Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing–Remitting Multiple Sclerosis Patients? A Narrative Review

Ia, AlSharoqi; Al-Jumah, Mohammad; Bohlega, Saeed; Boz, Cavit; Daif, Abdulkader; El-Koussa, S; Inshasi, Jihad; Kürtüncü, Murat; Müller, Thomas; Retief, C.P.; Sahraian, Mohammad Ali; Shaygannejad,; Slassi, I.; Taha, Karim; Zakaria, Magd; Ps, Sørensen

doi:10.1007/s40120-020-00187-3

Cited by 22 publications

(35 citation statements)

References 63 publications

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“…Fingolimod belongs to a class of drugs that targets the sphingolipid-regulated signaling system, acting as a functional antagonist of the sphingosine-1-phosphate type 1 (S1P1) receptor immunomodulatory [1], although some authors consider it to be an immunosuppressant [2]. It is a prodrug that is phosphorylated by sphingosine kinases to its active form, phosphofingolimod [1].…”

Section: Introductionmentioning

confidence: 99%

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

et al. 2020

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Background Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). Objectives To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. Methods Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. Results Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. Conclusions Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.

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Section: Introductionmentioning

confidence: 99%

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

et al. 2020

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“…Chronic immunosuppression and immunomodulation are the most commonly used therapeutic strategies for MS, outside of symptom management. In addition to traditional disease-modifying therapies, immune reconstitution therapy (IRT) has emerged as a novel treatment paradigm (AlSharoqi et al, 2020;Derfuss et al, 2020). The latter is based on partial or full ablation of the immune system aiming to destroy self-reactive clones and restore normal function.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Pre-clinical and Clinical Implications of “Inside-Out” vs. “Outside-In” Paradigms in Multiple Sclerosis Etiopathogenesis

Titus

Chen

Podojil

et al. 2020

Front. Cell. Neurosci.

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Multiple Sclerosis (MS) is an immune-mediated neurological disorder, characterized by central nervous system (CNS) inflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Although autoimmunity, inflammatory demyelination and neurodegeneration underlie MS, the initiating event has yet to be clarified. Effective disease modifying therapies need to both regulate the immune system and promote restoration of neuronal function, including remyelination. The challenge in developing an effective long-lived therapy for MS requires that three disease-associated targets be addressed: (1) self-tolerance must be re-established to specifically inhibit the underlying myelin-directed autoimmune pathogenic mechanisms; (2) neurons must be protected from inflammatory injury and degeneration; (3) myelin repair must be engendered by stimulating oligodendrocyte progenitors to remyelinate CNS neuronal axons. The combined use of chronic and relapsing remitting experimental autoimmune encephalomyelitis (C-EAE, R-EAE) ("outside-in") as well as progressive diphtheria toxin A chain (DTA) and cuprizone autoimmune encephalitis (CAE) ("inside-out") mouse models allow for the investigation and specific targeting of all three of these MSassociated disease parameters. The "outside-in" EAE models initiated by myelin-specific autoreactive CD4 + T cells allow for the evaluation of both myelin-specific tolerance in the absence or presence of neuroprotective and/or remyelinating agents. The "inside-out" mouse models of secondary inflammatory demyelination are triggered by toxin-induced oligodendrocyte loss or subtle myelin damage, which allows evaluation of novel therapeutics that could promote remyelination and neuroprotection in the CNS. Overall, utilizing these complementary pre-clinical MS models will open new avenues for developing therapeutic interventions, tackling MS from the "outside-in" and/or "inside-out".

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“…Intensive monitoring requirements or the need to visit hospitals for infusions of some DMTs adds to the burden of treatment with some DMTs [ 78 ]. The IRT approach renders these issues moot [ 18 , 36 , 79 , 80 ]: for example, for a patient who responds to treatment with cladribine tablets there is no need for regular intakes of treatment or for continued monitoring beyond 6 months of the last dose (or the recovery of lymphocytes, if this takes longer). This expert group supported this principle, as their support for the use of cladribine tablets in CLARITY-like patients (one relapse in the previous year or 2 relapses in the previous 2 years) was stronger if the patient’s lifestyle preferences mitigated against the use of continuous treatment or if the patient was likely to be non-compliant with this approach.…”

Section: Discussionmentioning

confidence: 99%

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates

Inshasi

Al-Fahad²,

Alsaadi³

et al. 2021

Neurol Ther

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The use of immune reconstitution therapies (IRT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a prolonged period of freedom from relapses in the absence of continuously applied therapy. Cladribine tablets is a disease-modifying treatment (DMT) indicated for highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features. Treatment with cladribine tablets is effective and well tolerated in patients with active MS disease and have a low burden of monitoring during and following treatment. In this article, an expert group of specialist neurologists involved in the care of patients with MS in the United Arab Emirates provides their consensus recommendations for

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Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing–Remitting Multiple Sclerosis Patients? A Narrative Review

Cited by 22 publications

References 63 publications

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

Pre-clinical and Clinical Implications of “Inside-Out” vs. “Outside-In” Paradigms in Multiple Sclerosis Etiopathogenesis

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates

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