Short-term B-cell Depletion in Relapsing Multiple Sclerosis

2019 ◽  
Author(s):  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Short Term ◽  
Relapsing Multiple Sclerosis

scholarly journals Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study

2021 ◽  
pp. 135245852110444
Author(s):  
Amit Bar-Or ◽  
Heinz Wiendl ◽  
Xavier Montalban ◽  
Enrique Alvarez ◽  
Maria Davydovskaya ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Geometric Mean ◽  
Cell Depletion ◽  
Maximum Plasma ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Cell Counts ◽  
Phase 2 Study ◽  
Relapsing Multiple Sclerosis

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC τ) and maximum plasma concentration ( Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUC τ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

B-Cell Depletion and COVID-19 Severity in Multiple Sclerosis: Remaining Challenges

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012754
Author(s):  
Joep Killestein ◽  
Menno M. Schoonheim ◽  
Rhonda R. Voskuhl
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals Use of B-Cell–Depleting Therapy in Women of Childbearing Potential With Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

2022 ◽  
pp. 10.1212/CPJ.0000000000001147
Author(s):  
Alexandra Galati ◽  
Thomas McElrath ◽  
Riley Bove
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Spectrum Disorder ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Childbearing Potential ◽  
Pregnancy And Postpartum

AbstractPurposeof Review: There is considerable heterogeneity in the use of B cell depletion in women of childbearing age, likely driven at least in part by the discrepancy between the product labels and what is known about the physiology of IgG1, including breastmilk and placental transfer.Recent Findings:We provide practical considerations on the use of this medication class in women of childbearing potential. We discuss pre-pregnancy planning including vaccinations, safety of B cell depletion during pregnancy as well as postpartum considerations including breastfeeding.Summary:B cell depleting monoclonal antibodies have shown to be effective for pre-pregnancy and postpartum prevention of inflammatory activity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). B cell depleting therapies are large IgG1 monoclonal antibodies which have minimal transfer across the placenta and into breastmilk. Consideration of risks and benefits of these therapies should be considered in counseling women planning pregnancy and postpartum.

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

2020 ◽  
pp. 135245852091837 ◽  
Author(s):  
Edward Fox ◽  
Amy E Lovett-Racke ◽  
Matthew Gormley ◽  
Yue Liu ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Optimal Dose ◽  
Cell Depletion ◽  
Controlled Study ◽  
Lesion Volume ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Anti Cd20

Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies

2017 ◽  
Vol 24 (9) ◽  
pp. 1224-1233 ◽  
Author(s):  
Nicky Dunn ◽  
Alexander Juto ◽  
Malin Ryner ◽  
Ali Manouchehrinia ◽  
Luca Piccoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Clinical Outcomes ◽  
Clinical Relevance ◽  
Cell Depletion ◽  
Enzyme Linked Immunosorbent Assay ◽  
B Cell Depletion ◽  
Serum Samples ◽  
Cross Sectional ◽  
Cell Counts

Background: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. Objective: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. Methods: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house–validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records. Results: ADAs were detected in 37% of relapsing–remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive. Conclusion: Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.

scholarly journals Prolonged COVID-19 Infection in a Patient with Multiple Sclerosis and Rituximab-Treatment

2021 ◽  
Author(s):  
Michael Turner ◽  
Wolfgang Grisold ◽  
Christoph Wenisch ◽  
Christian Krestan ◽  
Ludwig Erlacher
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
Antibiotic Treatment ◽  
Rapid Recovery ◽  
Cell Depletion ◽  
Disease Course ◽  
B Cell Depletion ◽  
Persistent Fever ◽  
Bilateral Lung

Abstract We present a prolonged disease course in a 32-year old woman with COVID-19 and multiple sclerosis on rituximab-treatment for three years. The patient was admitted to the hospital for COVID-19 and had persistent fever, cough and radiologic bilateral lung opacities over the course of 29 days. After ineffective antibiotic treatment and the detection that she had no antibodies against SARS-CoV-2 convalescent plasma was administered with rapid recovery ensuing. While there is evidence convalescent plasma is not superior to placebo for COVID-19 in general its role in patients with B-cell depletion and COVID-19 remains to be examined further.

Sign in / Sign up

Export Citation Format

Share Document