A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/4226 |
Resumo: | Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. Patients and methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal. |
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A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in PortugalHSAC NEUAdultFemaleMaleHumansCohort StudiesDisease Progression*Follow-Up StudiesImmunologic Factors / adverse effectsImmunologic Factors / therapeutic useMultiple Sclerosis, Relapsing-Remitting / diagnosis*Multiple Sclerosis, Relapsing-Remitting / drug therapyMultiple Sclerosis, Relapsing-Remitting / epidemiologyNatalizumab / adverse effectsNatalizumab / therapeutic use*Retrospective StudiesPortugal / epidemiologyYoung AdultWithholding Treatment / trends*Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. Patients and methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPELadeira, FBraz, LSalgado, PVaz, SLeitão, LFélix, CCorreia, ASMartins da Silva, ASalgado, VFerreira, FVale, JSá, MJCapela, C2022-08-22T15:41:20Z2019-092019-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4226engClin Neurol Neurosurg. 2019 Sep;184:105390.10.1016/j.clineuro.2019.105390.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:45:55Zoai:repositorio.chlc.min-saude.pt:10400.17/4226Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:21:33.313363Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
title |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
spellingShingle |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal Ladeira, F HSAC NEU Adult Female Male Humans Cohort Studies Disease Progression* Follow-Up Studies Immunologic Factors / adverse effects Immunologic Factors / therapeutic use Multiple Sclerosis, Relapsing-Remitting / diagnosis* Multiple Sclerosis, Relapsing-Remitting / drug therapy Multiple Sclerosis, Relapsing-Remitting / epidemiology Natalizumab / adverse effects Natalizumab / therapeutic use* Retrospective Studies Portugal / epidemiology Young Adult Withholding Treatment / trends* |
title_short |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
title_full |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
title_fullStr |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
title_full_unstemmed |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
title_sort |
A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal |
author |
Ladeira, F |
author_facet |
Ladeira, F Braz, L Salgado, P Vaz, S Leitão, L Félix, C Correia, AS Martins da Silva, A Salgado, V Ferreira, F Vale, J Sá, MJ Capela, C |
author_role |
author |
author2 |
Braz, L Salgado, P Vaz, S Leitão, L Félix, C Correia, AS Martins da Silva, A Salgado, V Ferreira, F Vale, J Sá, MJ Capela, C |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Ladeira, F Braz, L Salgado, P Vaz, S Leitão, L Félix, C Correia, AS Martins da Silva, A Salgado, V Ferreira, F Vale, J Sá, MJ Capela, C |
dc.subject.por.fl_str_mv |
HSAC NEU Adult Female Male Humans Cohort Studies Disease Progression* Follow-Up Studies Immunologic Factors / adverse effects Immunologic Factors / therapeutic use Multiple Sclerosis, Relapsing-Remitting / diagnosis* Multiple Sclerosis, Relapsing-Remitting / drug therapy Multiple Sclerosis, Relapsing-Remitting / epidemiology Natalizumab / adverse effects Natalizumab / therapeutic use* Retrospective Studies Portugal / epidemiology Young Adult Withholding Treatment / trends* |
topic |
HSAC NEU Adult Female Male Humans Cohort Studies Disease Progression* Follow-Up Studies Immunologic Factors / adverse effects Immunologic Factors / therapeutic use Multiple Sclerosis, Relapsing-Remitting / diagnosis* Multiple Sclerosis, Relapsing-Remitting / drug therapy Multiple Sclerosis, Relapsing-Remitting / epidemiology Natalizumab / adverse effects Natalizumab / therapeutic use* Retrospective Studies Portugal / epidemiology Young Adult Withholding Treatment / trends* |
description |
Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. Patients and methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-09 2019-09-01T00:00:00Z 2022-08-22T15:41:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/4226 |
url |
http://hdl.handle.net/10400.17/4226 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clin Neurol Neurosurg. 2019 Sep;184:105390. 10.1016/j.clineuro.2019.105390. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799131310862630912 |