Immunological Aspects of Approved MS Therapeutics

doi:10.3389/fimmu.2019.01564

Review

. 2019 Jul 11:10:1564.

doi: 10.3389/fimmu.2019.01564. eCollection 2019.

Immunological Aspects of Approved MS Therapeutics

Paulus S Rommer¹, Ron Milo^{2

3}, May H Han⁴, Sammita Satyanarayan⁴, Johann Sellner^{5

6}, Larissa Hauer⁷, Zsolt Illes^{8

9}, Clemens Warnke¹⁰, Sarah Laurent¹⁰, Martin S Weber^{11

12}, Yinan Zhang¹³, Olaf Stuve^{6

13

14}

Affiliations

¹ Department of Neurology, Medical University of Vienna, Vienna, Austria.
² Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.
³ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁴ Neuroimmunology Division, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States.
⁵ Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
⁶ Department of Neurology, Klinikum Rechts der Isar, Technische Universität, Munich, Germany.
⁷ Department of Psychiatry, Psychotherapy, and Psychosomatics, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
⁸ Department of Neurology, Odense University Hospital, Odense, Denmark.
⁹ Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹⁰ Department of Neurology, Medical Faculty, University of Köln, Cologne, Germany.
¹¹ Institute of Neuropathology, University Medical Center, Göttingen, Germany.
¹² Department of Neurology, University Medical Center, Göttingen, Germany.
¹³ Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
¹⁴ Neurology Section, VA North Texas Health Care System, Medical Service Dallas, VA Medical Center, Dallas, TX, United States.

PMID: 31354720
PMCID: PMC6637731
DOI: 10.3389/fimmu.2019.01564

Free PMC article

Review

Immunological Aspects of Approved MS Therapeutics

Paulus S Rommer et al. Front Immunol. 2019.

Free PMC article

. 2019 Jul 11:10:1564.

doi: 10.3389/fimmu.2019.01564. eCollection 2019.

Authors

Affiliations

¹ Department of Neurology, Medical University of Vienna, Vienna, Austria.
² Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.
³ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁴ Neuroimmunology Division, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States.
⁵ Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
⁶ Department of Neurology, Klinikum Rechts der Isar, Technische Universität, Munich, Germany.
⁷ Department of Psychiatry, Psychotherapy, and Psychosomatics, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.
⁸ Department of Neurology, Odense University Hospital, Odense, Denmark.
⁹ Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹⁰ Department of Neurology, Medical Faculty, University of Köln, Cologne, Germany.
¹¹ Institute of Neuropathology, University Medical Center, Göttingen, Germany.
¹² Department of Neurology, University Medical Center, Göttingen, Germany.
¹³ Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
¹⁴ Neurology Section, VA North Texas Health Care System, Medical Service Dallas, VA Medical Center, Dallas, TX, United States.

PMID: 31354720
PMCID: PMC6637731
DOI: 10.3389/fimmu.2019.01564

Abstract

Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.

Keywords: immunomodulation; immunosuppression; immunotherapeutics; monoclonal antibodies; multiple sclerosis.

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References

1. Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. (2017) 16:877–97. 10.1016/S1474-4422(17)30299-5 - DOI - PMC - PubMed
1. Fredrikson S, Kam-Hansen S. The 150-year anniversary of multiple sclerosis: does its early history give an etiological clue? Perspect Biol Med. (1989) 32:237–43. 10.1353/pbm.1989.0000 - DOI - PubMed
1. Murray TJ. The history of multiple sclerosis: the changing frame of the disease over the centuries. J Neurol Sci. (2009) 277(Suppl. 1):S3–8. 10.1016/S0022-510X(09)70003-6 - DOI - PubMed
1. Zettl UK, Hecker M, Aktas O, Wagner T, Rommer PS. Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge. Expert Rev Clin Immunol. (2018) 14:137–53. 10.1080/1744666X.2018.1426462 - DOI - PubMed
1. Rommer PS, Zettl UK. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients. Expert Opin Pharmacother. (2018) 19:483–98. 10.1080/14656566.2018.1446944 - DOI - PubMed

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[1] Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. (2017) 16:877–97. 10.1016/S1474-4422(17)30299-5 - DOI - PMC - PubMed

[2] Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. (2017) 16:877–97. 10.1016/S1474-4422(17)30299-5 - DOI - PMC - PubMed

[3] Fredrikson S, Kam-Hansen S. The 150-year anniversary of multiple sclerosis: does its early history give an etiological clue? Perspect Biol Med. (1989) 32:237–43. 10.1353/pbm.1989.0000 - DOI - PubMed

[4] Fredrikson S, Kam-Hansen S. The 150-year anniversary of multiple sclerosis: does its early history give an etiological clue? Perspect Biol Med. (1989) 32:237–43. 10.1353/pbm.1989.0000 - DOI - PubMed

[5] Murray TJ. The history of multiple sclerosis: the changing frame of the disease over the centuries. J Neurol Sci. (2009) 277(Suppl. 1):S3–8. 10.1016/S0022-510X(09)70003-6 - DOI - PubMed

[6] Murray TJ. The history of multiple sclerosis: the changing frame of the disease over the centuries. J Neurol Sci. (2009) 277(Suppl. 1):S3–8. 10.1016/S0022-510X(09)70003-6 - DOI - PubMed

[7] Zettl UK, Hecker M, Aktas O, Wagner T, Rommer PS. Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge. Expert Rev Clin Immunol. (2018) 14:137–53. 10.1080/1744666X.2018.1426462 - DOI - PubMed

[8] Zettl UK, Hecker M, Aktas O, Wagner T, Rommer PS. Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge. Expert Rev Clin Immunol. (2018) 14:137–53. 10.1080/1744666X.2018.1426462 - DOI - PubMed

[9] Rommer PS, Zettl UK. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients. Expert Opin Pharmacother. (2018) 19:483–98. 10.1080/14656566.2018.1446944 - DOI - PubMed

[10] Rommer PS, Zettl UK. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients. Expert Opin Pharmacother. (2018) 19:483–98. 10.1080/14656566.2018.1446944 - DOI - PubMed

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Immunological Aspects of Approved MS Therapeutics

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Immunological Aspects of Approved MS Therapeutics

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