Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study

CNS Drugs ◽  
2021 ◽  
Author(s):  
Serena Palmeri ◽  
Marta Ponzano ◽  
Federico Ivaldi ◽  
Alessio Signori ◽  
Caterina Lapucci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Observational Study ◽  
Disease Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Reconstitution ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731880163
Author(s):  
Gordon Mazibrada ◽  
Charlotte Sharples ◽  
Ines Perfect
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Observational Study ◽  
Disease Activity ◽  
Relapse Rate ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
The Uk ◽  
Relapsing Remitting Multiple Sclerosis

Background Fingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK. Objective To evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service. Methods This was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed. Results In 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed. Conclusion Fingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

scholarly journals Discontinuation and dose reduction of rituximab in relapsing–remitting multiple sclerosis

2021 ◽  
Author(s):  
Malin Boremalm ◽  
Peter Sundström ◽  
Jonatan Salzer
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Dose Reduction ◽  
Inflammatory Disease ◽  
University Hospital ◽  
Full Dose ◽  
Reduced Dose ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Abstract Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of < 1000 mg yearly. The patients served as their own controls by contributing patient years on full dose, reduced dose, and off treatment. Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus < 0.01 and 0.02, p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (< 0.01 versus 0 and 0.02, p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (< 1000 mg yearly) is sufficient to maintain suppression of inflammatory disease activity in patients with stable disease.

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

2020 ◽  
Vol 91 (3) ◽  
pp. 271-277 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Mancinelli ◽  
Shalom Haggiag ◽  
Cinzia Cordioli ◽  
Laura De Giglio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Second Year ◽  
Remitting Multiple Sclerosis ◽  
A Minor ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Minimal Evidence

ObjectiveThis study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.MethodsWe retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and <3 new T2 lesions; medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).ResultsAt follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.ConclusionsEarly marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.

Ingested IFN-α has biological effects in humans with relapsing-remitting multiple sclerosis

1997 ◽  
Vol 3 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Staley A Brod ◽  
Ronald H Kerman ◽  
Laura D Nelson ◽  
Gailen D Marshall ◽  
Evelyn M Henninger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Biological Effects ◽  
Intercellular Adhesion Molecule ◽  
Type I ◽  
Recombinant Type ◽  
Relapsing Remitting ◽  
Ifn Γ ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-γ production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-α was non-toxic and had biological effects in humans. ingested hrIFN-α showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100 000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-I (sICAM-I), a surrogate measure for disease activity in MS, was found after ingesting 10 000 and 30 000 units IFN-α The RRMS subjects also showed decreased IL-2 secretion after ingesting 10 000 units IFN-α, and decreased IFN-γ, TGF-β and IL-10 production after ingesting 30 000 units IFN-α. The decreased secretion of IFN-γ and IL-2 by ingested IFN-α suggests that oral IFN-α may cause a functional inhibition of Th I-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-α as a biological response modifier in humans.

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