Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study

Detalhes bibliográficos
Autor(a) principal: Kathiaja Miranda Souza
Data de Publicação: 2020
Outros Autores: Isabela Maia Diniz, Lívia Lovato Pires de Lemos, Nélio Gomes Ribeiro Junior, Isabella de Figueiredo Zuppo, Juliana Alvares Teodoro, Francisco de Assis Acurcio, Álvaro Nagib Atallah, Augusto Afonso Guerra Júnior
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: https://doi.org/10.1371/journal.pone.0238476
http://hdl.handle.net/1843/56588
https://orcid.org/0000-0002-9054-4794
https://orcid.org/0000-0003-2769-4615
https://orcid.org/0000-0001-6185-2686
https://orcid.org/0000-0003-0473-264X
https://orcid.org/0000-0002-0210-0721
https://orcid.org/0000-0002-5880-5261
https://orcid.org/0000-0003-0890-594X
https://orcid.org/0000-0001-5256-0577
Resumo: Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). Methods and findings We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan–Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis—HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. Conclusions This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.
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spelling 2023-07-18T16:48:48Z2023-07-18T16:48:48Z2020159116https://doi.org/10.1371/journal.pone.02384761932-6203http://hdl.handle.net/1843/56588https://orcid.org/0000-0002-9054-4794https://orcid.org/0000-0003-2769-4615https://orcid.org/0000-0001-6185-2686https://orcid.org/0000-0003-0473-264Xhttps://orcid.org/0000-0002-0210-0721https://orcid.org/0000-0002-0210-0721https://orcid.org/0000-0002-5880-5261https://orcid.org/0000-0003-0890-594Xhttps://orcid.org/0000-0001-5256-0577Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). Methods and findings We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan–Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis—HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. Conclusions This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.porUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE FARMÁCIA SOCIALPLOS ONESaúde ColetivaEficáciaEsclerose multiplaEffectivenessMultiple sclerosisNon-concurrent cohortEffectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238476Kathiaja Miranda SouzaIsabela Maia DinizLívia Lovato Pires de LemosNélio Gomes Ribeiro JuniorIsabella de Figueiredo ZuppoJuliana Alvares TeodoroFrancisco de Assis AcurcioÁlvaro Nagib AtallahAugusto Afonso Guerra Júniorinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56588/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALEffectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil A 16-year non-concurrent cohort study.pdfEffectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil A 16-year non-concurrent cohort study.pdfapplication/pdf33256989https://repositorio.ufmg.br/bitstream/1843/56588/2/Effectiveness%20of%20first-line%20treatment%20for%20relapsing-remitting%20multiple%20sclerosis%20in%20Brazil%20A%2016-year%20non-concurrent%20cohort%20study.pdfad532952b1a838eb9a01b4ec8b2b9dfeMD521843/565882023-07-18 13:48:48.599oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-18T16:48:48Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
title Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
spellingShingle Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
Kathiaja Miranda Souza
Effectiveness
Multiple sclerosis
Non-concurrent cohort
Saúde Coletiva
Eficácia
Esclerose multipla
title_short Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
title_full Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
title_fullStr Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
title_full_unstemmed Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
title_sort Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: a 16-year non-concurrent cohort study
author Kathiaja Miranda Souza
author_facet Kathiaja Miranda Souza
Isabela Maia Diniz
Lívia Lovato Pires de Lemos
Nélio Gomes Ribeiro Junior
Isabella de Figueiredo Zuppo
Juliana Alvares Teodoro
Francisco de Assis Acurcio
Álvaro Nagib Atallah
Augusto Afonso Guerra Júnior
author_role author
author2 Isabela Maia Diniz
Lívia Lovato Pires de Lemos
Nélio Gomes Ribeiro Junior
Isabella de Figueiredo Zuppo
Juliana Alvares Teodoro
Francisco de Assis Acurcio
Álvaro Nagib Atallah
Augusto Afonso Guerra Júnior
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Kathiaja Miranda Souza
Isabela Maia Diniz
Lívia Lovato Pires de Lemos
Nélio Gomes Ribeiro Junior
Isabella de Figueiredo Zuppo
Juliana Alvares Teodoro
Francisco de Assis Acurcio
Álvaro Nagib Atallah
Augusto Afonso Guerra Júnior
dc.subject.por.fl_str_mv Effectiveness
Multiple sclerosis
Non-concurrent cohort
topic Effectiveness
Multiple sclerosis
Non-concurrent cohort
Saúde Coletiva
Eficácia
Esclerose multipla
dc.subject.other.pt_BR.fl_str_mv Saúde Coletiva
Eficácia
Esclerose multipla
description Background Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). Methods and findings We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan–Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis—HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. Conclusions This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2023-07-18T16:48:48Z
dc.date.available.fl_str_mv 2023-07-18T16:48:48Z
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/1843/56588
dc.identifier.doi.pt_BR.fl_str_mv https://doi.org/10.1371/journal.pone.0238476
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.orcid.pt_BR.fl_str_mv https://orcid.org/0000-0002-9054-4794
https://orcid.org/0000-0003-2769-4615
https://orcid.org/0000-0001-6185-2686
https://orcid.org/0000-0003-0473-264X
https://orcid.org/0000-0002-0210-0721
https://orcid.org/0000-0002-0210-0721
https://orcid.org/0000-0002-5880-5261
https://orcid.org/0000-0003-0890-594X
https://orcid.org/0000-0001-5256-0577
url https://doi.org/10.1371/journal.pone.0238476
http://hdl.handle.net/1843/56588
https://orcid.org/0000-0002-9054-4794
https://orcid.org/0000-0003-2769-4615
https://orcid.org/0000-0001-6185-2686
https://orcid.org/0000-0003-0473-264X
https://orcid.org/0000-0002-0210-0721
https://orcid.org/0000-0002-5880-5261
https://orcid.org/0000-0003-0890-594X
https://orcid.org/0000-0001-5256-0577
identifier_str_mv 1932-6203
dc.language.iso.fl_str_mv por
language por
dc.relation.ispartof.pt_BR.fl_str_mv PLOS ONE
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.publisher.initials.fl_str_mv UFMG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv FAR - DEPARTAMENTO DE FARMÁCIA SOCIAL
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
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instname_str Universidade Federal de Minas Gerais (UFMG)
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institution UFMG
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