Ocrelizumab therapy and long-term outcomes in multiple sclerosis: clinical and MRI-efficacyand safety profile

Long Term Outcomes ◽

Pooled Data ◽

Delayed Initiation ◽

Anti Cd20

Ocrelizumab (Ocrevus®) is a humanized anti-CD20 monoclonal antibody approved for the treatment of adults with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS). The article presents data on the clinical and MRI efficacy and safety profile of ocrelizumab for the long-term use in patients with MS of various forms of the course. The authors performed the search, systematization and analysis of the pooled data of clinical studies and real clinical practice. Five-year follow-upof ocrelizumab therapy showed a compelling and clinical ly significant advantage in reducing the disease progression in patients with PPMS. After five-year ocrelizumab therapy in patients with PPMS, the study showed a reduction of the proportion of patients with disease progression and degree of brain atrophy, and more frequent achievement of the disease inactivity status (NEDA) as compared to patients with two- year delayed initiation of ocrelizumab therapy. The safety profile of the drug corresponds to the results obtained in the controlled periods of clinical trials.

Cervical Cord Atrophy and Long-Term Disease Progression in Patients with Primary-Progressive Multiple Sclerosis

American Journal of Neuroradiology ◽

10.3174/ajnr.a5495 ◽

2017 ◽

Vol 39 (2) ◽

pp. 399-404 ◽

Cited By ~ 11

Author(s):

F.X. Aymerich ◽

C. Auger ◽

J. Alonso ◽

M. Alberich ◽

J. Sastre-Garriga ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Progression ◽

Cervical Cord ◽

Primary Progressive

Societal costs of primary progressive multiple sclerosis in Australia and the economic impact of a hypothetical disease-modifying treatment that could delay disease progression

Journal of Medical Economics ◽

10.1080/13696998.2021.1872585 ◽

2021 ◽

Vol 24 (1) ◽

pp. 140-149

Author(s):

Laurie J. Brown ◽

Jinjing Li ◽

Matthias Brunner ◽

Martin Snoke ◽

Hai A. La

Keyword(s):

Multiple Sclerosis ◽

Economic Impact ◽

Disease Progression ◽

Societal Costs ◽

Primary Progressive ◽

Delay Disease Progression ◽

Disease Modifying ◽

Disease Modifying Treatment

Primary progressive multiple sclerosis to be treated with ocrelizumab: a mistaken case of cobalamin deficiency

BMJ Case Reports ◽

10.1136/bcr-2018-229080 ◽

2019 ◽

Vol 12 (5) ◽

pp. e229080 ◽

Cited By ~ 1

Author(s):

Sydney Feldman ◽

Salman Aljarallah ◽

Shiv Saidha

Keyword(s):

Multiple Sclerosis ◽

Neurological Disorders ◽

Cobalamin Deficiency ◽

Vitamin B ◽

Primary Progressive ◽

Anti Cd20 ◽

Mri Changes ◽

Spine Mri

Cobalamin (vitamin B12) deficiency often manifests with neurologic symptoms and may rarely mimic multiple sclerosis (MS) among other neurological disorders. However, MRI changes associated with cobalamin deficiency are typically spinal predominant and distinct from MS-related changes. We report a case of a patient with cobalamin deficiency who was recommended by her primary neurologist to commence treatment with ocrelizumab, a potent anti-CD20 B-cell depleting monoclonal antibody, after being diagnosed with primary progressive MS. However, cervical spine MRI demonstrated changes classical of cobalamin deficiency including ‘inverted V sign’ signal hyperintensity and following parenteral cobalamin supplementation her neurological symptoms quickly and dramatically improved.

Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

Scientific Reports ◽

10.1038/s41598-020-72654-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mario Amatruda ◽

Maria Petracca ◽

Maureen Wentling ◽

Benjamin Inbar ◽

Kamilah Castro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Progression ◽

Disease Course ◽

Primary Progressive ◽

T2 Lesions ◽

Relapsing Remitting ◽

One Year ◽

Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000012700 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012700

Author(s):

Stephen L Hauser ◽

Ludwig Kappos ◽

Xavier Montalban ◽

Licinio Craveiro ◽

Cathy Chognot ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trials ◽

Real World ◽

Safety Profile ◽

Continuous Treatment ◽

Class Iii ◽

Primary Progressive ◽

Controlled Treatment

ObjectiveTo report safety of ocrelizumab (OCR) up to 7 years in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) enrolled in clinical trials or treated in real-world postmarketing settings.MethodsSafety analyses are based on integrated clinical and laboratory data for all patients who received OCR in 11 clinical trials, including the controlled treatment and open-label extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional postmarketing data were used. Incidence rates of serious infections (SIs) and malignancies were contextualized using multiple epidemiologic sources.ResultsAt data cut-off (January 2020), 5,680 patients with multiple sclerosis (MS) received OCR (18,218 patient years [PY] of exposure) in clinical trials. Rates per 100 PY (95% CI) of AEs (248; 246–251), serious AEs (7.3; 7.0–7.7), infusion-related reactions (25.9; 25.1–26.6), and infections (76.2; 74.9–77.4) were similar to those within the controlled treatment period of the phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 1.81–2.23) and malignancies (0.46; 0.37–0.57), were consistent with the ranges reported in epidemiologic data.ConclusionContinuous administration of OCR for up to 7 years in clinical trials, as well as its broader use for more than 3 years in the real-world setting, are associated with a favorable and manageable safety profile, without emerging safety concerns in a heterogeneous MS population.Classification of evidenceThis analysis provides Class III evidence that long-term, continuous treatment with OCR has a consistent and favorable safety profile in patients with RMS and PPMS. This study is rated Class III because of the use of OLE data and historical controls.

Secondary Progressive Multiple Sclerosis: New Insights

Neurology ◽

10.1212/wnl.0000000000012323 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012323

Author(s):

Bruce Anthony Campbell Cree ◽

Douglas L Arnold ◽

Jeremy Chataway ◽

Tanuja Chitnis ◽

Robert J. Fox ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Disease ◽

Secondary Progressive Multiple Sclerosis ◽

Response To Treatment ◽

Disability Progression ◽

Long Term Outcomes ◽

Secondary Progressive ◽

Relapsing Remitting

In most cases, multiple sclerosis (MS) begins with a relapsing–remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and is termed secondary progressive multiple sclerosis (SMPS). Major differences exist between relapsing–remitting MS (RRMS) and SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, and challenges in the diagnosis and treatment of SPMS. We emphasize the criticality of conversion from a relapsing–remitting to a secondary progressive disease course not only because such conversion is evidence of disability progression, but also because, until recently, treatments that effectively reduced disability progression in relapsing MS were not proven to be effective in SPMS. Clear clinical, imaging, immunological, or pathological criteria marking the transition from RRMS to SPMS have not yet been established. Early identification of SPMS will require tools which, together with the use of appropriate treatments, may result in better long-term outcomes for the population of patients with SPMS.