scholarly journals Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial

2018 ◽  
Vol 24 (14) ◽  
pp. 1862-1870 ◽  
Author(s):  
Edward J Fox ◽  
Clyde Markowitz ◽  
Angela Applebee ◽  
Xavier Montalban ◽  
Jerry S Wolinsky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Upper Extremity ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Intention To Treat ◽  
Disability Status ◽  
Upper Extremity Impairment ◽  
Post Hoc

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.

Urinary neopterin and nitric oxide metabolites as markers of interferon β-1a activity in primary progressive multiple sclerosis

2010 ◽  
Vol 16 (9) ◽  
pp. 1066-1072 ◽  
Author(s):  
K. Rejdak ◽  
SM Leary ◽  
A. Petzold ◽  
AJ Thompson ◽  
DH Miller ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Interferon Β ◽  
Primary Progressive ◽  
Significant Difference ◽  
Disability Status ◽  
Urinary Neopterin ◽  
Nitric Oxide Metabolites

Background: Interferon beta has not been demonstrated to be effective in exploratory phase 2 clinical trials in primary progressive multiple sclerosis. However, using more sensitive indicators of a treatment response, such as biomarkers, might help to identify sub-groups of patients who may benefit from therapy. Objective: To assess the utility of measuring urinary neopterin and nitric oxide metabolite excretion for monitoring interferon β-1a (IFNβ-1a) treatment in patients with primary progressive multiple sclerosis. Methods: Fifty patients from a phase II trial of IFNβ-1a (Placebo n = 20; Avonex® 1 × 30 μg/week (IFN-30), n = 15; Avonex® 1 × 60 μg/week (IFN-60), n = 15), were enrolled. Patients were assessed using the Expanded Disability Status Scale. Urine samples were collected on each visit, 3 months apart, for a period of 24 months. Nitric oxide metabolites, nitrite/nitrate (NOx), were measured by colorimetric assay and neopterin and creatinine (Cr) were assayed using a high-performance liquid chromatography technique. NOx/creatinine ratio (NOxCR) and urinary neopterin/creatinine ratio (UNCR) quotients were calculated. Results: There was no significant difference between pre-dose, baseline levels of UNCR or NOxCR between the study groups. On the intention-to-treat analysis, there was a significant difference in UNCR levels between the placebo compared with IFN-30 ( p = 0.03) or IFN-60 ( p = 0.002) groups. The IFN-30 and IFN-60 groups did not differ. Within IFNβ-1a-treated patients with primary progressive multiple sclerosis, median UNCR values were significantly higher in clinically stable (no Expanded Disability Status Scale change) compared with progressive patients ( p = 0.002). IFNβ-1a treatment did not significantly influence NOx excretion in patients with primary progressive multiple sclerosis. Conclusions: Urinary neopterin is a potential biomarker to monitor the in vivo effects of IFNβ-1a in primary progressive multiple sclerosis and other multiple sclerosis sub-types.

Differences in the progression of primary progressive multiple sclerosis in Brazilians of African descent versus white Brazilian patients

2010 ◽  
Vol 16 (5) ◽  
pp. 597-603 ◽  
Author(s):  
Claudia Cristina Ferreira Vasconcelos ◽  
Luiz Claudio Santos Thuler ◽  
Gutemberg Augusto Cruz dos Santos ◽  
Marcos Papais Alvarenga ◽  
Marina Papais Alvarenga ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
African Descent ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Primary Progressive ◽  
Kaplan Meier ◽  
Disability Status ◽  
Multiple Sclerosis Patients ◽  
White Patients

Recent studies have suggested faster clinical progression and greater disability in multiple sclerosis patients of African descent. This study analysed the effect of ethnicity on progression and disability. Sixty-five patients with primary progressive multiple sclerosis were selected and classified as being of African descent or white. Time from onset of the disease until reaching Expanded Disability Status Scale grades 3, 6, and 8 was assessed, as well as irreversible disability (Expanded Disability Status Scale grade maintained for ≥6 months). In the African descent group, the median time to reach Expanded Disability Status Scale 3 was 1 year shorter (1 year vs 2 years, p= 0.02), and to reach Expanded Disability Status Scale 6 was 2 years shorter (3 years vs 5 years, p= 0.01) than in the group of white patients. According to the Kaplan—Meier survival curves, patients of African descent reached every disability stage faster than white patients ( p= 0.03, p = 0.04, and p = 0.03, respectively, for Expanded Disability Status Scale grades 3, 6, and 8). As in United States and European patients of African descent, the more severe and faster progression of multiple sclerosis seen in Brazilian primary progressive multiple sclerosis patients of African descent suggests a possibly greater effect of ethnicity rather than environment on the progression of multiple sclerosis.

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

2017 ◽  
Vol 52 (5) ◽  
pp. 473-483 ◽  
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.

scholarly journals Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
K. Daniels ◽  
P. B. van der Nat ◽  
S. T. F. M. Frequin ◽  
P. J. van der Wees ◽  
D. H. Biesma ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Primary Outcome ◽  
Clinical Effectiveness ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Real World Data ◽  
Primary Progressive ◽  
Disability Status ◽  
Pre Treatment

Background. Recently, ocrelizumab (Ocrevus®) was approved for the treatment of primary progressive multiple sclerosis (PPMS) based on data from the ORATORIO clinical trial. Real-world data about the clinical effectiveness of ocrelizumab has yet to be gathered. Objective. The aim of this study was to provide data about the clinical effectiveness of ocrelizumab for patients diagnosed with PPMS in a real-world setting. Methods. We conducted a retrospective cohort study of all patients with PPMS who started ocrelizumab treatment (n=21) in St. Antonius Hospital (Utrecht/Nieuwegein, the Netherlands) between April 2018 and December 31, 2018. Primary outcome was pre- versus post-ocrelizumab disability worsening rate (from 96 weeks prior to first ocrelizumab administration up to 24 weeks post first ocrelizumab administration). Results. Disability worsening rate while on treatment significantly differed (lower) from disability worsening rate in pre-treatment period (Z=−2.81, p≤.01). Three out of 17 patients showed a clinically relevant improvement in disability status after treatment start. Conclusion. Ocrelizumab can stabilize disability progression in patients with PPMS. Some patients even showed a clinically relevant improvement in disability status. Further research should help to identify which patients benefit most from ocrelizumab.

A single-center, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis

2009 ◽  
Vol 15 (10) ◽  
pp. 1195-1205 ◽  
Author(s):  
X. Montalban ◽  
J. Sastre-Garriga ◽  
M. Tintoré ◽  
L. Brieva ◽  
FX Aymerich ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Beneficial Effect ◽  
Interferon Beta ◽  
Progressive Multiple Sclerosis ◽  
Neurological Deterioration ◽  
Primary Progressive Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Double Blind ◽  
Primary Progressive ◽  
Disability Status

Inflammation and neurodegeneration may have differential impacts on disease evolution in the different forms of multiple sclerosis. However, a beneficial effect of immunomodulatory drugs should not be ruled out in primary progressive multiple sclerosis. Our aim is to investigate the safety and efficacy of interferon beta-1b in primary progressive multiple sclerosis. We conducted a double-blind, stratified, randomized, parallel group, phase II pilot study where patients with primary progressive multiple sclerosis or ‘transitional’ forms of multiple sclerosis received interferon beta-1b at doses of 8 MIU or placebo for 24 months. The main objective of the study was to investigate the safety and tolerability of interferon beta-1b. The primary efficacy variable was the time to neurological deterioration (Expanded Disability Status Scale) confirmed at 3 months. Seventy-three patients were included and three dropped out the study. More patients in the treatment arm had at least one related adverse event (94.4% versus 45.9%; p < 0.001); no other significant differences in safety endpoints were observed. Time to neurological deterioration was not different between trial arms (log-rank test, p = 0.3135). Statistically significant differences favoring treatment were observed for the Multiple Sclerosis Functional Composite score at several timepoints, T1 and T2 lesion volume changes at 12 and 24 months, mean number of active lesions and proportion of patients with active lesions at 24 months. We conclude that interferon beta-1b is safe and well tolerated in patients with primary progressive multiple sclerosis and transitional multiple sclerosis. Positive effects of interferon beta on secondary clinical and magnetic resonance imaging outcomes were observed, but a beneficial effect on Expanded Disability Status Scale progression was not demonstrated.

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