Skip to main content
Top
Published in: BMC Neurology 1/2022

Open Access 01-12-2022 | Multiple Sclerosis | Research

Comparison of dimethyl fumarate and interferon outcomes in an MS cohort

Authors: Neda Sattarnezhad, Brian C. Healy, Moogeh Baharnoori, Camilo Diaz-Cruz, James Stankiewicz, Howard L. Weiner, Tanuja Chitnis

Published in: BMC Neurology | Issue 1/2022

Login to get access

Abstract

Background

To compare the effectiveness of dimethyl fumarate (DMF) with subcutaneous interferon beta-1a (IFNβ-1a) in controlling disease activity in patients with relapsing–remitting Multiple Sclerosis (MS).

Methods

Clinical and imaging data from patients treated with either IFNβ-1a or DMF for at least one year were reviewed. The proportion of patients with at least one clinical relapse within 3–15 months after treatment onset, the proportion of patients with new T2 or gadolinium-enhancing lesions, and the proportion of subjects who achieved no evidence of disease activity (NEDA) status were assessed.

Results

Three hundred sixteen (98 on IFNβ-1a, 218 on DMF) subjects were included. Baseline demographics were comparable between groups except for age, disease duration, and the number of previous treatments being higher and relapse rate in the prior year being lower in the DMF-treated group. The proportion of patients having a clinical relapse (24.5% vs. 9.6%; OR = 3.04; P < 0.001) or a new MRI lesion (28.6% vs. 8.7%; OR = 4.19, P < 0.001) at 15 months were higher on IFNβ-1a. 79.9% of the patients achieved NEDA status at 15 months on DMF (vs. 51.1% for IFNβ-1a; OR = 0.26, P < 0.001). Further adjustment for demographics, disease characteristics, treatment and relapse history, and subgroup analyses confirmed these findings.

Conclusion

DMF was associated with less clinical and radiological disease activity compared to IFNβ-1a.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin. 2011;29(2):207–17.CrossRef Ramagopalan SV, Sadovnick AD. Epidemiology of multiple sclerosis. Neurol Clin. 2011;29(2):207–17.CrossRef
2.
go back to reference Haghikia A, Hohlfeld R, Gold R, Fugger L. Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends Mol Med. 2013;19(5):309–19.CrossRef Haghikia A, Hohlfeld R, Gold R, Fugger L. Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends Mol Med. 2013;19(5):309–19.CrossRef
3.
go back to reference Tremlett HL, Oger J. Interrupted therapy: stopping and switching of the β-interferons prescribed for MS. Neurology. 2003;61(4):551–4.CrossRef Tremlett HL, Oger J. Interrupted therapy: stopping and switching of the β-interferons prescribed for MS. Neurology. 2003;61(4):551–4.CrossRef
4.
go back to reference Paty DW, Li D, Ubc MS/MRI Study Group, IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: II MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993;43(4):662.CrossRef Paty DW, Li D, Ubc MS/MRI Study Group, IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: II MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993;43(4):662.CrossRef
5.
go back to reference O’Connor P, Filippi M, Arnason B, Comi G, Cook S, Goodin D, Hartung HP, Jeffery D, Kappos L, Boateng F, Filippov V. 250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8(10):889–97.CrossRef O’Connor P, Filippi M, Arnason B, Comi G, Cook S, Goodin D, Hartung HP, Jeffery D, Kappos L, Boateng F, Filippov V. 250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8(10):889–97.CrossRef
6.
go back to reference Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39(3):285–94.CrossRef Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Granger CV, Simon JH, Alam JJ. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39(3):285–94.CrossRef
7.
go back to reference Mikol DD, Barkhof F, Chang P, Coyle PK, Jeffery DR, Schwid SR, Stubinski B, Uitdehaag BM, REGARD Study Group. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. The Lancet Neurology. 2008;7(10):903–14.CrossRef Mikol DD, Barkhof F, Chang P, Coyle PK, Jeffery DR, Schwid SR, Stubinski B, Uitdehaag BM, REGARD Study Group. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. The Lancet Neurology. 2008;7(10):903–14.CrossRef
8.
go back to reference Comi G, Filippi M, Wolinsky JS, European/Canadian Glatiramer Acetate Study Group. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol. 2001;49(3):290–7.CrossRef Comi G, Filippi M, Wolinsky JS, European/Canadian Glatiramer Acetate Study Group. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol. 2001;49(3):290–7.CrossRef
9.
go back to reference Ebers GC. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352(9139):1498–504.CrossRef Ebers GC. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352(9139):1498–504.CrossRef
10.
go back to reference Schimrigk S, Brune N, Hellwig K, Lukas C, Bellenberg B, Rieks M, Hoffmann V, Pöhlau D, Przuntek H. Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurol. 2006;13(6):604–10.CrossRef Schimrigk S, Brune N, Hellwig K, Lukas C, Bellenberg B, Rieks M, Hoffmann V, Pöhlau D, Przuntek H. Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurol. 2006;13(6):604–10.CrossRef
11.
go back to reference Fox RJ, Kita M, Cohan SL, Henson LJ, Zambrano J, Scannevin RH, O’Gorman J, Novas M, Dawson KT, Phillips JT. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2014;30(2):251–62.CrossRef Fox RJ, Kita M, Cohan SL, Henson LJ, Zambrano J, Scannevin RH, O’Gorman J, Novas M, Dawson KT, Phillips JT. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2014;30(2):251–62.CrossRef
12.
go back to reference Bomprezzi R. Dimethyl fumarate in the treatment of relapsing–remitting multiple sclerosis: an overview. Ther Adv Neurol Disord. 2015;8(1):20–30.CrossRef Bomprezzi R. Dimethyl fumarate in the treatment of relapsing–remitting multiple sclerosis: an overview. Ther Adv Neurol Disord. 2015;8(1):20–30.CrossRef
13.
go back to reference Kappos L, Gold R, Miller DH, MacManus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 2008;372(9648):1463–72.CrossRef Kappos L, Gold R, Miller DH, MacManus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 2008;372(9648):1463–72.CrossRef
14.
go back to reference Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–107.CrossRef Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–107.CrossRef
15.
go back to reference Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–97.CrossRef Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–97.CrossRef
16.
go back to reference Gauthier SA, Glanz BI, Mandel M, Weiner HL. A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006;5(8):532–6.CrossRef Gauthier SA, Glanz BI, Mandel M, Weiner HL. A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006;5(8):532–6.CrossRef
17.
go back to reference Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444.CrossRef Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444.CrossRef
18.
go back to reference Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.CrossRef Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.CrossRef
19.
go back to reference Tramacere I, Del Giovane C, Salanti G, D'Amico R, Filippini G. Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2015(9). Tramacere I, Del Giovane C, Salanti G, D'Amico R, Filippini G. Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2015(9).
20.
go back to reference Gold R, Arnold DL, Bar-Or A, Hutchinson M, Kappos L, Havrdova E, MacManus DG, Yousry TA, Pozzilli C, Selmaj K, Sweetser MT. Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: interim analysis of ENDORSE, a randomized extension study. Mult Scler J. 2017;23(2):253–65.CrossRef Gold R, Arnold DL, Bar-Or A, Hutchinson M, Kappos L, Havrdova E, MacManus DG, Yousry TA, Pozzilli C, Selmaj K, Sweetser MT. Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: interim analysis of ENDORSE, a randomized extension study. Mult Scler J. 2017;23(2):253–65.CrossRef
21.
go back to reference Tremlett H, Zhao Y, Joseph J, Devonshire V. Relapses in multiple sclerosis are age-and time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–74.CrossRef Tremlett H, Zhao Y, Joseph J, Devonshire V. Relapses in multiple sclerosis are age-and time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–74.CrossRef
22.
go back to reference Benson LA, Healy BC, Gorman MP, Baruch NF, Gholipour T, Musallam A, Chitnis T. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Multiple Scleros Rel Disord. 2014;3(2):186–93.CrossRef Benson LA, Healy BC, Gorman MP, Baruch NF, Gholipour T, Musallam A, Chitnis T. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Multiple Scleros Rel Disord. 2014;3(2):186–93.CrossRef
23.
go back to reference Lorscheider J, Benkert P, Lienert C, Hänni P, Derfuss T, Kuhle J, Kappos L, Yaldizli Ö. Comparative analysis of dimethyl fumarate and fingolimod in relapsing–remitting multiple sclerosis. J Neurol. 2021;268(3):941–9.CrossRef Lorscheider J, Benkert P, Lienert C, Hänni P, Derfuss T, Kuhle J, Kappos L, Yaldizli Ö. Comparative analysis of dimethyl fumarate and fingolimod in relapsing–remitting multiple sclerosis. J Neurol. 2021;268(3):941–9.CrossRef
24.
go back to reference Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRef Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRef
25.
go back to reference D’Amico E, Zanghì A, Romeo M, Cocco E, Maniscalco GT, Brescia Morra V, Paolicelli D, De Luca G, Galgani S, Amato MP, Salemi G. Injectable versus oral first-line disease-modifying therapies: results from the Italian MS Register. Neurotherapeutics. 2021;18(2):905–19.CrossRef D’Amico E, Zanghì A, Romeo M, Cocco E, Maniscalco GT, Brescia Morra V, Paolicelli D, De Luca G, Galgani S, Amato MP, Salemi G. Injectable versus oral first-line disease-modifying therapies: results from the Italian MS Register. Neurotherapeutics. 2021;18(2):905–19.CrossRef
26.
go back to reference Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol. 2021;17(11):676–88.CrossRef Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol. 2021;17(11):676–88.CrossRef
27.
go back to reference Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon β-1a for relapsing multiple sclerosis. Clin Ther. 2007;29(9):2031–48.CrossRef Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon β-1a for relapsing multiple sclerosis. Clin Ther. 2007;29(9):2031–48.CrossRef
28.
go back to reference Panitch H, Goodin DS, Francis GF, Chang P, Coyle PK, O’connor P, Monaghan E, Li D, Weinshenker B. Randomized, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59(10):1496–506.CrossRef Panitch H, Goodin DS, Francis GF, Chang P, Coyle PK, O’connor P, Monaghan E, Li D, Weinshenker B. Randomized, comparative study of interferon β-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59(10):1496–506.CrossRef
29.
go back to reference Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.CrossRef Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.CrossRef
30.
go back to reference Coles A, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012;78(14):1069–78.CrossRef Coles A, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012;78(14):1069–78.CrossRef
31.
go back to reference Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–1801. Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–1801.
32.
go back to reference Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Doan-Do Bass A, Wynn DR, Margolin DH, Lake SL, Moran S. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011;10(4):338–48.CrossRef Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Doan-Do Bass A, Wynn DR, Margolin DH, Lake SL, Moran S. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011;10(4):338–48.CrossRef
33.
go back to reference Calabrese M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Rinaldi F, Perini P, Gallo P. Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing–remitting multiple sclerosis. Mult Scler J. 2012;18(4):418–24.CrossRef Calabrese M, Bernardi V, Atzori M, Mattisi I, Favaretto A, Rinaldi F, Perini P, Gallo P. Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing–remitting multiple sclerosis. Mult Scler J. 2012;18(4):418–24.CrossRef
34.
go back to reference Hartung HP, Aktas O. Evolution of multiple sclerosis treatment: next generation therapies meet next generation efficacy criteria. Lancet Neurol. 2011;10(4):293–5.CrossRef Hartung HP, Aktas O. Evolution of multiple sclerosis treatment: next generation therapies meet next generation efficacy criteria. Lancet Neurol. 2011;10(4):293–5.CrossRef
35.
go back to reference Sormani MP, Li DK, Bruzzi P, Stubinski B, Cornelisse P, Rocak S, De Stefano N. Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis. Neurology. 2011;77(18):1684–90.CrossRef Sormani MP, Li DK, Bruzzi P, Stubinski B, Cornelisse P, Rocak S, De Stefano N. Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis. Neurology. 2011;77(18):1684–90.CrossRef
36.
go back to reference Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC. The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability. Brain. 2010;133(7):1914–29.CrossRef Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC. The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability. Brain. 2010;133(7):1914–29.CrossRef
37.
go back to reference Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015;72(2):152–8.CrossRef Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol. 2015;72(2):152–8.CrossRef
38.
go back to reference Giovannoni G, Gold R, Kappos L, Arnold D, Bar-Or A, Selmaj K, Zhang A, Sheikh S, Dawson K. BG-12 increases the proportion of patients free of clinical and radiologic disease activity in relapsing-remitting multiple sclerosis: findings from the DEFINE study (PD5. 005). 2012. Giovannoni G, Gold R, Kappos L, Arnold D, Bar-Or A, Selmaj K, Zhang A, Sheikh S, Dawson K. BG-12 increases the proportion of patients free of clinical and radiologic disease activity in relapsing-remitting multiple sclerosis: findings from the DEFINE study (PD5. 005). 2012.
Metadata
Title
Comparison of dimethyl fumarate and interferon outcomes in an MS cohort
Authors
Neda Sattarnezhad
Brian C. Healy
Moogeh Baharnoori
Camilo Diaz-Cruz
James Stankiewicz
Howard L. Weiner
Tanuja Chitnis
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-022-02761-8

Other articles of this Issue 1/2022

BMC Neurology 1/2022 Go to the issue