Categories
Multiple sclerosis

How rapidly does ocrelizumab act in relapsing remitting MS?

Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis

Barkhof F, Kappos L, Wolinsky JS, et al.

Neurology 2019 (Epub ahead of print).

Abstract

BACKGROUND:

To assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS).

METHODS:

Brain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-β-1a (44 μg).

RESULTS:

In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-β-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-β-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-β-1a within the first 8 weeks.

CONCLUSION:

Epoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively.

This paper is cited in the neurochecklist:

Ocrelizumab

Abstract link

Axial MRI scans of a person with multiple sclerosis. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/30208218503
Categories
Neurochecklists updates

30 recently revised and updated practical neurology checklists

Neurochecklists is proud of being comprehensive and practical.

But more than that, we take pride in keeping each checklist updated.

To do this, we keep a keen eye on all relevant developments in the literature.

And below are just a few of the checklists that we have recently revised.

They all reflect findings from the latest neurology publications.

***

Anti Ma2 syndrome

Cerebral aneurysms rupture risk factors

Cerebral vein thrombosis

CGRP monoclonal antibodies

CJD

Dural AV fistula management

Giant cell arteritis treatment

Gluten sensitivity neurology

IIH clinical features

King-Denborough syndrome

Levetiracetam

Migraine acute treatment

MND c9orf72

Multiple sclerosis clinical features

Narcolepsy

Normal pressure hydrocephalus

Ocular myasthenia gravis

Oculopharyngeal muscular dystrophy

Ocrelizumab

Parkinson’s disease risk factors

Post stroke recrudescence

PSP variants

Psychogenic seizures

Rapid onset dystonia-parkinsonism

Retinal migraine

Seizure manifestations

Stiff person syndrome

Subacute combined degeneration

Suprascapular neuropathy

Thrombolysis

***

Categories
Multiple sclerosis

The innovative treatments relieving the burden of people with multiple sclerosis

The drug armoury for multiple sclerosis (MS) is ever-expanding. This topic has been extensively covered by our sister blog, The Neurology Lounge, in the blog posts titled:

 Which are the remarkable drugs which have transformed the treatment of MS

Multiple sclerosis treatment: new kids on the block

The emerging progress from the world of MS

How good is ocrelizumab for primary progressive MS

By Marvin 101Own work, CC BY-SA 3.0, Link

This blog post lists all the current MS disease modifying therapies (DMTs), with links to their Neurochecklist page. Each checklist gives a comprehensive summary of mode of action, dosing, side effects, monitoring indices, and precautions. Here they are:

DMTs for mild disease

Interferons

Glatiramer acetate

Terifluonomide

Dimethyl fumarate

By Marvin 101Kazi yangu, CC BY-SA 3.0, Link

DMTs for aggressive disease

Fingolimod

Natalizumab

Alemtuzumab

By Roman H. Khonsari, Vincent Calvez – The Origins of Concentric Demyelination: Self-Organization in the Human Brain. Roman H. Khonsari and Vincent Calvez PLoS ONE. 2007; 2(1): e150. [1], CC BY 1.0, Link

Second line DMTs for aggressive disease

Cladribine

Mitoxantrone

Cyclophosphamide

Haematopoeitic stem cell transplant (HSCT)

By Ryddragyn at English Wikipedia – Transferred from en.wikipedia to Commons., Public Domain, Link


Because the work is never done with MS, we also list the emerging DMTs that will shape MS practice in the near future.

Monoclonal antibodies

Rituximab

Ofatumumab

By Oguenther at de.wikipediaOwn work mit Jmol auf Basis RCSB PDB: 2OSL​., Public Domain, Link

Sphingosin-1-phosphate receptor modulators

Ozanimod

Siponimod

Amiselimod

MD1003 (high dose biotin)

Laquinimod

Ponesimod

Ceralifimod

By Jynto (talk) – Own workThis chemical image was created with Discovery Studio Visualizer., CC0, Link

Phosphodiesterase inhibitors

Ibudilast

Tyrosine 1 kinase inhibitors

Masitinib

 

Boghog自己的作品CC BY-SA 3.0链接
Categories
Multiple sclerosis

How good is ocrelizumab for primary progressive MS?

Ocrelizumab versus placebo in primary progressive multiple sclerosis

Montalban X, Hauser SL, Kappos L, et al; ORATORIO Clinical Investigators.

N Engl J Med 2016; doi: 10.1056/NEJMoa1606468 (Epub ahead of print).

Abstract

BACKGROUND:

An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease.

METHODS:

In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis.

RESULTS:

The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.

CONCLUSIONS:

Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab.

You may also check out:

The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects.

Sorensen PS, Blinkenberg M.

Ther Adv Neurol Disord 2016; 9:44-52.

Both references are now included in the neurochecklist:

Multiple sclerosis (MS): emerging treatments

screen-shot-2016-12-24-at-23-32-53

Abstract link 1

Abstract link 2

B0007277 Monoclonal antibodies. Wellcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814713820
B0007277 Monoclonal antibodies. Wellcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814713820