition from reference infliximab to biosimilar infliximab. Arthritis Rheumatol. 2018;70:60–8.CrossRefPubMed Tweehuysen L, van den Bemt BJF, van Ingen IL, et al. Subjective complaints as the main reason for biosimilar discontinuation after open-label transition from reference infliximab to biosimilar infliximab. Arthritis Rheumatol. 2018;70:60–8.CrossRefPubMed
26.
go back to reference Smolen JS, Nash P, Durez P, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918–29.CrossRefPubMed Smolen JS, Nash P, Durez P, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013;381:918–29.CrossRefPubMed
Metadata
Title
To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars
Authors
Mourad F. Rezk
Burkhard Pieper
Publication date
01-06-2018
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 6/2018
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-018-0719-8

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