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Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review.
Neurol Ther. 2020 Jun; 9(1):55-66.NT

Abstract

The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era.

Authors+Show Affiliations

Department of Clinical Neurosciences, Salmaniya Medical Complex, PO Box 12, Manama, Bahrain. isasharoqi2@hotmail.com.King Fahad Medical City, Ministry of Health, Riyadh, Kingdom of Saudi Arabia.Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.Department of Neurology, Karadeniz Technical University, Trabzon, Turkey.King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia.Hopital Libanais Geitaoui, Beirut, Lebanon.Neurology Department, Rashid Hospital and Dubai Medical College, Dubai Health Authority, Dubai, United Arab Emirates.Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088, Berlin, Germany.Life Wilgers Hospital, Pretoria, South Africa.MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.Department of Neurology, Sheikh Khalifa Ibn Zaid Hospital, Mohammed VI University, Casablanca, Morocco.Merck, Dubai, United Arab Emirates.Faculty of Medicine, Ain Shams University, Cairo, Egypt.Danish Multiple Sclerosis Center, University of Copenhagen-Rigshospitalet, Copenhagen, Denmark.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32297127

Citation

AlSharoqi, Isa Ahmed, et al. "Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? a Narrative Review." Neurology and Therapy, vol. 9, no. 1, 2020, pp. 55-66.
AlSharoqi IA, Aljumah M, Bohlega S, et al. Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review. Neurol Ther. 2020;9(1):55-66.
AlSharoqi, I. A., Aljumah, M., Bohlega, S., Boz, C., Daif, A., El-Koussa, S., Inshasi, J., Kurtuncu, M., Müller, T., Retief, C., Sahraian, M. A., Shaygannejad, V., Slassi, I., Taha, K., Zakaria, M., & Sørensen, P. S. (2020). Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review. Neurology and Therapy, 9(1), 55-66. https://doi.org/10.1007/s40120-020-00187-3
AlSharoqi IA, et al. Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? a Narrative Review. Neurol Ther. 2020;9(1):55-66. PubMed PMID: 32297127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review. AU - AlSharoqi,Isa Ahmed, AU - Aljumah,Mohamed, AU - Bohlega,Saeed, AU - Boz,Cavit, AU - Daif,Abdelkader, AU - El-Koussa,Salam, AU - Inshasi,Jihad, AU - Kurtuncu,Murat, AU - Müller,Thomas, AU - Retief,Chris, AU - Sahraian,Mohammad Ali, AU - Shaygannejad,Vahid, AU - Slassi,Ilham, AU - Taha,Karim, AU - Zakaria,Magd, AU - Sørensen,Per Soelberg, Y1 - 2020/04/15/ PY - 2020/03/17/received PY - 2020/4/17/pubmed PY - 2020/4/17/medline PY - 2020/4/17/entrez KW - Disease-modifying drug KW - Escalation therapy KW - Immune reconstitution therapy KW - Maintenance therapy KW - Multiple sclerosis SP - 55 EP - 66 JF - Neurology and therapy JO - Neurol Ther VL - 9 IS - 1 N2 - The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era. SN - 2193-8253 UR - https://www.unboundmedicine.com/medline/citation/32297127/Immune_Reconstitution_Therapy_or_Continuous_Immunosuppression_for_the_Management_of_Active_Relapsing-Remitting_Multiple_Sclerosis_Patients_A_Narrative_Review L2 - https://dx.doi.org/10.1007/s40120-020-00187-3 DB - PRIME DP - Unbound Medicine ER -
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