Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations

Wallace J. Brownlee; Christian Wolf; Hans-Peter Hartung; Theo Dingermann; Nadia Anshasi; Richard A. C. Clark; Maria Trojano; Krzysztof Selmaj; Bernard M. J. Uitdehaag; Carmen Tur; Jens Wuerfel; Gabriele Dallmann; Julian Witte; Martina Sintzel; Olga Bobrovnikova; Jeffrey A. Cohen

doi:10.1177/13524585221116269

Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations

Wallace J. Brownlee^*, Christian Wolf, Hans-Peter Hartung, Theo Dingermann, Nadia Anshasi, Richard A. C. Clark, Maria Trojano, Krzysztof Selmaj, Bernard M. J. Uitdehaag, Carmen Tur, Jens Wuerfel, Gabriele Dallmann, Julian Witte, Martina Sintzel, Olga Bobrovnikova, Jeffrey A. Cohen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: As patents for multiple sclerosis (MS) therapies expire, follow-on disease-modifying treatments (FO-DMTs) become available at reduced cost. Concerns exist that cheaper FO-DMTs are used simply to reduce healthcare costs. However, the well-being of people with MS should take priority. Objectives: To identify best practices for FO-DMT development and use by agreeing on principles and consensus statements through appraisal of published evidence. Methods: Following a systematic review, we formulated five overarching principles and 13 consensus statements. Principles and statements were voted on by a multidisciplinary panel from 17 European countries, Argentina, Canada and the United States. Results: All principles and statements were endorsed by >80% of panellists. In brief, FO-DMTs approved within highly regulated areas can be considered effective and safe as their reference products; FO-DMTs can be evaluated case by case and do not always require Phase III trials; long-term pharmacovigilance and transparency are needed; there is lack of evidence for multiple- and cross-switching among FO-DMTs; and education is needed to address remaining concerns. Conclusion: Published data support the use of FO-DMTs in MS. The consensus may aid shared decision-making. While our consensus focused on Europe, the results may contribute to enhanced quality standards for FO-DMTs use elsewhere.

Original language	English
Pages (from-to)	2177-2189
Number of pages	13
Journal	Multiple Sclerosis Journal
Volume	28
Issue number	14
Early online date	2022
DOIs	https://doi.org/10.1177/13524585221116269
Publication status	Published - Dec 2022

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10.1177/13524585221116269

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Brownlee, W. J., Wolf, C., Hartung, H-P., Dingermann, T., Anshasi, N., Clark, R. A. C., Trojano, M., Selmaj, K., Uitdehaag, B. M. J., Tur, C., Wuerfel, J., Dallmann, G., Witte, J., Sintzel, M., Bobrovnikova, O., & Cohen, J. A. (2022). Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations. Multiple Sclerosis Journal, 28(14), 2177-2189. https://doi.org/10.1177/13524585221116269

@article{a3e9ad8df66946bfb16a8b82934d791a,

title = "Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations",

abstract = "Background: As patents for multiple sclerosis (MS) therapies expire, follow-on disease-modifying treatments (FO-DMTs) become available at reduced cost. Concerns exist that cheaper FO-DMTs are used simply to reduce healthcare costs. However, the well-being of people with MS should take priority. Objectives: To identify best practices for FO-DMT development and use by agreeing on principles and consensus statements through appraisal of published evidence. Methods: Following a systematic review, we formulated five overarching principles and 13 consensus statements. Principles and statements were voted on by a multidisciplinary panel from 17 European countries, Argentina, Canada and the United States. Results: All principles and statements were endorsed by >80% of panellists. In brief, FO-DMTs approved within highly regulated areas can be considered effective and safe as their reference products; FO-DMTs can be evaluated case by case and do not always require Phase III trials; long-term pharmacovigilance and transparency are needed; there is lack of evidence for multiple- and cross-switching among FO-DMTs; and education is needed to address remaining concerns. Conclusion: Published data support the use of FO-DMTs in MS. The consensus may aid shared decision-making. While our consensus focused on Europe, the results may contribute to enhanced quality standards for FO-DMTs use elsewhere.",

keywords = "Biosimilar, consensus, disease-modifying treatments, expert opinion, guidelines, interchangeability, multiple sclerosis, non-biological complex drugs, switching",

author = "Brownlee, {Wallace J.} and Christian Wolf and Hans-Peter Hartung and Theo Dingermann and Nadia Anshasi and Clark, {Richard A. C.} and Maria Trojano and Krzysztof Selmaj and Uitdehaag, {Bernard M. J.} and Carmen Tur and Jens Wuerfel and Gabriele Dallmann and Julian Witte and Martina Sintzel and Olga Bobrovnikova and Cohen, {Jeffrey A.}",

note = "Funding Information: The authors express their gratitude to Pieter van Galen (Brain Star, Overijse, Belgium) for administering the grants and his contribution as a past member of the Steering Committee, to Josh Lilly (Aspire Scientific, Bollington, UK) for conceptualising the systematic literature review and coordinating the initial Delphi process, as well as to Patrick Vermersch (Lille, France), Maria Pia Sormani (Genova, Italy), Xavier Montalban (Barcelona, Spain) and Volker Limmroth (K{\"o}ln, Germany) for their contributions as past members of the Steering Committee. The consensus process was seconded by the European Multiple Sclerosis Platform (EMSP; Brussels, Belgium), a pan-European patient advocacy network. The EMSP was represented in the Steering Committee by two PwMS. The author(s) disclose receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by unrestricted educational grants from Viatris, Synthon and GL Pharma. Initiative was originally taken by one of the grant givers (Mylan, now Viatris), who approached the participants of the first meeting (see Online Supplementary Table S2). Viatris also approached the companies Synthon and GL Pharma to join as grant givers. Subsequently, the project developed independently from the funders. Specifically, the funding companies had no influence on the nomination of further committee or panel members, on the selection of the final medical writing vendor, on the recommendations developed by the participants, on the voting process or the content of the manuscript nor did the funding companies review the manuscript before submission for publication. The steering committee asked Brain Star, Overijse, Belgium, to administer the grants and contracts. Infrastructure support (file repository, video conferencing and polling) was provided by Lycalis, Brussels, Belgium. The grants were used to pay honoraria for meeting participation and travel expenses for members of the steering committee and the voting panel, purchase of medical writing and coordination services, purchase and translation of literature, and payment of the open-access fees. Funding Information: The author(s) disclose receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by unrestricted educational grants from Viatris, Synthon and GL Pharma. Initiative was originally taken by one of the grant givers (Mylan, now Viatris), who approached the participants of the first meeting (see Online Supplementary Table S2 ). Viatris also approached the companies Synthon and GL Pharma to join as grant givers. Subsequently, the project developed independently from the funders. Specifically, the funding companies had no influence on the nomination of further committee or panel members, on the selection of the final medical writing vendor, on the recommendations developed by the participants, on the voting process or the content of the manuscript nor did the funding companies review the manuscript before submission for publication. The steering committee asked Brain Star, Overijse, Belgium, to administer the grants and contracts. Infrastructure support (file repository, video conferencing and polling) was provided by Lycalis, Brussels, Belgium. The grants were used to pay honoraria for meeting participation and travel expenses for members of the steering committee and the voting panel, purchase of medical writing and coordination services, purchase and translation of literature, and payment of the open-access fees. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Wallace Brownlee has received honoraria from Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Viatris. Christian Wolf is a partner at Lycalis sprl. His organisation has received compensation for consulting and speaking from Viatris, Merck KGaA, Roche, Immunic, BMS Celgene, Novartis, Teva, Synthon and Desitin. Hans-Peter Hartung has received fees for serving on steering and data-monitoring committees and lecturing from Alexion, Bayer Healthcare, Biogen, BMS Celgene, GeNeuro, Merck, Novartis, Octapharma, Roche, TG Therapeutics and UCB. Theo Dingermann has received honoraria from Hexal/Sandoz and Viatris. Nadia Anshasi: none declared. Richard A. C. Clark has received project funding for medical writing services associated with this manuscript. Maria Trojano has served on scientific advisory boards for Biogen, Novartis, Roche, Merck, BMS and Genzyme; has received speaker honoraria from Biogen, Roche, Sanofi, Merck, Genzyme and Novartis; and has received research grants from Biogen, Merck, Novartis and Roche. Krzysztof Selmaj has received honoraria for work on advisory boards and speaking for Biogen, Novartis, Roche, Celgene BMS, Merck and TG Therapeutics. Bernard M. J. Uitdehaag has received research support and/or consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva and Immunic Therapeutics. Carmen Tur is currently being funded by a Junior Leader La Caixa Fellowship (La Caixa Foundation, fellowship code: LCF/BQ/PI20/11760008). She has also received the 2021 Merck{\textquoteright}s Award for the Investigation in Multiple Sclerosis (Fundaci{\'o}n Merck Salud, Spain) and a PI21 award (Proyecto de Investigaci{\'o}n 2021) by the Spanish Ministry of Science and Innovation. She has also received funding from the UK MS Society (grant number 77) and speaker honoraria from Roche and Novartis. Jens Wuerfel is an employee of MIAC AG, Switzerland, and has received grants from the EU (Horizon 2020), the Swiss National Science Foundation, the Boehringer Ingelheim Foundation, the Novartis Foundation, the German Federal Ministries of Education and Research (BMBF) and Economic Affairs and Energy (BMWI); he has served on advisory boards for Actelion, Apellis, Bayer, Biogen, Celgene, Genzyme-Sanofi, Idorsia, InmuneBio, Novartis, Roche and TEVA. Gabriele Dallmann: none declared. Julian Witte: none declared. Martina Sintzel is partner of mcs.medical communication services, a division of 2B invincible AG. Her organisation has received funding for coordination and medical writing services associated with this project. Furthermore, her organisation received compensation for consulting from Bayer and Fresenius Kabi as well as numerous organisations outside of the healthcare industry. Olga Bobrovnikova: none declared. Jeffrey A. Cohen has received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis and PSI; speaking for H3 Communications; and serving as an Editor of Multiple Sclerosis Journal. Publisher Copyright: {\textcopyright} The Author(s), 2022.",

year = "2022",

month = dec,

doi = "10.1177/13524585221116269",

language = "English",

volume = "28",

pages = "2177--2189",

journal = "Multiple Sclerosis",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

number = "14",

}

Brownlee, WJ, Wolf, C, Hartung, H-P, Dingermann, T, Anshasi, N, Clark, RAC, Trojano, M, Selmaj, K, Uitdehaag, BMJ, Tur, C, Wuerfel, J, Dallmann, G, Witte, J, Sintzel, M, Bobrovnikova, O & Cohen, JA 2022, 'Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations', Multiple Sclerosis Journal, vol. 28, no. 14, pp. 2177-2189. https://doi.org/10.1177/13524585221116269

TY - JOUR

T1 - Use of follow-on disease-modifying treatments for multiple sclerosis

T2 - Consensus recommendations

AU - Brownlee, Wallace J.

AU - Wolf, Christian

AU - Hartung, Hans-Peter

AU - Dingermann, Theo

AU - Anshasi, Nadia

AU - Clark, Richard A. C.

AU - Trojano, Maria

AU - Selmaj, Krzysztof

AU - Uitdehaag, Bernard M. J.

AU - Tur, Carmen

AU - Wuerfel, Jens

AU - Dallmann, Gabriele

AU - Witte, Julian

AU - Sintzel, Martina

AU - Bobrovnikova, Olga

AU - Cohen, Jeffrey A.

N1 - Funding Information: The authors express their gratitude to Pieter van Galen (Brain Star, Overijse, Belgium) for administering the grants and his contribution as a past member of the Steering Committee, to Josh Lilly (Aspire Scientific, Bollington, UK) for conceptualising the systematic literature review and coordinating the initial Delphi process, as well as to Patrick Vermersch (Lille, France), Maria Pia Sormani (Genova, Italy), Xavier Montalban (Barcelona, Spain) and Volker Limmroth (Köln, Germany) for their contributions as past members of the Steering Committee. The consensus process was seconded by the European Multiple Sclerosis Platform (EMSP; Brussels, Belgium), a pan-European patient advocacy network. The EMSP was represented in the Steering Committee by two PwMS. The author(s) disclose receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by unrestricted educational grants from Viatris, Synthon and GL Pharma. Initiative was originally taken by one of the grant givers (Mylan, now Viatris), who approached the participants of the first meeting (see Online Supplementary Table S2). Viatris also approached the companies Synthon and GL Pharma to join as grant givers. Subsequently, the project developed independently from the funders. Specifically, the funding companies had no influence on the nomination of further committee or panel members, on the selection of the final medical writing vendor, on the recommendations developed by the participants, on the voting process or the content of the manuscript nor did the funding companies review the manuscript before submission for publication. The steering committee asked Brain Star, Overijse, Belgium, to administer the grants and contracts. Infrastructure support (file repository, video conferencing and polling) was provided by Lycalis, Brussels, Belgium. The grants were used to pay honoraria for meeting participation and travel expenses for members of the steering committee and the voting panel, purchase of medical writing and coordination services, purchase and translation of literature, and payment of the open-access fees. Funding Information: The author(s) disclose receipt of the following financial support for the research, authorship and/or publication of this article: This study was funded by unrestricted educational grants from Viatris, Synthon and GL Pharma. Initiative was originally taken by one of the grant givers (Mylan, now Viatris), who approached the participants of the first meeting (see Online Supplementary Table S2 ). Viatris also approached the companies Synthon and GL Pharma to join as grant givers. Subsequently, the project developed independently from the funders. Specifically, the funding companies had no influence on the nomination of further committee or panel members, on the selection of the final medical writing vendor, on the recommendations developed by the participants, on the voting process or the content of the manuscript nor did the funding companies review the manuscript before submission for publication. The steering committee asked Brain Star, Overijse, Belgium, to administer the grants and contracts. Infrastructure support (file repository, video conferencing and polling) was provided by Lycalis, Brussels, Belgium. The grants were used to pay honoraria for meeting participation and travel expenses for members of the steering committee and the voting panel, purchase of medical writing and coordination services, purchase and translation of literature, and payment of the open-access fees. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Wallace Brownlee has received honoraria from Biogen, Celgene, Merck, Novartis, Roche, Sanofi and Viatris. Christian Wolf is a partner at Lycalis sprl. His organisation has received compensation for consulting and speaking from Viatris, Merck KGaA, Roche, Immunic, BMS Celgene, Novartis, Teva, Synthon and Desitin. Hans-Peter Hartung has received fees for serving on steering and data-monitoring committees and lecturing from Alexion, Bayer Healthcare, Biogen, BMS Celgene, GeNeuro, Merck, Novartis, Octapharma, Roche, TG Therapeutics and UCB. Theo Dingermann has received honoraria from Hexal/Sandoz and Viatris. Nadia Anshasi: none declared. Richard A. C. Clark has received project funding for medical writing services associated with this manuscript. Maria Trojano has served on scientific advisory boards for Biogen, Novartis, Roche, Merck, BMS and Genzyme; has received speaker honoraria from Biogen, Roche, Sanofi, Merck, Genzyme and Novartis; and has received research grants from Biogen, Merck, Novartis and Roche. Krzysztof Selmaj has received honoraria for work on advisory boards and speaking for Biogen, Novartis, Roche, Celgene BMS, Merck and TG Therapeutics. Bernard M. J. Uitdehaag has received research support and/or consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva and Immunic Therapeutics. Carmen Tur is currently being funded by a Junior Leader La Caixa Fellowship (La Caixa Foundation, fellowship code: LCF/BQ/PI20/11760008). She has also received the 2021 Merck’s Award for the Investigation in Multiple Sclerosis (Fundación Merck Salud, Spain) and a PI21 award (Proyecto de Investigación 2021) by the Spanish Ministry of Science and Innovation. She has also received funding from the UK MS Society (grant number 77) and speaker honoraria from Roche and Novartis. Jens Wuerfel is an employee of MIAC AG, Switzerland, and has received grants from the EU (Horizon 2020), the Swiss National Science Foundation, the Boehringer Ingelheim Foundation, the Novartis Foundation, the German Federal Ministries of Education and Research (BMBF) and Economic Affairs and Energy (BMWI); he has served on advisory boards for Actelion, Apellis, Bayer, Biogen, Celgene, Genzyme-Sanofi, Idorsia, InmuneBio, Novartis, Roche and TEVA. Gabriele Dallmann: none declared. Julian Witte: none declared. Martina Sintzel is partner of mcs.medical communication services, a division of 2B invincible AG. Her organisation has received funding for coordination and medical writing services associated with this project. Furthermore, her organisation received compensation for consulting from Bayer and Fresenius Kabi as well as numerous organisations outside of the healthcare industry. Olga Bobrovnikova: none declared. Jeffrey A. Cohen has received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis and PSI; speaking for H3 Communications; and serving as an Editor of Multiple Sclerosis Journal. Publisher Copyright: © The Author(s), 2022.

PY - 2022/12

Y1 - 2022/12

N2 - Background: As patents for multiple sclerosis (MS) therapies expire, follow-on disease-modifying treatments (FO-DMTs) become available at reduced cost. Concerns exist that cheaper FO-DMTs are used simply to reduce healthcare costs. However, the well-being of people with MS should take priority. Objectives: To identify best practices for FO-DMT development and use by agreeing on principles and consensus statements through appraisal of published evidence. Methods: Following a systematic review, we formulated five overarching principles and 13 consensus statements. Principles and statements were voted on by a multidisciplinary panel from 17 European countries, Argentina, Canada and the United States. Results: All principles and statements were endorsed by >80% of panellists. In brief, FO-DMTs approved within highly regulated areas can be considered effective and safe as their reference products; FO-DMTs can be evaluated case by case and do not always require Phase III trials; long-term pharmacovigilance and transparency are needed; there is lack of evidence for multiple- and cross-switching among FO-DMTs; and education is needed to address remaining concerns. Conclusion: Published data support the use of FO-DMTs in MS. The consensus may aid shared decision-making. While our consensus focused on Europe, the results may contribute to enhanced quality standards for FO-DMTs use elsewhere.

AB - Background: As patents for multiple sclerosis (MS) therapies expire, follow-on disease-modifying treatments (FO-DMTs) become available at reduced cost. Concerns exist that cheaper FO-DMTs are used simply to reduce healthcare costs. However, the well-being of people with MS should take priority. Objectives: To identify best practices for FO-DMT development and use by agreeing on principles and consensus statements through appraisal of published evidence. Methods: Following a systematic review, we formulated five overarching principles and 13 consensus statements. Principles and statements were voted on by a multidisciplinary panel from 17 European countries, Argentina, Canada and the United States. Results: All principles and statements were endorsed by >80% of panellists. In brief, FO-DMTs approved within highly regulated areas can be considered effective and safe as their reference products; FO-DMTs can be evaluated case by case and do not always require Phase III trials; long-term pharmacovigilance and transparency are needed; there is lack of evidence for multiple- and cross-switching among FO-DMTs; and education is needed to address remaining concerns. Conclusion: Published data support the use of FO-DMTs in MS. The consensus may aid shared decision-making. While our consensus focused on Europe, the results may contribute to enhanced quality standards for FO-DMTs use elsewhere.

KW - Biosimilar

KW - consensus

KW - disease-modifying treatments

KW - expert opinion

KW - guidelines

KW - interchangeability

KW - multiple sclerosis

KW - non-biological complex drugs

KW - switching

UR - http://www.scopus.com/inward/record.url?scp=85137248355&partnerID=8YFLogxK

U2 - 10.1177/13524585221116269

DO - 10.1177/13524585221116269

M3 - Article

C2 - 36000489

SN - 1352-4585

VL - 28

SP - 2177

EP - 2189

JO - Multiple Sclerosis

JF - Multiple Sclerosis

IS - 14

ER -

Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations

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