Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Type
2.2. Data Sources
2.2.1. Medication Distribution Data by State
2.2.2. Medication Registration Data
2.2.3. Technical and Scientific Information and Indication for Use in the Medication Leaflet
2.2.4. Data on Medications Not Approved by the Brazilian Unified Health System (SUS)
2.2.5. Mechanisms of Action of Medications
2.3. Software
3. Pharmacoepidemiological Analysis
3.1. Disease-Modifying Therapies
3.2. Interferons Beta
3.3. Glatiramer Acetate
3.4. Natalizumab
3.5. Fingolimod
3.6. Alemtuzumab
3.7. Teriflunomide
3.8. Dimethyl Fumarate
3.9. Ocrelizumab
3.10. Cladribine
3.11. Ofatumumab
3.12. Siponimod
3.13. Other Drug Therapies
3.14. Hospitalizations and Deaths
3.15. Lead Time of Free Distribution
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kornek, B.; Storch, M.K.; Weissert, R.; Wallstroem, E.; Stefferl, A.; Olsson, T.; Linington, C.; Schmidbauer, M.; Lassmann, H.J.T. Multiple sclerosis and chronic autoimmune encephalomyelitis: A comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol. 2000, 157, 267–276. [Google Scholar] [CrossRef]
- Kamm, C.P.; Uitdehaag, B.M.; Polman, C.H. Multiple sclerosis: Current knowledge and future outlook. Eur. Neurol. 2014, 72, 132–141. [Google Scholar] [CrossRef]
- Arnold, A.C. Evolving management of optic neuritis and multiple sclerosis. Am. J. Ophthalmol. 2005, 139, 1101–1108. [Google Scholar] [CrossRef]
- Ebers, G. Neurosurgery; Psychiatry. Natural history of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2001, 71, ii16–ii19. [Google Scholar]
- Soelberg Sorensen, P. Safety concerns and risk management of multiple sclerosis therapies. Acta Neurol. Scand. 2017, 136, 168–186. [Google Scholar] [CrossRef]
- Thompson, A.J.; Polman, C.H.; Miller, D.H.; McDonald, W.I.; Brochet, B.; Filippi MMontalban, X.; De Sa, J. Primary progressive multiple sclerosis. Brain J. Neurol. 1997, 120, 1085–1096. [Google Scholar] [CrossRef]
- Milo, R.; Miller, A. Revised diagnostic criteria of multiple sclerosis. Autoimmun. Rev. 2014, 13, 518–524. [Google Scholar] [CrossRef]
- Milo, R.; Kahana, E. Multiple sclerosis: Geoepidemiology, genetics and the environment. Autoimmun. Rev. 2010, 9, A387–A394. [Google Scholar] [CrossRef]
- Correale, J.; Ysrraelit, M.C.; Fiol, M.P. Benign multiple sclerosis: Does it exist? Curr. Neurol. Neurosci. Rep. 2012, 12, 601–609. [Google Scholar] [CrossRef]
- Stinissen, P.; Raus, J.; Zhang, J. Autoimmune pathogenesis of multiple sclerosis: Role of autoreactive T lymphocytes and new immunotherapeutic strategies. Crit. Rev. Immunol. 1997, 17, 33–75. [Google Scholar] [CrossRef]
- Institute of Medicine (US) Committee on Multiple Sclerosis. Multiple Sclerosis: Current Status and Strategies for the Future; Joy, J.E., Johnston, R.B., Jr., Eds.; The National Academies Press: Washington, DC, USA, 2001; p. 456. [Google Scholar]
- Lucchinetti, C.F.; Brück, W.; Rodriguez, M.; Lassmann, H. Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis. Brain Pathol. 1996, 6, 259–274. [Google Scholar] [CrossRef]
- Brazil, Ministério da Saúde. Clinical Protocols and Therapeutic Guidelines for Multiple Sclerosis. 2022. Available online: https://www.gov.br/saude/pt-br/assuntos/protocolos-clinicos-e-diretrizes-terapeuticas-pcdt/arquivos/2022/portal_portaria-conjunta-no-1-pcdt_esclerose-multipla.pdf (accessed on 13 August 2023).
- Lenne, B.; Donze, C.; Massot, C.; Degraeve, B. Impact of physical activity, physical fitness and exercises on cognitive impairment in patients with multiple sclerosis: A review of evidence and underlying mechanisms. Rev. Neurol. 2023. [Google Scholar] [CrossRef]
- Okemuo, A.J.; Gallagher, D.; Dairo, Y.M. Effects of rebound exercises on balance and mobility of people with neurological disorders: A systematic review. PLoS ONE 2023, 18, e0292312. [Google Scholar] [CrossRef]
- Loma, I.; Heyman, R. Multiple sclerosis: Pathogenesis and treatment. Curr. Neuropharmacol. 2011, 9, 409–416. [Google Scholar] [CrossRef]
- Beck, R.W.; Cleary, P.A.; Trobe, J.D.; Kaufman, D.I.; Kupersmith, M.J.; Paty, D.W.; Brown, C.H. The Effect of Corticosteroids for Acute Optic Neuritis on the Subsequent Development of Multiple Sclerosis. N. Engl. J. Med. 1993, 329, 1764–1769. [Google Scholar] [CrossRef]
- Goldenberg, M.M. Therapeutics. Mult. Scler. Rev. 2012, 37, 175. [Google Scholar]
- Callegari, I.; Derfuss, T.; Galli, E. Update on treatment in multiple sclerosis. Presse Med. 2021, 50, 104068. [Google Scholar] [CrossRef]
- Wingerchuk, D.M.; Weinshenker, B.G. Disease modifying therapies for relapsing multiple sclerosis. BMJ 2016, 354, i3518. [Google Scholar] [CrossRef]
- Schrempf, W.; Ziemssen, T. Glatiramer acetate: Mechanisms of action in multiple sclerosis. Autoimmun. Rev. 2007, 6, 469–475. [Google Scholar] [CrossRef]
- Papadopoulou, A.; D’Souza, M.; Kappos, L.; Yaldizli, O. Dimethyl fumarate for multiple sclerosis. Expert. Opin. Investig. Drugs 2010, 19, 1603–1612. [Google Scholar] [CrossRef]
- Miller, A.E. An updated review of teriflunomide’s use in multiple sclerosis. Neurodegener. Dis. Manag. 2021, 11, 387–409. [Google Scholar] [CrossRef]
- Kappos, L. Interferons in multiple sclerosis. Neurol. Clin. 2005, 23, 189–214. [Google Scholar] [CrossRef]
- Pelletier, D.; Hafler, D.A. Fingolimod for multiple sclerosis. N. Engl. J. Med. 2012, 366, 339–347. [Google Scholar] [CrossRef]
- Voge, N.V.; Alvarez, E. Monoclonal Antibodies in Multiple Sclerosis: Present and Future. Biomedicines 2019, 7, 20. [Google Scholar] [CrossRef]
- McGinley, M.P.; Goldschmidt, C.H.; Rae-Grant, A.D. Diagnosis and Treatment of Multiple Sclerosis: A Review. JAMA 2021, 325, 765–779. [Google Scholar] [CrossRef]
- Stamatellos, V.P.; Papazisis, G. Safety and Monitoring of the Treatment with Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS). Curr. Rev. Clin. Exp. Pharmacol. 2023, 18, 39–50. [Google Scholar] [CrossRef]
- Travers, B.S.; Tsang, B.K.; Barton, J.L. Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis. Aust. J. Gen. Pract. 2022, 51, 199–206. [Google Scholar] [CrossRef]
- Krajnc, N.; Bsteh, G.; Berger, T.; Mares, J.; Hartung, H.P. Monoclonal Antibodies in the Treatment of Relapsing Multiple Sclerosis: An Overview with Emphasis on Pregnancy, Vaccination, and Risk Management. Neurotherapeutics 2022, 19, 753–773. [Google Scholar] [CrossRef]
- McGinley, M.P.; Moss, B.P.; Cohen, J.A. Safety of monoclonal antibodies for the treatment of multiple sclerosis. Expert. Opin. Drug Saf. 2017, 16, 89–100. [Google Scholar] [CrossRef]
- Graf, J.; Aktas, O.; Rejdak, K.; Hartung, H.P. Monoclonal Antibodies for Multiple Sclerosis: An Update. BioDrugs 2019, 33, 61–78. [Google Scholar] [CrossRef]
- Palavra, F. Monoclonal Antibodies for Multiple Sclerosis Treatment. Acta Med. Port. 2015, 28, 640–651. [Google Scholar] [CrossRef] [PubMed]
- Haghikia, A.; Faissner, S.; Pappas, D.; Pula, B.; Akkad, D.A.; Arning, L.; Ruhrmann, S.; Duscha, A.; Gold, R.; Baranzini, S.E.; et al. Interferon-beta affects mitochondrial activity in CD4+ lymphocytes: Implications for mechanism of action in multiple sclerosis. Mult. Scler. 2015, 21, 1262–1270. [Google Scholar] [CrossRef] [PubMed]
- Markowitz, C.E. Interferon-beta: Mechanism of action and dosing issues. Neurology 2007, 68, S8–S11. [Google Scholar] [CrossRef]
- Kieseier, B.C. The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs 2011, 25, 491–502. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Interferon Beta-1b. Available online: https://consultas.anvisa.gov.br/#/medicamentos/250000045539641/?substancia=23121 (accessed on 19 August 2023).
- REBIF. Prescribing Information. Bayer S.A. São Paulo, Brasil. 2022. Available online: https://consultas.anvisa.gov.br/#/bulario/q/?nomeProduto=Betaferon (accessed on 13 August 2023).
- ANVISA. Medication Registration Search—Interferon Beta-1a. Available online: https://consultas.anvisa.gov.br/#/medicamentos/250000122709411/?substancia=23047 (accessed on 19 August 2023).
- REBIF. Prescribing Information. MERCK S.A. Rio de Janeiro, Brasil. 2021. Available online: https://www.merckgroup.com/br-pt/bulario/Rebif_Bula_Profissional_290421.pdf (accessed on 13 August 2023).
- Saúde, M.d. Access to Brazilian Health System (SUS) Data Information. Available online: https://datasus.saude.gov.br/acesso-a-informacao/producao-ambulatorial-sia-sus/ (accessed on 13 August 2023).
- Astrom, M.E.; Roos, P.M. Geochemistry of multiple sclerosis in Finland. Sci. Total Environ. 2022, 841, 156672. [Google Scholar] [CrossRef]
- Krokki, O.; Bloigu, R.; Reunanen, M.; Remes, A.M. Increasing incidence of multiple sclerosis in women in Northern Finland. Mult. Scler. 2011, 17, 133–138. [Google Scholar] [CrossRef]
- Sharpe, R.J. The low incidence of multiple sclerosis in areas near the equator may be due to ultraviolet light induced suppressor cells to melanocyte antigens. Med. Hypotheses 1986, 19, 319–323. [Google Scholar] [CrossRef]
- Teitelbaum, D.; Meshorer, A.; Hirshfeld, T.; Arnon, R.; Sela, M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur. J. Immunol. 1971, 1, 242–248. [Google Scholar] [CrossRef]
- Blanchette, F.; Neuhaus, O. Glatiramer acetate: Evidence for a dual mechanism of action. J. Neurol. 2008, 255 (Suppl. S1), 26–36. [Google Scholar] [CrossRef]
- Carter, N.J.; Keating, G.M. Glatiramer acetate: A review of its use in relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis. Drugs 2010, 70, 1545–1577. [Google Scholar] [CrossRef]
- Kasindi, A.; Fuchs, D.T.; Koronyo, Y.; Rentsendorj, A.; Black, K.L.; Koronyo-Hamaoui, M. Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and Cognitive Preservation. Cells 2022, 11, 1578. [Google Scholar] [CrossRef]
- Simpson, D.; Noble, S.; Perry, C. Glatiramer acetate: A review of its use in relapsing-remitting multiple sclerosis. CNS Drugs 2002, 16, 825–850. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Glatiramer Acetate. Available online: https://consultas.anvisa.gov.br/#/medicamentos/250000267069765/?substancia=20698 (accessed on 19 August 2023).
- Consultas. Prescribing Information. Teva Farmacêutica Ltd.a. São Paulo, Brasil. 2023. Available online: https://consultas.anvisa.gov.br/#/bulario/q/?numeroRegistro=155730001 (accessed on 13 August 2023).
- Morrow, S.A.; Clift, F.; Devonshire, V.; Lapointe, E.; Schneider, R.; Stefanelli, M.; Vosoughi, R. Use of natalizumab in persons with multiple sclerosis: 2022 update. Mult. Scler. Relat. Disord. 2022, 65, 103995. [Google Scholar] [CrossRef]
- Sellner, J.; Rommer, P.S. A review of the evidence for a natalizumab exit strategy for patients with multiple sclerosis. Autoimmun. Rev. 2019, 18, 255–261. [Google Scholar] [CrossRef]
- Outteryck, O. Natalizumab in relapsing-remitting multiple sclerosis. Expert. Rev. Neurother. 2016, 16, 471–481. [Google Scholar] [CrossRef]
- Gandhi, S.; Jakimovski, D.; Ahmed, R.; Hojnacki, D.; Kolb, C.; Weinstock-Guttman, B.; Zivadinov, R. Use of natalizumab in multiple sclerosis: Current perspectives. Expert. Opin. Biol. Ther. 2016, 16, 1151–1162. [Google Scholar] [CrossRef] [PubMed]
- Shirani, A.; Stuve, O. Natalizumab for Multiple Sclerosis: A Case in Point for the Impact of Translational Neuroimmunology. J. Immunol. 2017, 198, 1381–1386. [Google Scholar] [CrossRef]
- Khoy, K.; Mariotte, D.; Defer, G.; Petit, G.; Toutirais, O.; Le Mauff, B. Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring. Front. Immunol. 2020, 11, 549842. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Natalizumab. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351216949200755/?substancia=23613 (accessed on 19 August 2023).
- TYSABRI Natalizumabe. Prescribing Information. Biogen Brasil Produtos Farmacêuticos Ltd.a. São Paulo, Brasil. 2022. Available online: https://br.biogen.com/content/dam/corporate/americas/brazil/pt-br/pdf-medicines/tysabri_natalizumabe_bula_profissional.pdf (accessed on 13 August 2023).
- Chun, J.; Hartung, H.P. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin. Neuropharmacol. 2010, 33, 91–101. [Google Scholar] [CrossRef]
- Cohen, J.A.; Chun, J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann. Neurol. 2011, 69, 759–777. [Google Scholar] [CrossRef]
- Tanasescu, R.; Constantinescu, C.S. Pharmacokinetic evaluation of fingolimod for the treatment of multiple sclerosis. Expert. Opin. Drug Metab. Toxicol. 2014, 10, 621–630. [Google Scholar] [CrossRef]
- Yang, T.; Tian, X.; Chen, C.Y.; Ma, L.Y.; Zhou, S.; Li, M.; Wu, Y.; Zhou, Y.; Cui, Y.M. The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta-analysis. Br. J. Clin. Pharmacol. 2020, 86, 637–645. [Google Scholar] [CrossRef]
- Ziemssen, T.; Medin, J.; Couto, C.A.; Mitchell, C.R. Multiple sclerosis in the real world: A systematic review of fingolimod as a case study. Autoimmun. Rev. 2017, 16, 355–376. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Fingolimod. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351190569201016/?substancia=25273 (accessed on 19 August 2023).
- GILENYA Cloridrato de Fingolimode. Prescribing Information. Novartis Biociências S.A. São Paulo, Brasil. 2023. Available online: https://portal.novartis.com.br/medicamentos/wp-content/uploads/2021/10/Bula-GILENYA-Capsula-Dura-Medico.pdf (accessed on 13 August 2023).
- Katsavos, S.; Coles, A. Alemtuzumab as Treatment for Multiple Sclerosis. Cold Spring Harb. Perspect. Med. 2018, 8. [Google Scholar] [CrossRef]
- Evan, J.R.; Bozkurt, S.B.; Thomas, N.C.; Bagnato, F. Alemtuzumab for the treatment of multiple sclerosis. Expert. Opin. Biol. Ther. 2018, 18, 323–334. [Google Scholar] [CrossRef]
- Syed, Y.Y. Alemtuzumab: A Review in Relapsing Remitting Multiple Sclerosis. Drugs 2021, 81, 157–168. [Google Scholar] [CrossRef]
- Riera, R.; Porfirio, G.J.; Torloni, M.R. Alemtuzumab for multiple sclerosis. Cochrane Database Syst. Rev. 2016, 4, CD011203. [Google Scholar] [CrossRef]
- Willis, M.D.; Robertson, N.P. Alemtuzumab for Multiple Sclerosis. Curr. Neurol. Neurosci. Rep. 2016, 16, 84. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Alemtuzumab. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351730256201318/?substancia=23547 (accessed on 19 August 2023).
- LEMTRADA. Prescribing Information. Sanofi Medley Farmacêutica Ltd.a. São Paulo, Brasil. 2023. Available online: https://sm.far.br/pdfshow/bula_183260349_0437889238_p.pdf (accessed on 13 August 2023).
- Garnock-Jones, K.P. Teriflunomide: A review of its use in relapsing multiple sclerosis. CNS Drugs 2013, 27, 1103–1123. [Google Scholar] [CrossRef] [PubMed]
- He, D.; Zhang, C.; Zhao, X.; Zhang, Y.; Dai, Q.; Li, Y.; Chu, L. Teriflunomide for multiple sclerosis. Cochrane Database Syst. Rev. 2016, 3, CD009882. [Google Scholar] [CrossRef]
- Chan, A.; de Seze, J.; Comabella, M. Teriflunomide in Patients with Relapsing-Remitting Forms of Multiple Sclerosis. CNS Drugs 2016, 30, 41–51. [Google Scholar] [CrossRef]
- Hauser, S.L.; Bar-Or, A.; Cohen, J.A.; Comi, G.; Correale, J.; Coyle, P.K.; Cross, A.H.; de Seze, J.; Leppert, D.; Montalban, X.; et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N. Engl. J. Med. 2020, 383, 546–557. [Google Scholar] [CrossRef]
- He, D.; Xu, Z.; Dong, S.; Zhang, H.; Zhou, H.; Wang, L.; Zhang, S. Teriflunomide for multiple sclerosis. Cochrane Database Syst. Rev. 2012, 12, CD009882. [Google Scholar] [CrossRef]
- Scott, L.J. Teriflunomide: A Review in Relapsing-Remitting Multiple Sclerosis. Drugs 2019, 79, 875–886. [Google Scholar] [CrossRef]
- Aubagio® (Teriflunomide))—Prescribing Information. Sanofi Medley Farmacêutica Ltd.a. São Paulo. Prescribing information. Sanofi Medley Farmacêutica Ltd.a. São Paulo, Brasil. 2022. Available online: https://sm.far.br/pdfshow/bula_183260315_0542511223_p.pdf (accessed on 13 August 2023).
- ANVISA. Medication Registration Search—Teriflunomide. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351686962201130/?substancia=24271 (accessed on 19 August 2023).
- Xu, Z.; Zhang, F.; Sun, F.; Gu, K.; Dong, S.; He, D. Dimethyl fumarate for multiple sclerosis. Cochrane Database Syst. Rev. 2015, 2015, CD011076. [Google Scholar] [CrossRef]
- Suneetha, A.; Raja Rajeswari, K. Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2016, 1019, 15–20. [Google Scholar] [CrossRef]
- Blair, H.A. Dimethyl Fumarate: A Review in Relapsing-Remitting MS. Drugs 2019, 79, 1965–1976. [Google Scholar] [CrossRef] [PubMed]
- Dias de Sousa, M.A.; Desiderio, C.S.; da Silva Catarino, J.; Trevisan, R.O.; Alves da Silva, D.A.; Rocha, V.F.R.; Bovi, W.G.; Timoteo, R.P.; Bonatti, R.C.F.; da Silva, A.E.; et al. Role of Cytokines, Chemokines and IFN-gamma+ IL-17+ Double-Positive CD4+ T Cells in Patients with Multiple Sclerosis. Biomedicines 2022, 10, 2062. [Google Scholar] [CrossRef]
- Dello Russo, C.; Scott, K.A.; Pirmohamed, M. Dimethyl fumarate induced lymphopenia in multiple sclerosis: A review of the literature. Pharmacol. Ther. 2021, 219, 107710. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Dimethyl Fumarate. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351186118201351/?substancia=25886 (accessed on 17 August 2023).
- TECFIDERA® Fumarato de Dimetila. Prescribing Information. Biogen Brasil Produtos Farmacêuticos Ltd.a. São Paulo, Brasil. 2022. Available online: https://br.biogen.com/content/dam/corporate/americas/brazil/pt-br/pdf-medicines/tecfidera_fumarato_de_dimetila_bula_profissional_de_saude.pdf (accessed on 13 August 2023).
- Bigaut, K.; De Seze, J.; Collongues, N. Ocrelizumab for the treatment of multiple sclerosis. Expert. Rev. Neurother. 2019, 19, 97–108. [Google Scholar] [CrossRef]
- Sorensen, P.S.; Blinkenberg, M. The potential role for ocrelizumab in the treatment of multiple sclerosis: Current evidence and future prospects. Ther. Adv. Neurol. Disord. 2016, 9, 44–52. [Google Scholar] [CrossRef]
- Mancinelli, C.R.; Rossi, N.; Capra, R. Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology. Ther. Clin. Risk Manag. 2021, 17, 765–776. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Ocrelizumab. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351195147201723/?substancia=26228 (accessed on 19 August 2023).
- Ocrevus. Prescribing Information. Produtos Roche Químicos e Farmacêuticos S.A. São Paulo, Brasil. 2023. Available online: https://dialogoroche.com.br/content/dam/roche-dialogo/dialogo-brazil-assets/downloadable-assets/produtos/bulas/ocrevus/Ocrevus_Bula_do_Profissional.pdf (accessed on 13 August 2023).
- CONITEC., M.d.S. Ocrelizumabe Para Tratamento de Pacientes Adultos com Esclerose Múltipla Remitente-Recorrente (EMRR) Como Alternativa ou Contraindicação ao Natalizumabe. Available online: https://www.gov.br/conitec/pt-br/midias/consultas/relatorios/2020/relatorio_inicial_ocrelizumabe_emrr_cp36_2020.pdf (accessed on 13 August 2023).
- Biernacki, T.; Sandi, D.; Bencsik, K.; Vecsei, L. Medicinal Chemistry of Multiple Sclerosis: Focus on Cladribine. Mini Rev. Med. Chem. 2020, 20, 269–285. [Google Scholar] [CrossRef] [PubMed]
- Giovannoni, G.; Soelberg Sorensen, P.; Cook, S.; Rammohan, K.; Rieckmann, P.; Comi, G.; Dangond, F.; Adeniji, A.K.; Vermersch, P. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult. Scler. 2018, 24, 1594–1604. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, B.M.; Ammoscato, F.; Giovannoni, G.; Baker, D.; Schmierer, K. Cladribine: Mechanisms and mysteries in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2018, 89, 1266–1271. [Google Scholar] [CrossRef]
- Comi, G.; Cook, S.; Giovannoni, G.; Rieckmann, P.; Sorensen, P.S.; Vermersch, P.; Galazka, A.; Nolting, A.; Hicking, C.; Dangond, F. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult. Scler. Relat. Disord. 2019, 29, 168–174. [Google Scholar] [CrossRef]
- Giovannoni, G.; Mathews, J. Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician’s Review. Neurol. Ther. 2022, 11, 571–595. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Cladribine. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351497138201717/?substancia=2166 (accessed on 23 August 2023).
- MAVENCLAD® Cladribina. Prescribing Information. MERCK S.A. Rio de Janeiro, Brasil. 2019. Available online: https://www.merckgroup.com/br-pt/bulario/Mavenclad_Bula%20Profissional_pr%C3%A9-lan%C3%A7amento.pdf (accessed on 13 August 2023).
- Ministério da Saúde—CONITEC. Cladribina Oral No Tratamento de Pacientes Com Esclerose Múltipla Remitente-Recorrente Altamente Ativa. Available online: https://www.gov.br/conitec/pt-br/midias/consultas/relatorios/2023/20230725_relatorio_cp_cladribina_emrr.pdf/view (accessed on 13 August 2023).
- Sanford, M.; McCormack, P.L. Ofatumumab. Drugs 2010, 70, 1013–1019. [Google Scholar] [CrossRef]
- Kang, C.; Blair, H.A. Ofatumumab: A Review in Relapsing Forms of Multiple Sclerosis. Drugs 2022, 82, 55–62. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Ofatumumab. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351481485202023/?substancia=25320 (accessed on 19 August 2023).
- KESIMPTA. Prescribing Information. Novartis Biociências S.A. São Paulo, Brasil. 2023. Available online: https://portal.novartis.com.br/medicamentos/wp-content/uploads/2021/10/Bula-KESIMPTA-Solucao-injetavel-Medico.pdf (accessed on 13 August 2023).
- Ministério da Saúde—CONITEC. Ofatumumabe em Primeira Linha de Terapia Modificadora do Curso da Doença Para o Tratamento da Esclerose Múltipla Recorrente. Available online: http://antigo-conitec.saude.gov.br/images/Consultas/Relatorios/2022/20220401_Relatorio_CP_12_Ofatumumabe_esclerose_multipla_recorrente.pdf (accessed on 13 August 2023).
- Scott, L.J. Siponimod: A Review in Secondary Progressive Multiple Sclerosis. CNS Drugs 2020, 34, 1191–1200. [Google Scholar] [CrossRef]
- Goodman, A.D.; Anadani, N.; Gerwitz, L. Siponimod in the treatment of multiple sclerosis. Expert. Opin. Investig. Drugs 2019, 28, 1051–1057. [Google Scholar] [CrossRef]
- Kappos, L.; Bar-Or, A.; Cree, B.A.C.; Fox, R.J.; Giovannoni, G.; Gold, R.; Vermersch, P.; Arnold, D.L.; Arnould, S.; Scherz, T.; et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): A double-blind, randomised, phase 3 study. Lancet 2018, 391, 1263–1273. [Google Scholar] [CrossRef]
- Benedict, R.H.B.; Tomic, D.; Cree, B.A.; Fox, R.; Giovannoni, G.; Bar-Or, A.; Gold, R.; Vermersch, P.; Pohlmann, H.; Wright, I.; et al. Siponimod and Cognition in Secondary Progressive Multiple Sclerosis: EXPAND Secondary Analyses. Neurology 2021, 96, e376–e386. [Google Scholar] [CrossRef]
- Cao, L.; Li, M.; Yao, L.; Yan, P.; Wang, X.; Yang, Z.; Lao, Y.; Li, H.; Yang, K.; Li, K. Siponimod for multiple sclerosis. Cochrane Database Syst. Rev. 2021, 11, CD013647. [Google Scholar] [CrossRef]
- Gajofatto, A.; Turatti, M. Siponimod to treat secondary progressive multiple sclerosis. Drugs Today 2020, 56, 37–46. [Google Scholar] [CrossRef]
- ANVISA. Medication Registration Search—Siponimod. Available online: https://consultas.anvisa.gov.br/#/medicamentos/25351780309202071/?substancia=26514 (accessed on 2 August 2023).
- K.S. Prescribing Information. Novartis Biociências S.A. São Paulo, Brasil. 2023. Available online: https://portal.novartis.com.br/medicamentos/wp-content/uploads/2022/10/Bula-KIENDRA-Comprimido-Revestido-Medico.pdf (accessed on 13 August 2023).
- Fox, E.J. Management of worsening multiple sclerosis with mitoxantrone: A review. Clin. Ther. 2006, 28, 461–474. [Google Scholar] [CrossRef]
- Gonsette, R.E. Mitoxantrone immunotherapy in multiple sclerosis. Mult. Scler. 1996, 1, 329–332. [Google Scholar] [CrossRef]
- Cocco, E.; Marrosu, M.G. The current role of mitoxantrone in the treatment of multiple sclerosis. Expert. Rev. Neurother. 2014, 14, 607–616. [Google Scholar] [CrossRef]
- Martinelli Boneschi, F.; Vacchi, L.; Rovaris, M.; Capra, R.; Comi, G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst. Rev. 2013, 2013, CD002127. [Google Scholar] [CrossRef]
- Buttmann, M. Where mitoxantrone for multiple sclerosis is still valuable in 2018. Eur. J. Neurol. 2018, 25, 1400–1401. [Google Scholar] [CrossRef]
- Gonsette, R.E. Mitoxantrone in progressive multiple sclerosis: When and how to treat? J. Neurol. Sci. 2003, 206, 203–208. [Google Scholar] [CrossRef]
- Chisari, C.G.; Sgarlata, E.; Arena, S.; Toscano, S.; Luca, M.; Patti, F. Rituximab for the treatment of multiple sclerosis: A review. J. Neurol. 2022, 269, 159–183. [Google Scholar] [CrossRef]
- Ineichen, B.V.; Moridi, T.; Granberg, T.; Piehl, F. Rituximab treatment for multiple sclerosis. Mult. Scler. 2020, 26, 137–152. [Google Scholar] [CrossRef]
- Kitsos, D.K.; Tsiodras, S.; Stamboulis, E.; Voumvourakis, K.I. Rituximab and multiple sclerosis. Clin. Neuropharmacol. 2012, 35, 90–96. [Google Scholar] [CrossRef] [PubMed]
- Midaglia Fernández, L.; Mora, L.; Mulero Carrillo, P.; Sastre Garriga, J.; Montalban Gairin, X. Rituximab: Eficacia, efectividad y seguridad en el tratamiento de la esclerosis múltiple. Rev. Neurol. 2018, 66, 25. [Google Scholar] [CrossRef]
DMT Category | DMT | Mechanism of Action | Treatment Line a | ||
---|---|---|---|---|---|
Low/Moderate Activity | High Activity | Registration f | |||
Injectable DMTs | INF-ß-1B | Reduces the activity of immune cells involved in CNS inflammation | First-line | 1996 | |
INF-ß-1A | Reduces the activity of immune cells involved in CNS inflammation | First-line | 1996 | ||
Glatiramer acetate | Induces suppressor T lymphocytes (Th2 profile), inhibiting inflammation in CNS | First-line | 1998 | ||
Oral DMTs | Fingolimod b | Affects G protein-coupled S1P receptors | Second-line c | 2011 | |
Teriflunomide | Inhibits pyrimidine synthesis (dihydroorotate dehydrogenase) | First-line | 2014 | ||
Dimethyl fumarate | Causes selective immunosuppression affecting T/B cells | First-line | 2015 | ||
Cladribine * | Reduces the population of T/B cells | 2019 | |||
Siponimod * | Regulates S1P1/S1P5 receptors; S1P antagonist | 2021 | |||
MAbs | Natalizumab | Inhibits migration of activated T cells across the blood–brain barrier | Third-line d | First-line | 2008 |
Alemtuzumab | Binds to CD52 on T/B cells; depletion of activated T/B cells | Second-line e | 2014 | ||
Ocrelizumab * | Induces B cell depletion | 2018 | |||
Ofatumumab * | Selectively binds to CD20 in B cells | 2021 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Desidério, C.S.; Pessoa-Gonçalves, Y.M.; Trevisan, R.O.; Dias-Sousa, M.A.; Bovi, W.G.; Rodrigues, W.F.; da Silva, M.V.; Júnior, V.R.; Oliveira, C.J.F. Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis. Sclerosis 2024, 2, 13-41. https://doi.org/10.3390/sclerosis2010003
Desidério CS, Pessoa-Gonçalves YM, Trevisan RO, Dias-Sousa MA, Bovi WG, Rodrigues WF, da Silva MV, Júnior VR, Oliveira CJF. Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis. Sclerosis. 2024; 2(1):13-41. https://doi.org/10.3390/sclerosis2010003
Chicago/Turabian StyleDesidério, Chamberttan Souza, Yago Marcos Pessoa-Gonçalves, Rafael Obata Trevisan, Marlos Aureliano Dias-Sousa, Weslley Guimarães Bovi, Wellington Francisco Rodrigues, Marcos Vinicius da Silva, Virmondes Rodrigues Júnior, and Carlo José Freire Oliveira. 2024. "Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis" Sclerosis 2, no. 1: 13-41. https://doi.org/10.3390/sclerosis2010003