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Optic Neuropathies Associated With Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMO-SD)
Published in Vivek Lal, A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
Long-term immune-suppression/Disease modifying therapy (DMT) is advocated in all cases of CRION and NMO-SD in order to avoid future relapses and associated cumulative disability. First-line agents used are azathioprine, rituximab and mycophenolate mofetil (MMF was used as a second-line drug by the neuromyelitis optica study group). Drugs like methotrexate and mitoxantrone are considered second-line agents. Drugs for which clinical trials are underway are tocilizumab, inebilizumab, eculizumab, aquapuromab (40). A general approach to treatment is given in Figure 5.11.
Transitioning immunotherapy in neuromyelitis optica spectrum disorder – when and how to switch
Published in Expert Opinion on Biological Therapy, 2022
Anastasia Vishnevetsky, Tamara B. Kaplan, Michael Levy
Inebilizumab is a humanized, afucosylated IgG1 monoclonal antibody that binds to the B cell surface marker, CD19, leading to antibody-dependent cytotoxicity. Like rituximab, inebilizumab depletes B cells. However, it also depletes B cell precursors (i.e. pro-B cells), as well as plasmablasts, and short-lived plasma cells which express the CD19 but not the CD20 surface marker. The pharmacodynamic effect of inebilizumab on B cells occurs within approximately 4 weeks, with a significant reduction in circulating B cells to less than 10% of baseline [16]. In the 2019 clinical trial N-Momentum, 21 (12%) of 174 of those who received inebilizumab had an attack, compared to 22 (39%) of 56 of those who received placebo, which calculates to a 76% reduction in risk. In this trial, 91% of subjects in both the placebo and treatment arms were AQP4-IgG positive. The randomized control period was 28 weeks, and subjects were randomized 3:1 to receive inebilizumab or placebo. No other immunosuppressive therapies were used [16]. Like rituximab, inebilizumab is typically administered as an intravenous infusion every 6 months after an induction protocol [16].
Rituximab in Myasthenia Gravis - Where do we stand?
Published in Expert Opinion on Biological Therapy, 2021
Zaeem A. Siddiqi, Wasim Khan, Faraz S. Hussain
Belimumab is a monoclonal antibody against the B-cell activating factor. A phase II double-blind RCT that included gMG patients with anti-AChR Ab or anti-MuSK Ab did not meet the primary end-point [36]. The small sample size and the mild clinical severity of patients may have jeopardized the final results.Iscalimab (CFZ-533) is a novel human IgG1 anti-CD40 monoclonal antibody that prevents B-cell activation without causing B-cell depletion by targeting CD40-CD40 ligand (CD40L) interaction [37]. A phase II RCT did not show any statistically significant difference between the primary (QMG) and multiple secondary outcomes (MGC, MG-ADL, MG-QoL15) at the pre-specified observation periods [38].Inebilizumab is a humanized high-affinity anti-CD19 monoclonal antibody that depletes almost all B-cells, including precursor-plasma cells through antibody-dependent cell-mediated cytotoxicity. It was recently approved in the USA for the treatment of neuromyelitis optica spectrum disorder. A multicenter phase III, double-blind, RCT that will enrol approximately 252 subjects in MG (172 AChR-Ab+ and 80 MuSK-Ab+) is underway [39].
Investigational immunosuppressants in early-stage clinical trials for the treatment of multiple sclerosis
Published in Expert Opinion on Investigational Drugs, 2018
Alberto Gajofatto, Marco Turatti
In the above-mentioned phase 1 trial, enrolled patients (n = 28) were randomized 3:1 in five cohorts to receive 2 doses (days 1 and 15) of 30, 100, or 600 mg IV MEDI551, or a single dose (day 1) of 60 or 300 mg SC MEDI551, or placebo. Patients were followed until CD19 + B-cell count returned to the lower limit of normal (80 cells/µL) or up to the end of the treatment period (day 169). A rapid decline in B-cell counts was observed for all MEDI-551 dose groups; the higher the drug dose, the longer the B-cell depletion. Infusion/injection reactions occurred in 6/15 (40%) patients treated with IV inebilizumab, 2/6 (33%) treated with SC inebilizumab, and 2/7 (29%) treated with placebo. Other adverse events occurring in more than one case treated with inebilizumab were pyrexia, nasopharyngitis, oral herpes, and increased blood pressure (n = 2 each). Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, urinary tract infection, and mixed-drug intoxication, which resulted in death although it was judged unrelated to study drug. The mean number of cumulative new gadolinium-enhancing lesions on brain MRI over 169 days was 0.1 in the MEDI-551 group versus 1.1 in the placebo group, while the mean number of new/enlarging T2 lesions at day 169 was 0.4 in the MEDI-551 group versus 2.2 in the placebo group. Although inebilizumab is still at a very early stage of clinical research in MS, the prolonged B-cell depletion, safety profile, and efficacy on MRI measures of inflammatory activity associated with this drug hold promise for its potential validity as a novel therapeutic option for relapsing forms of MS, to be confirmed in further studies.