Author Topic: (ECTRIMS abst.) Long-term follow-up of early cohorts (alemtuzumab in MS)  (Read 167 times)

0 Members and 2 Guests are viewing this topic.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
Presented at the ECTRIMS conference in Barcelona, October 7-10, 2015:

Quote
Alemtuzumab in multiple sclerosis: long-term follow-up of the early cohorts

J.W.L. Brown1,2, O. Tuohy1, O. Kousin-Ezewu1, L. Azzopardi1, T. Button1, C. Mccarthy1, T. Alli3, C. Callan3, M. Folks3, S. Heller3, H. Laidley3, B. Nourallah3, C. O’Neill3, D. Obute3, R. Piper3, O. Prankerd Smith3, H. Wickham3, X. Zheng3, K. May1, A. Gerritz1, D.A.S. Compston1, J.L. Jones1, A.J. Coles1

1Department of Clinical Neurosciences, University of Cambridge, Cambridge, 2University College London Institute of Neurology, Queen Square Multiple Sclerosis Centre, NMR Research Unit, London, 3University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom

Background:

In relapsing remitting multiple sclerosis (RRMS) alemtuzumab is highly effective at reducing relapses and disability accrual, and is now widely licensed. We present the efficacy and safety data from two early single-arm studies of alemtuzumab in RRMS (median follow-up 10.1 years), and contrast the findings with a secondary progressive (SPMS) cohort (median follow-up 19.8 years). These cohorts informed the design of subsequent clinical trials.

Methods:

We treated 86 patients with highly active RRMS (median two relapses per year before treatment; median (standard deviation (SD)) Expanded Disability Status Scale (EDSS) score at baseline: 3.5 (2.0)) plus 36 patients with SPMS (baseline EDSS: 6 (0.9)). Relapses, change in disability and adverse events were recorded. Univariate and logistic regression analyses were used to identify baseline variables associated with a higher risk of disability progression.

Results:

RRMS

After 10.1 years, 39/86 patients (45%) remained relapse-free. Forty-one patients (48%) required two cycles of alemtuzumab (the standard treatment course), while relapses triggered re-treatment to a total of three cycles (in 33 patients (38%)), four cycles (in nine patients (10%)) and five cycles (in three patients (3%)). The EDSS remained largely unchanged 10.1 years later (3.5, SD 2.2; p NS). One patient died, unrelated to multiple sclerosis.

SPMS

Patients received one (n=28), two (n=7) or three (n=1) cycles of alemtuzumab. After 19.8 years, the median EDSS had significantly increased from 6 (SD 0.9) to 8.75 (SD 1.4), p< 0.0001, and 13 patients had died.

Adverse events

Secondary clinical autoimmunity occurred in 41/86 (48%) of the RRMS cohort and 16/36 (44%) of the SPMS cohort, a median 18.0 and 28.5 months respectively after the last alemtuzumab treatment. The thyroid gland was most commonly affected.

Conclusions:

Alemtuzumab causes long-lasting disease stabilization in highly active RRMS, but has no effect on disability progression in SPMS. Secondary clinical autoimmunity occurs in approximately half of patients.

__________________
Disclosure

J William L Brown: nothing to disclose;
Orla Tuohy: nothing to disclose;
Onajite Kousin-Ezewu: nothing to disclose;
Laura Azzopardi: nothing to disclose;
Tom Button: nothing to disclose;
Claire McCarthy: nothing to disclose;
Theo Alli: nothing to disclose;
Caitriona Callan: nothing to disclose;
Matthew Folks: nothing to disclose;
Simon Heller: nothing to disclose;
Hannah Laidley: nothing to disclose;
Basil Nourallah: nothing to disclose;
Cormac O’Neill: nothing to disclose;
Daniel Obute: nothing to disclose;
Robert Piper: nothing to disclose;
Olivia Prankerd Smith: nothing to disclose;
Helena Wickham: nothing to disclose;
Xueying Zheng: nothing to disclose;
Karen May: nothing to disclose;
Anna Gerritz: nothing to disclose;
D Alastair S Compston has received lecture fees and travel reimbursements from Genzyme (a Sanofi company) on behalf of himself and the University of Cambridge; and he is a paid scientific adviser to the Lundbeck Foundation;
Joanne L Jones has received consulting fees and lecture fees from Genzyme (a Sanofi company).
Alasdair J Coles has received honoraria and travel expenses and the department has received research grants, from Genzyme (a Sanofi company).
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.