Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity

Kousin-Ezewu, Onajite; Azzopardi, Laura; Parker, Richard; Tuohy, Orla; Compston, Alastair; Coles, Alasdair; Jones, Joanne L.

doi:10.1212/wnl.0000000000000520

Cited by 54 publications

(54 citation statements)

References 11 publications

(14 reference statements)

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“…In phase III studies, alemtuzumab treatment beyond the initial two courses was offered if a relapse occurred or if a patient accumulated ⩾2 unique MRI lesions (either Gd-enhancing lesions and/or new or enlarging T 2 lesions). Lymphocyte reconstitution rate does not appear to predict breakthrough disease activity, and use of lymphocyte counts as a biomarker to indicate retreatment has been discouraged [Kousin-Ezewu et al 2014]. In clinical practice, it may be appropriate to monitor alemtuzumab efficacy by MRI.…”

Section: The Decision To Re-treat With Alemtuzumabmentioning

confidence: 99%

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Havrdová

Horáková

Kovářová

2015

Ther Adv Neurol Disord

148

129

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Alemtuzumab is a humanized monoclonal antibody therapy that has recently been approved in over 30 countries for patients with active relapsing-remitting multiple sclerosis. It acts by targeting CD52, an antigen primarily expressed on T and B lymphocytes, resulting in their depletion and subsequent repopulation. The alemtuzumab clinical development program used an active comparator, subcutaneous interferon beta-1a, to show that alemtuzumab is a highly efficacious disease-modifying therapy, with benefits on relapses, disability outcomes, and freedom from clinical disease and magnetic resonance imaging activity. The safety profile was consistent across studies and no new safety signals have emerged during follow-up in the extension study. Infusion-associated reactions are common with alemtuzumab, but rarely serious. Infection incidence was elevated with alemtuzumab in clinical studies; most infections were mild or moderate in severity. Autoimmune adverse events occurred in approximately a third of patients, manifesting mainly as thyroid disorders, and less frequently as immune thrombocytopenia or nephropathy. A comprehensive monitoring program lasting at least 4 years after the last alemtuzumab dose allows early detection and effective management of autoimmune adverse events. Further experience with alemtuzumab in the clinic will provide needed long-term data.

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Section: The Decision To Re-treat With Alemtuzumabmentioning

confidence: 99%

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Havrdová

Horáková

Kovářová

2015

Ther Adv Neurol Disord

148

129

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“…Alemtuzumab is a humanized monoclonal antibody which targets CD52, a 12 amino acid glycosylated glycosylphosphatidylinositol-linked protein expressed on the cell surface of lymphocytes, monocytes, macrophages, eosinophils and NK cells.1,2 The anti-CD52 effect of alemtuzumab results in rapid and profound depletion of circulating lymphocytes following intravenous infusion, as a result of antibody-dependent cell-mediated cytotoxicity.3 However, CD52 is not expressed on haematopoietic precursors, so allowing beneficial immune reconstitution.4,5 Although exhibiting a degree of individual variability, the pattern of immune reconstitution is not thought to reliably predict disease activity. [6][7][8] Early open label studies demonstrated a marked reduction of relapse rates and slowing of disability accumulation when given early in the course of disease. 9-14 One subsequent phase II trial15 and two phase III trials,16,17 both against an active comparator, have confirmed this effect, and open label follow-up data for the phase II trial also demonstrates durability of effect over five years of followup.…”

Section: Introductionmentioning

confidence: 99%

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort

et al. 2016

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Background: Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve. Objectives: To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab. Methods: Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review. Results: One hundred patients were identified with a mean follow-up of 6.1 years (range 1–13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 ( p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity. Conclusion: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime.

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“…However, in a more detailed analysis published in this issue of Neurology by Kousin-Ezewu et al, 8 these initial observations could not be confirmed.…”

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confidence: 84%

Immune reconstitution and treatment response in multiple sclerosis following alemtuzumab

Robertson

Scolding

2014

Neurology

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Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity

Abstract: This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab.

Cited by 54 publications

References 11 publications

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort

Immune reconstitution and treatment response in multiple sclerosis following alemtuzumab

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