4.5 Review

Efficacy and Safety of Multiple Sclerosis Drugs Approved Since 2018 and Future Developments

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Article Immunology

Humoral and cellular immunity in convalescent COVID-19 people with multiple sclerosis treated with ofatumumab

Ivan Adamec et al.

Summary: This study reports the clinical outcomes and immune development in convalescent COVID-19 patients with multiple sclerosis (pwMS) treated with ofatumumab. The study found that while no antibody response was observed in pwMS treated with ofatumumab, all patients showed T cell immunity against SARS-CoV-2.

JOURNAL OF NEUROIMMUNOLOGY (2022)

Article Clinical Neurology

Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials

Gavin Giovannoni et al.

Summary: The study demonstrates that patients who initiate OCR treatment earlier have a reduced risk of requiring a walking aid, highlighting the long-term implications of early highly effective treatment.

EUROPEAN JOURNAL OF NEUROLOGY (2022)

Article Medicine, Research & Experimental

Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study

Sibyl Wray et al.

Summary: This study evaluated the safety and gastrointestinal tolerability of switching to Diroximel fumarate (DRF) from other disease-modifying therapies (DMTs) in patients with relapsing multiple sclerosis. The results showed consistent safety outcomes with previous studies and suggested that the transition to DRF is a reasonable treatment strategy with low rates of discontinuation due to gastrointestinal adverse events.

ADVANCES IN THERAPY (2022)

Article Clinical Neurology

Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

Ralf Gold et al.

Summary: This study assessed the long-term safety and efficacy of dimethyl fumarate (DMF) in multiple sclerosis patients for up to 13 years. The results demonstrate sustained safety and efficacy of DMF treatment, with low annualized relapse rates and a majority of patients showing no disability worsening over the long-term treatment period. This supports the positive benefit-risk profile of DMF for long-term RRMS treatment.

MULTIPLE SCLEROSIS JOURNAL (2022)

Article Clinical Neurology

S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal

Vasileios-Periklis Stamatellos et al.

Summary: This study found that S1P receptor modulators may increase the reporting risk of skin cancer, especially basal cell carcinoma, based on adverse event reports from FAERS.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2022)

Article Clinical Neurology

Long-term Treatment With Ponesimod in Relapsing-Remitting Multiple Sclerosis Results From Randomized Phase 2b Core and Extension Studies

Mark S. Freedman et al.

Summary: This study evaluated the dose-response relationship and long-term efficacy and safety of ponesimod in patients with relapsing-remitting multiple sclerosis. The results showed that a dose of 20 mg ponesimod maintained disease control for approximately 8 years with no new safety concerns.

NEUROLOGY (2022)

Article Clinical Neurology

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

Edward Fox et al.

Summary: The study demonstrated that Ublituximab is safe and effective in relapsing multiple sclerosis patients, leading to rapid depletion of B-cells and significant reductions in MRI activity and relapses.

MULTIPLE SCLEROSIS JOURNAL (2021)

Article Clinical Neurology

Siponimod and Cognition in Secondary Progressive Multiple Sclerosis EXPAND Secondary Analyses

Ralph H. B. Benedict et al.

Summary: The study shows that siponimod has a significant benefit on cognitive processing speed in patients with secondary progressive multiple sclerosis. Siponimod-treated patients were at significantly lower risk for a >= 4-point decrease in SDMT score and had a significantly higher chance for a >= 4-point increase, which is considered clinically meaningful.

NEUROLOGY (2021)

Article Clinical Neurology

Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis

Steve Simpson-Yap et al.

Summary: Using data from 12 sources in 28 countries, this study examined the characteristics of COVID-19 severity in people with MS, particularly those taking immunosuppressive therapies. The results showed that older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Additionally, rituximab was consistently associated with increased risk of hospitalization, ICU admission, and need for ventilation, while ocrelizumab was mainly associated with hospitalization and ICU admission.

NEUROLOGY (2021)

Review Cell Biology

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

H. Yesid Estupinan et al.

Summary: BTK inhibitors have shown efficacy in treating B-cell tumors, but are increasingly being tested for autoimmune diseases and inflammation. Adverse effects such as cardiovascular issues and bleeding can persist, while skin manifestations and diarrhea may occur early but subside.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Review Clinical Neurology

Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis

Reshmi Roy et al.

Summary: Fingolimod was the first-in-class S1P receptor modulator approved for the treatment of relapsing forms of MS, aiming to modulate immune cell trafficking and reduce infiltration into the central nervous system. Second-generation S1PR modulators have improved selectivity and shorter half-lives, allowing for faster reversal of pharmacological effects and minimizing cardiac-related side effects.

CNS DRUGS (2021)

Article Clinical Neurology

Pharmacokinetics and Bioavailability of Monomethyl Fumarate Following a Single Oral Dose of Bafiertam™ (Monomethyl Fumarate) or Tecfidera(R) (Dimethyl Fumarate)

Thomas W. Lategan et al.

Summary: The study confirmed the bioequivalence between two Bafiertam(TM) capsules and one Tecfidera(R) capsule, both of which were found to be safe and generally well tolerated.

CNS DRUGS (2021)

Article Clinical Neurology

Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study A Randomized Clinical Trial

Ludwig Kappos et al.

Summary: In the OPTIMUM trial, ponesimod showed superiority over teriflunomide in reducing annualized relapse rate, fatigue, MRI activity, brain volume loss, and NEDA status, but not in confirmed disability accumulation. The safety profile was consistent with previous observations and known S1P receptor modulators.

JAMA NEUROLOGY (2021)

Letter Clinical Neurology

Development of SARS-CoV-2 IgM and IgG antibodies in a relapsing multiple sclerosis patient on ofatumumab

Ramon E. Flores-Gonzalez et al.

Summary: This case study suggests that MS patients treated with ofatumumab are able to produce effective antiviral antibodies in response to SARS-CoV-2 infection, with sustained levels of IgG antibodies. Further research is needed to evaluate the humoral response of MS patients on ofatumumab to SARS-CoV-2 infection and COVID-19 vaccines.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2021)

Letter Clinical Neurology

Blunted vaccines responses after ocrelizumab highlight need for immunizations prior to treatment

I. Smets et al.

MULTIPLE SCLEROSIS AND RELATED DISORDERS (2021)

Article Clinical Neurology

Plasma neurofilament light chain concentrations as a biomarker of clinical and radiologic outcomes in relapsing multiple sclerosis: Post hoc analysis of Phase 3 ozanimod trials

Sarah Harris et al.

Summary: This study investigated plasma neurofilament light chain concentration (pNfL) as a biomarker for neuroaxonal damage and disease activity in relapsing multiple sclerosis (RMS). Results showed that pNfL was associated with clinical and radiologic measures of disease and treatment effects in RMS, supporting its use as a biomarker. Ozanimod treatment led to greater reduction in pNfL compared to interferon beta-1a, with decreased inflammatory activity and improved disease outcomes.

EUROPEAN JOURNAL OF NEUROLOGY (2021)

Article Clinical Neurology

Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial

Daniel S. Reich et al.

Summary: Tolebrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, showed a dose-dependent reduction in new gadolinium-enhancing lesions in patients with relapsing multiple sclerosis. The 60 mg dose was the most efficacious and well tolerated among the tested doses. These findings provide a scientific rationale to pursue phase 3 clinical trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis.

LANCET NEUROLOGY (2021)

Article Biochemistry & Molecular Biology

Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Sokratis A. Apostolidis et al.

Summary: Patients with multiple sclerosis on anti-CD20 monotherapy exhibit significantly reduced SARS-CoV-2-specific antibodies and memory B cells, while CD4(+) and CD8(+) T cells are robustly activated compared to healthy controls after receiving BNT162b2 or mRNA-1273 mRNA vaccination.

NATURE MEDICINE (2021)

Article Clinical Neurology

Improved gastrointestinal profile with diroximel fumarate is associated with a positive impact on quality of life compared with dimethyl fumarate: results from the randomized, double-blind, phase III EVOLVE-MS-2 study

Annette Wundes et al.

Summary: This study demonstrated that compared to DMF, DRF has better GI tolerability, with patients experiencing less impact on daily life and work, and requiring less concomitant symptomatic medication use.

THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS (2021)

Article Clinical Neurology

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Anat Achiron et al.

Summary: The study found that after receiving the COVID-19 vaccine, MS patients who were either untreated or treated with cladribine showed a high level of protective humoral immunity, similar to healthy subjects. However, only a small percentage of MS patients treated with ocrelizumab and fingolimod developed a humoral immune response.

THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS (2021)

Article Medicine, General & Internal

Ofatumumab versus Teriflunomide in Multiple Sclerosis

Stephen L. Hauser et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Review Pharmacology & Pharmacy

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review

Huah Shin Ng et al.

EXPERT OPINION ON DRUG SAFETY (2020)

Article Medicine, General & Internal

Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis

Xavier Montalban et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Article Medicine, Research & Experimental

Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes

Laura Kahari et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

Review Biotechnology & Applied Microbiology

Progressive multiple sclerosis: from pathophysiology to therapeutic strategies

Simon Faissner et al.

NATURE REVIEWS DRUG DISCOVERY (2019)

Article Medicine, General & Internal

Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

J. William L. Brown et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

Review Clinical Neurology

Progressive multiple sclerosis: latest therapeutic developments and future directions

Simon Faissner et al.

THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS (2019)

Article Clinical Neurology

The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination

Abdelkrim Mannioui et al.

MULTIPLE SCLEROSIS JOURNAL (2018)

Article Clinical Neurology

The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination

Abdelkrim Mannioui et al.

MULTIPLE SCLEROSIS JOURNAL (2018)

Review Clinical Neurology

Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010

Simon Faissner et al.

CNS DRUGS (2018)

Article Pharmacology & Pharmacy

Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study

Jonathan Q. Tran et al.

CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT (2018)

Article Medicine, General & Internal

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

S. L. Hauser et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Medicine, General & Internal

Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

X. Montalban et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Immunology

Siponimod (BAF312) prevents synaptic neurodegeneration in experimental multiple sclerosis

Antonietta Gentile et al.

JOURNAL OF NEUROINFLAMMATION (2016)

Article Immunology

The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures

Catherine O'Sullivan et al.

JOURNAL OF NEUROINFLAMMATION (2016)

Review Clinical Neurology

Tumefactive multiple sclerosis lesions in two patients after cessation of fingolimod treatment

Simon Faissner et al.

THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS (2015)

Article Clinical Neurology

Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial

Tomas Olsson et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2014)

Article Chemistry, Medicinal

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator

Shifeng Pan et al.

ACS MEDICINAL CHEMISTRY LETTERS (2013)

Article Medicine, General & Internal

B-cell depletion with Rituximab in relapsing-remitting multiple sclerosis

Stephen L. Hauser et al.

NEW ENGLAND JOURNAL OF MEDICINE (2008)

Article Biochemistry & Molecular Biology

Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate

MG Sanna et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)