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#Post#: 1187--------------------------------------------------
(AAN) Alemtuzumab's immunosuppressive effect doesn't last more
than 48 months
DIR By: agate
Date: April 23, 2016, 8:30 pm
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Presented at the annual AAN conference in Vancouver, BC, in
April 2016:
--- Quote ---
> S2.008 - Alemtuzumab Long Term Immunological Study: The
Immunosuppressive Effect Does Not Last More Than 48 Months
>
> Luca Durelli,1Stefania De Mercanti,1Simona Rolla,2Angele
Cucci,1Valentina Bardina,2Eleonora Cocco,3Anton Vladic,4Silva
Soldo-Butkovic,5Mario Habek,4Ivan Adamec,4Pietro Annovazzi,6Dana
Horakova,7Franco Novelli,2Marinella Clerico8
>
> 1Orbassano, Italy, 2Torino, Italy, 3Cagliari, Italy, 4Zagreb,
Croatia, 5Osijek, Croatia, 6Gallarate, Italy, 7Prague, Czech
Republic, 8Orbassano (TO), Italy
>
> Disclosures
>
> L. Durelli: None. S. De Mercanti: None. S. Rolla: None. A.
Cucci: None. V. Bardina: None. E. Cocco: None. A. Vladic: None.
S. Soldo-Butkovic: None. M. Habek: None. I. Adamec: None. P.
Annovazzi: ; Dr Annovazzi received personal compensation for
consulting, speaking and serving on a scientific advisory board
from Biogen Idec, Novartis and Teva pharmaceuticals. D.
Horakova: ; Support for research activities from Biogen Idec. F.
Novelli: None. M. Clerico: None.
>
> OBJECTIVE:
>
> Phenotypic and functional analysis of CD4+ T cell subsets and
of immunologically relevant molecules mRNA serum levels after
alemtuzumab in relapsing remitting multiple sclerosis(RRMS)
patients: A four-year follow-up.
>
> BACKGROUND:
>
> Alemtuzumab induces a long-standing lymphopenia, particularly
of T CD4+ subset, and it is highly effective in RRMS
>
> DESIGN/METHODS:
>
> Multicenter follow-up of 29 alemtuzumab-treated RRMS patients
from 6 European sites in the CARE-MS I and CARE-MS II trials.
Patients received two courses of alemtuzumab at month 0 and 12.
Clinical and immunological evaluation were performed at months
0, 6, 12, 18, 24, 36 and 48. The percentages of Treg, Th1 and
Th17 cells in the peripheral blood mononuclear cells(PBMC) were
evaluated by FACS analysis. mRNA levels of cytokines,
chemokines, chemokine receptors and transcriptional factors with
pro-inflammatory (IL-1β, IL-2, IL-6, IL-12, IL-17A, IL-17F,
IL-21, IL-22, IL-23, IL-26, IFN-γ, Tbet, RORC, TNF-α,
CCR3, CCR4, CCR5, CCR6, CXCR3, CXCL10, CCL20, VLA4) or
anti-inflammatory function (IL-10, IL-27, TGF-β and FoxP3)
were quantified by TaqManŽ low density array(TLDA) real-time
polymerase chain reaction in whole blood. Treg suppressor
activity on Myelin basic protein(MBP)-specific Th17 and Th1
cells was assessed by IL-17 and IFN-γ ELISPOT on total PBMC
and PBMC depleted of CD25highT cells.
>
> RESULTS:
>
> No patient received further alemtuzumab courses after the
first two years. CD4+ lymphocyte percentage decreased and slowly
returned to basal levels only at Month 48. Within this
population, no significant variation was observed in Th1 and
Th17 cells, with the exception of an increase of Th17 cells in
patients with a documented relapse. Treg cells percentage and
suppressive function significantly increased at Month 24 and
returned to baseline levels within Month 48.
>
> CONCLUSIONS:
>
> The long-term follow-up of immune system reconstitution showed
that alemtuzumab effects lasted not more that 48 months.
Clinical and MRI follow-up could suggest the need for repeated
alemtuzumab courses.
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