P61 Sustained reduction in confirmed disability progression in patients with primary progressive multiple sclerosis treated with ocrelizumab in the open-label extension period of the Phase III ORATORIO trial

Background: Upper extremity (UE) impairment is common with primary progressive multiple sclerosis (PPMS). Objective: This exploratory analysis examined the effects of ocrelizumab on confirmed progression (CP) and confirmed improvement (CI) in UE impairment in patients from ORATORIO. Methods: Patients with PPMS received ocrelizumab 600 mg or placebo every 24 weeks for ⩾120 weeks. The Nine-Hole Peg Test (9HPT) was administered at baseline (BL) and every 12 weeks thereafter. Prespecified exploratory endpoints included change in 9HPT time and proportion of patients with CP of ⩾20% in 9HPT. Analysis populations included intention-to-treat (ITT) patients and subgroups stratified by BL 9HPT time and Expanded Disability Status Scale. Post hoc analyses included the proportion of patients achieving more severe thresholds of CP and the proportion achieving CI in 9HPT. Results: Among ITT patients, ocrelizumab significantly reduced the change in 9HPT time over 120 weeks, the risk of CP of ⩾20% in 9HPT time for both hands and the risk of more severe 9HPT progression versus placebo. Numerical trends also favoured ocrelizumab versus placebo with respect to achieving CI. Consistent directional trends were observed in subgroup analyses. Conclusion: Ocrelizumab reduces the risk of UE disability progression and may increase the possibility of improvement versus placebo in PPMS.

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Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519900971 ◽

2020 ◽

Vol 27 (1) ◽

pp. 28-38 ◽

Cited By ~ 1

Author(s):

Rosa Cortese ◽

Carmen Tur ◽

Ferran Prados ◽

Torben Schneider ◽

Baris Kanber ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Brain Mri ◽

Progressive Multiple Sclerosis ◽

Cervical Cord ◽

Primary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Mixed Effect ◽

Primary Progressive ◽

Over Time

Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. Conclusion: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.

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028 Treating progressive multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.27 ◽

2018 ◽

Vol 89 (6) ◽

pp. A12.1-A12

Author(s):

Jordana Hughes ◽

Vilija Jokubaitis ◽

Mark Slee ◽

Jeannette Lechner-Scott ◽

Anneke Van der Walt ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Disease ◽

Progressive Multiple Sclerosis ◽

Hazard Ratio ◽

Primary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Primary Progressive ◽

Effect Of Therapy ◽

Multivariable Regression ◽

Multivariable Regression Models

IntroductionWe showed that the available immunotherapies do not modify disability outcomes when used in secondary progressive multiple sclerosis. However, these therapies are effective in advanced active multiple sclerosis. Primary progressive multiple sclerosis may present with or without superimposed relapses. Significance of these relapses for disability accumulation and treatment remains contested. We aimed to examine the effect of the available immunotherapies in primary progressive multiple sclerosis.Methods1427 eligible patients with primary progressive multiple sclerosis from MSBase were studied. Confirmed disability progression of disability was compared between treated and untreated propensity score-matched cohorts. Multivariable regression models were used to compare disability accrual between primary progressive multiple sclerosis with and without superimposed relapses. Finally, the effect of therapy on disability accrual in cohorts with and without superimposed relapses was analysed.Results173 treated and 373 untreated patients were matched. No differences in the risk of disability progression (p=0.79) and improvement (p=0.98) were observed over the median 3 year follow-up.The likelihood of disability progression was relatively lower in patients with superimposed relapses (hazard ratio=0.83, p<0.01). We observed an association between the proportion of time on immunotherapy and the hazard of disability progression in active (hazard ratio=0.96, p=0.01) but not in the inactive primary progressive disease (p=0.21).ConclusionSuperimposed relapses in primary progressive multiple sclerosis represent a favourable prognostic marker, associated with slower disability accrual. This is most likely attributed to the effectiveness of immunotherapy in active primary progressive disease. Relapse activity, therefore, is a treatable modifier of disability accrual in primary progressive disease.

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Evaluation of the times of disability progression and related factors in patients with primary progressive multiple sclerosis from Argentina

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2021.103483 ◽

2022 ◽

pp. 103483

Author(s):

Ricardo Alonso ◽

Orlando Garcea ◽

Juan Ignacio Rojas ◽

Marina Alonso ◽

Luciana Lázaro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Primary Progressive Multiple Sclerosis ◽

Disability Progression ◽

Related Factors ◽

Primary Progressive ◽

The Times

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Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis

Annals of Pharmacotherapy ◽

10.1177/1060028017747635 ◽

2017 ◽

Vol 52 (5) ◽

pp. 473-483 ◽

Cited By ~ 6

Author(s):

Amanda M. Stahnke ◽

Kathryn M. Holt

Keyword(s):

Multiple Sclerosis ◽

B Cell ◽

English Language ◽

Data Extraction ◽

Progressive Multiple Sclerosis ◽

Phase Iii ◽

Primary Progressive Multiple Sclerosis ◽

Two Phase ◽

Primary Progressive ◽

Relapsing Remitting

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of ocrelizumab, a new B-cell–targeted therapy for multiple sclerosis (MS). Data Sources: A comprehensive search of PubMed and OVID/MEDLINE was conducted using search terms ocrelizumab and multiple sclerosis using the date range of 1946 through October 2017. Study Selection and Data Extraction: All English-language, human-subject articles related to ocrelizumab and MS were evaluated. Data Synthesis: Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS (PPMS). A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate ( P < 0.001 pooled), disability progression at 12 weeks ( P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P < 0.001). Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P < 0.001). As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection. Conclusions: Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

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