Sunday, 26 November 2017

Study shows a B cell depleting treatment is effective

A new study tests a B cell depleting treatment in MS. The results are interesting.



Anti-CD19 depletion kills off most B cell types, except the plasma cell (antibody secreting cell).

So when an anti-CD20, anti B cell treatment (i.e. ocrelizumab) inhibits MS, the T cellers say it is killing the 5-20% of CD20 positive T cells which contain the pathogenic cell population.

This flimsy argument accepts an unlikely event, whilst dismissing
the fact that marked CD4 T cell depletion had limited effect in MS and marked CD8 depletion with DMF (which is a moderate memory B cell depleter) is only moderately effective.

So with this new study it should now be even easier to find the pathogenic T cells, as there are very few CD19, CD3 T cells (>1%).

What do you think? 

Are the T cellers trying too hard?

The only plausible argument of an important T cell action is that B cell depletion is blocking a critical antigen presenting cell function to T cells in humans.

Agius MA, Klodowska-Duda G, Maciejowski M, Potemkowski A, Li J, Patra K, Wesley J, Madani S, Barron G, Katz E, Flor A.
Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study.Mult Scler. 2017 Nov 1:1352458517740641. 

BACKGROUND: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells.
OBJECTIVES: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS.
METHODS: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19+ B-cell count to ⩾80 cells/µL.
RESULTS: Complete B-cell depletion was observed across all doses. Infusion/injection (grade 1/2) reactions occurred in 6/15 patients receiving inebilizumab IV, 2/5 placebo IV and 1/6 inebilizumab SC. Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, mixed-drug intoxication (unrelated to inebilizumab; resulted in death) and urinary tract infection. Mean number of cumulative new gadolinium-enhancing lesions over 24 weeks was 0.1 with inebilizumab versus 1.3 with placebo; mean numbers of new/newly enlarging T2 lesions were 0.4 and 2.4, respectively.
CONCLUSION:Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.

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