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Multiple sclerosis

Which drug reduces the autoimmune risks of alemtuzumab?

Mitigating alemtuzumab-associated autoimmunity in MS: a “whack-a-mole” B-cell depletion strategy

Meltzer E, Campbell S, Ehrenfeld B, et al.

Neurol Neuroimmunol Neuroinflamm 2020; 7:e868.

Abstract

Objective

To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.

Methods

In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m2), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.

Results

Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed.

Conclusions

An anti-CD20 “whack-a-mole” B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation.

Classification of evidence: This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.

This paper is cited in the Neurochecklist:

Alemtuzumab: management of complications

Abstract link

By <a href=”//commons.wikimedia.org/wiki/User:Fvasconcellos” title=”User:Fvasconcellos”>Fvasconcellos</a> 02:03, 28 May 2007 (UTC) – From <a href=”https://en.wikipedia.org/wiki/Protein_Data_Bank&#8221; class=”extiw” title=”w:Protein Data Bank”>PDB</a> entry <a rel=”nofollow” class=”external text” href=”http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1CE1″>1CE1</a&gt;.More information: James LC, Hale G, Waldmann H, Bloomer AC, Waldman H (1999). “1.9 Å structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen”. J Mol Biol 289 (2): 293–301. <a class=”external mw-magiclink-pmid” rel=”nofollow” href=”//www.ncbi.nlm.nih.gov/pubmed/10366506?dopt=Abstract”>PMID 10366506</a>. <a href=”https://en.wikipedia.org/wiki/Digital_object_identifier&#8221; class=”extiw” title=”w:Digital object identifier”>doi</a>:<a rel=”nofollow” class=”external text” href=”https://doi.org/10.1006%2Fjmbi.1999.2750″>10.1006/jmbi.1999.2750</a&gt;., Public Domain, Link

By Ibrahim Imam

I am a UK Neurologist keen on general neurology, but with an interest in neuromuscular diseases. I maintain the neurology searchable database, www.neurochecklists.com. I also blog at www.theneurologylounge.com. I share and discuss current issues around clinical neurology. I hope you find my blogs enlightening, practical, and even entertaining.

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