Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Cyrus Daruwalla; Vahid Shaygannejad; Serkan Ozakbas; Eva Kubala Havrdova; Dana Horakova; Raed Alroughani; Cavit Boz; Francesco Patti; Marco Onofrj; Alessandra Lugaresi; Sara Eichau; Marc Girard; Alexandre Prat; Pierre Duquette; Bassem Yamout; Samia J Khoury; Seyed Aidin Sajedi; Recai Turkoglu; Ayse Altintas; Olga Skibina; Katherine Buzzard; Pierre Grammond; Rana Karabudak; Anneke van der Walt; Helmut Butzkueven; Davide Maimone; Jeannette Lechner-Scott; Aysun Soysal; Nevin John; Julie Prevost; Daniele Spitaleri; Cristina Ramo-Tello; Oliver Gerlach; Gerardo Iuliano; Matteo Foschi; Radek Ampapa; Vincent van Pesch; Michael Barnett; Nevin Shalaby; Marie D'hooghe; Jens Kuhle; Maria Jose Sa; Marzena Fabis-Pedrini; Allan Kermode; Saloua Mrabet; Riadh Gouider; Suzanne Hodgkinson; Guy Laureys; Liesbeth Van Hijfte; Richard Macdonell; Celia Oreja-Guevara; Edgardo Cristiano; Pamela McCombe; Jose Luis Sanchez-Menoyo; Bhim Singhal; Yolanda Blanco; Stella Hughes; Justin Garber; Claudio Solaro; Chris McGuigan; Bruce Taylor; Koen de Gans; Mario Habek; Abdullah Al-Asmi; Simu Mihaela; Tamara Castillo Triviño; Talal Al-Harbi; Juan Ignacio Rojas; Orla Gray; Dheeraj Khurana; Bart Van Wijmeersch; Nikolaos Grigoriadis; Jihad Inshasi; Jiwon Oh; Eduardo Aguera-Morales; Yara Fragoso; Fraser Moore; Cameron Shaw; Seyed Mohammad Baghbanian; Neil Shuey; Barbara Willekens; Todd A Hardy; Danny Decoo; Angel Perez Sempere; Deborah Field; Ray Wynford-Thomas; Nick G Cunniffe; Izanne Roos; Charles B Malpas; Alasdair J Coles; Tomas Kalincik; J William L Brown

doi:10.1177/13524585231151951

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Cyrus Daruwalla, Vahid Shaygannejad, Serkan Ozakbas, Eva Kubala Havrdova, Dana Horakova, Raed Alroughani, Cavit Boz, Francesco Patti, Marco Onofrj, Alessandra Lugaresi, Sara Eichau, Marc Girard, Alexandre Prat, Pierre Duquette, Bassem Yamout, Samia J Khoury, Seyed Aidin Sajedi, Recai Turkoglu, Ayse Altintas, Olga SkibinaKatherine Buzzard, Pierre Grammond, Rana Karabudak, Anneke van der Walt, Helmut Butzkueven, Davide Maimone, Jeannette Lechner-Scott, Aysun Soysal, Nevin John, Julie Prevost, Daniele Spitaleri, Cristina Ramo-Tello, Oliver Gerlach, Gerardo Iuliano, Matteo Foschi, Radek Ampapa, Vincent van Pesch, Michael Barnett, Nevin Shalaby, Marie D'hooghe, Jens Kuhle, Maria Jose Sa, Marzena Fabis-Pedrini, Allan Kermode, Saloua Mrabet, Riadh Gouider, Suzanne Hodgkinson, Guy Laureys, Liesbeth Van Hijfte, Richard Macdonell, Celia Oreja-Guevara, Edgardo Cristiano, Pamela McCombe, Jose Luis Sanchez-Menoyo, Bhim Singhal, Yolanda Blanco, Stella Hughes, Justin Garber, Claudio Solaro, Chris McGuigan, Bruce Taylor, Koen de Gans, Mario Habek, Abdullah Al-Asmi, Simu Mihaela, Tamara Castillo Triviño, Talal Al-Harbi, Juan Ignacio Rojas, Orla Gray, Dheeraj Khurana, Bart Van Wijmeersch, Nikolaos Grigoriadis, Jihad Inshasi, Jiwon Oh, Eduardo Aguera-Morales, Yara Fragoso, Fraser Moore, Cameron Shaw, Seyed Mohammad Baghbanian, Neil Shuey, Barbara Willekens, Todd A Hardy, Danny Decoo, Angel Perez Sempere, Deborah Field, Ray Wynford-Thomas, Nick G Cunniffe, Izanne Roos, Charles B Malpas, Alasdair J Coles, Tomas Kalincik, J William L Brown

Medicine

نتاج البحث: المساهمة في مجلة › Article › مراجعة النظراء

3 اقتباسات (Scopus)

ملخص

BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.

OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS.

METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.

RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically.

CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

اللغة الأصلية	English
الصفحات (من إلى)	875-883
عدد الصفحات	9
دورية	Multiple Sclerosis Journal
مستوى الصوت	29
رقم الإصدار	7
تاريخ مبكر على الإنترنت	فبراير 27 2023
المعرِّفات الرقمية للأشياء	https://doi.org/10.1177/13524585231151951 https://doi.org/10.1177/13524585231151951
حالة النشر	Published - يونيو 2023

ASJC Scopus subject areas

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قم بذكر هذا

Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Horakova, D., Alroughani, R., Boz, C., Patti, F., Onofrj, M., Lugaresi, A., Eichau, S., Girard, M., Prat, A., Duquette, P., Yamout, B., Khoury, S. J., Sajedi, S. A., Turkoglu, R., Altintas, A., ... Brown, J. W. L. (2023). Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis. Multiple Sclerosis Journal, 29(7), 875-883. https://doi.org/10.1177/13524585231151951, https://doi.org/10.1177/13524585231151951

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis. / Daruwalla, Cyrus; Shaygannejad, Vahid; Ozakbas, Serkan وآخرون.
في: Multiple Sclerosis Journal, المجلد 29, رقم 7, ٠٦.٢٠٢٣, صفحة 875-883.

نتاج البحث: المساهمة في مجلة › Article › مراجعة النظراء

Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Triviño, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T & Brown, JWL 2023, 'Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis', Multiple Sclerosis Journal, المجلد 29, رقم 7, الصفحات 875-883. https://doi.org/10.1177/13524585231151951, https://doi.org/10.1177/13524585231151951

Daruwalla C, Shaygannejad V, Ozakbas S, Havrdova EK, Horakova D, Alroughani R وآخرون. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis. Multiple Sclerosis Journal. 2023 يونيو;29(7):875-883. Epub 2023 فبراير 27. doi: 10.1177/13524585231151951, 10.1177/13524585231151951

@article{8c6c7197c06042a6b6143ee557450524,

title = "Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis",

abstract = "BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS.METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.",

keywords = "Multiple sclerosis, prognosis, Multiple Sclerosis, Recurrence, Prognosis, Humans, Multiple Sclerosis, Relapsing-Remitting/drug therapy",

author = "Cyrus Daruwalla and Vahid Shaygannejad and Serkan Ozakbas and Havrdova, {Eva Kubala} and Dana Horakova and Raed Alroughani and Cavit Boz and Francesco Patti and Marco Onofrj and Alessandra Lugaresi and Sara Eichau and Marc Girard and Alexandre Prat and Pierre Duquette and Bassem Yamout and Khoury, {Samia J} and Sajedi, {Seyed Aidin} and Recai Turkoglu and Ayse Altintas and Olga Skibina and Katherine Buzzard and Pierre Grammond and Rana Karabudak and {van der Walt}, Anneke and Helmut Butzkueven and Davide Maimone and Jeannette Lechner-Scott and Aysun Soysal and Nevin John and Julie Prevost and Daniele Spitaleri and Cristina Ramo-Tello and Oliver Gerlach and Gerardo Iuliano and Matteo Foschi and Radek Ampapa and {van Pesch}, Vincent and Michael Barnett and Nevin Shalaby and Marie D'hooghe and Jens Kuhle and Sa, {Maria Jose} and Marzena Fabis-Pedrini and Allan Kermode and Saloua Mrabet and Riadh Gouider and Suzanne Hodgkinson and Guy Laureys and {Van Hijfte}, Liesbeth and Richard Macdonell and Celia Oreja-Guevara and Edgardo Cristiano and Pamela McCombe and Sanchez-Menoyo, {Jose Luis} and Bhim Singhal and Yolanda Blanco and Stella Hughes and Justin Garber and Claudio Solaro and Chris McGuigan and Bruce Taylor and {de Gans}, Koen and Mario Habek and Abdullah Al-Asmi and Simu Mihaela and {Castillo Trivi{\~n}o}, Tamara and Talal Al-Harbi and Rojas, {Juan Ignacio} and Orla Gray and Dheeraj Khurana and {Van Wijmeersch}, Bart and Nikolaos Grigoriadis and Jihad Inshasi and Jiwon Oh and Eduardo Aguera-Morales and Yara Fragoso and Fraser Moore and Cameron Shaw and Baghbanian, {Seyed Mohammad} and Neil Shuey and Barbara Willekens and Hardy, {Todd A} and Danny Decoo and Sempere, {Angel Perez} and Deborah Field and Ray Wynford-Thomas and Cunniffe, {Nick G} and Izanne Roos and Malpas, {Charles B} and Coles, {Alasdair J} and Tomas Kalincik and Brown, {J William L}",

note = "Funding Information: A.A. received speaker honoraria from Merck, Alexion; received travel and registration grants from Merck. Funding Information: A.L. has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme and, Teva, and Bristol Myers Squibb. Her institutions have received research grants from Novartis and Sanofi/Genzyme. Funding Information: N.G. received honoraria and travel support, Consultancy fees, Lecture fees from Biogen Idec, Biologix, Novartis, TEVA, Bayer, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE, ELPEN. Research grants from Biogen Idec, Novartis, TEVA, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE Funding Information: T.C.T. received speaking/consulting fees and/or travel funding from Almirall, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Funding Information: H.B. received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers{\textquoteright} bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd and Merck; has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Funding Information: F.P. received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. He received research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association and University of Catania. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.K.H. received honoraria/research support from Biogen, Merck Serono, Novartis, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis, and Sanofi Genzyme. She was also supported by the Charles University: Cooperatio Program in neuroscience. D.H. received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck Healthcare KGaA (Darmstadt, Germany), Bayer, Sanofi, Roche, and Teva, as well as support for research activities from Biogen. She was also supported by the Charles University: Cooperatio Program in neuroscience. R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. C.B. received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. Funding Information: I.R. served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck and Biogen. Izanne Roos receives research support from Multiple Sclerosis Australia and the Trish Multiple Sclerosis Research Foundation. Funding Information: M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD . He has also received a research grant from Canadian Institutes of Health Research. Funding Information: B.W. received honoraria for acting as a member of Scientific Advisory Boards for Almirall, Biogen, Celgene/BMS, Merck Serono, Novartis, Roche, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Merck Serono, Novartis, Roche, Sanofi-Genzyme; research and/or patient support grants from Roche, Biogen, Merck-Serono, Sanofi-Genzyme; research support from FWO. Honoraria and grants were paid to UZA/UZA Foundation. Publisher Copyright: {\textcopyright} The Author(s), 2023.",

year = "2023",

month = jun,

doi = "10.1177/13524585231151951",

language = "English",

volume = "29",

pages = "875--883",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

number = "7",

}

TY - JOUR

T1 - Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

AU - Daruwalla, Cyrus

AU - Shaygannejad, Vahid

AU - Ozakbas, Serkan

AU - Havrdova, Eva Kubala

AU - Horakova, Dana

AU - Alroughani, Raed

AU - Boz, Cavit

AU - Patti, Francesco

AU - Onofrj, Marco

AU - Lugaresi, Alessandra

AU - Eichau, Sara

AU - Girard, Marc

AU - Prat, Alexandre

AU - Duquette, Pierre

AU - Yamout, Bassem

AU - Khoury, Samia J

AU - Sajedi, Seyed Aidin

AU - Turkoglu, Recai

AU - Altintas, Ayse

AU - Skibina, Olga

AU - Buzzard, Katherine

AU - Grammond, Pierre

AU - Karabudak, Rana

AU - van der Walt, Anneke

AU - Butzkueven, Helmut

AU - Maimone, Davide

AU - Lechner-Scott, Jeannette

AU - Soysal, Aysun

AU - John, Nevin

AU - Prevost, Julie

AU - Spitaleri, Daniele

AU - Ramo-Tello, Cristina

AU - Gerlach, Oliver

AU - Iuliano, Gerardo

AU - Foschi, Matteo

AU - Ampapa, Radek

AU - van Pesch, Vincent

AU - Barnett, Michael

AU - Shalaby, Nevin

AU - D'hooghe, Marie

AU - Kuhle, Jens

AU - Sa, Maria Jose

AU - Fabis-Pedrini, Marzena

AU - Kermode, Allan

AU - Mrabet, Saloua

AU - Gouider, Riadh

AU - Hodgkinson, Suzanne

AU - Laureys, Guy

AU - Van Hijfte, Liesbeth

AU - Macdonell, Richard

AU - Oreja-Guevara, Celia

AU - Cristiano, Edgardo

AU - McCombe, Pamela

AU - Sanchez-Menoyo, Jose Luis

AU - Singhal, Bhim

AU - Blanco, Yolanda

AU - Hughes, Stella

AU - Garber, Justin

AU - Solaro, Claudio

AU - McGuigan, Chris

AU - Taylor, Bruce

AU - de Gans, Koen

AU - Habek, Mario

AU - Al-Asmi, Abdullah

AU - Mihaela, Simu

AU - Castillo Triviño, Tamara

AU - Al-Harbi, Talal

AU - Rojas, Juan Ignacio

AU - Gray, Orla

AU - Khurana, Dheeraj

AU - Van Wijmeersch, Bart

AU - Grigoriadis, Nikolaos

AU - Inshasi, Jihad

AU - Oh, Jiwon

AU - Aguera-Morales, Eduardo

AU - Fragoso, Yara

AU - Moore, Fraser

AU - Shaw, Cameron

AU - Baghbanian, Seyed Mohammad

AU - Shuey, Neil

AU - Willekens, Barbara

AU - Hardy, Todd A

AU - Decoo, Danny

AU - Sempere, Angel Perez

AU - Field, Deborah

AU - Wynford-Thomas, Ray

AU - Cunniffe, Nick G

AU - Roos, Izanne

AU - Malpas, Charles B

AU - Coles, Alasdair J

AU - Kalincik, Tomas

AU - Brown, J William L

N1 - Funding Information: A.A. received speaker honoraria from Merck, Alexion; received travel and registration grants from Merck. Funding Information: A.L. has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme and, Teva, and Bristol Myers Squibb. Her institutions have received research grants from Novartis and Sanofi/Genzyme. Funding Information: N.G. received honoraria and travel support, Consultancy fees, Lecture fees from Biogen Idec, Biologix, Novartis, TEVA, Bayer, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE, ELPEN. Research grants from Biogen Idec, Novartis, TEVA, Merck Serono, Genesis Pharma, Sanofi – Genzyme, ROCHE Funding Information: T.C.T. received speaking/consulting fees and/or travel funding from Almirall, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Funding Information: H.B. received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers’ bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd and Merck; has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Funding Information: F.P. received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. He received research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association and University of Catania. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.K.H. received honoraria/research support from Biogen, Merck Serono, Novartis, Roche, and Teva; has been member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis, and Sanofi Genzyme. She was also supported by the Charles University: Cooperatio Program in neuroscience. D.H. received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck Healthcare KGaA (Darmstadt, Germany), Bayer, Sanofi, Roche, and Teva, as well as support for research activities from Biogen. She was also supported by the Charles University: Cooperatio Program in neuroscience. R.A. received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. C.B. received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; has participated in clinical trials by Sanofi Aventis, Roche and Novartis. Funding Information: I.R. served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck and Biogen. Izanne Roos receives research support from Multiple Sclerosis Australia and the Trish Multiple Sclerosis Research Foundation. Funding Information: M.G. received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; lecture payments from Teva Canada Innovation, Novartis and EMD . He has also received a research grant from Canadian Institutes of Health Research. Funding Information: B.W. received honoraria for acting as a member of Scientific Advisory Boards for Almirall, Biogen, Celgene/BMS, Merck Serono, Novartis, Roche, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Merck Serono, Novartis, Roche, Sanofi-Genzyme; research and/or patient support grants from Roche, Biogen, Merck-Serono, Sanofi-Genzyme; research support from FWO. Honoraria and grants were paid to UZA/UZA Foundation. Publisher Copyright: © The Author(s), 2023.

PY - 2023/6

Y1 - 2023/6

N2 - BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS.METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

AB - BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS.METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated ( n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs ( n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs ( n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

KW - Multiple sclerosis

KW - prognosis

KW - Multiple Sclerosis

KW - Recurrence

KW - Prognosis

KW - Humans

KW - Multiple Sclerosis, Relapsing-Remitting/drug therapy

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UR - http://www.scopus.com/inward/citedby.url?scp=85163913863&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/954ece60-8244-30d2-bfc8-518027bc8570/

U2 - 10.1177/13524585231151951

DO - 10.1177/13524585231151951

M3 - Article

C2 - 36851894

SN - 1352-4585

VL - 29

SP - 875

EP - 883

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 7

ER -