ECTRIMS eLearning

Durable effect of alemtuzumab on MRI lesion outcomes over 5 years in patients with highly active relapsing-remitting multiple sclerosis who had an inadequate response to prior therapy (CARE-MS II)
Author(s): ,
G Comi
Affiliations:
Vita-Salute San Raffaele University, Milan, Italy
,
R Berkovich
Affiliations:
University of Southern California, Los Angeles, CA, United States
,
A Rovira
Affiliations:
University Hospital Vall d'Hebron, Barcelona, Spain
,
D Pelletier
Affiliations:
University of Southern California, Los Angeles, CA, United States
,
S Schippling
Affiliations:
Neuroimmunology and Multiple Sclerosis Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland
,
A Traboulsee
Affiliations:
University of British Columbia, Vancouver, BC, Canada
,
P Vermersch
Affiliations:
University of Lille, Lille, France
,
D.H Margolin
Affiliations:
Sanofi Genzyme, Cambridge, MA, United States
,
K Thangavelu
Affiliations:
Sanofi Genzyme, Cambridge, MA, United States
,
D.L Arnold
Affiliations:
NeuroRx Research;Montréal Neurological Institute and Hospital, Montréal, QC, Canada
on behalf of the CARE-MS II Investigators
on behalf of the CARE-MS II Investigators
Affiliations:
ECTRIMS Learn. 09/15/16; 146453; P613
Abstract

Abstract: P613

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: In the CARE-MS II study (NCT00548405), patients with relapsing-remitting multiple sclerosis (RRMS) with highly active disease (HAD; defined as ≥2 relapses in the year before randomisation and ≥1 gadolinium [Gd]-enhancing lesion) and an inadequate response (≥1 relapse) to prior therapy at baseline (BL) showed significantly reduced clinical and MRI disease activity with alemtuzumab versus SC IFNB-1a over 2 years. An extension study (NCT00930553) has shown clinical efficacy to be durable through 5 years in the absence of continuous treatment in patients with HAD.

Goal: To evaluate 5-year MRI outcomes in alemtuzumab-treated patients with HAD at BL.

Methods: In CARE-MS II, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). Patients who completed CARE-MS II could enter the extension, with as-needed alemtuzumab retreatment for relapse or MRI activity. Another DMT could be initiated per investigator discretion. Assessments: MRI disease activity (defined as new Gd-enhancing T1 and new/enlarging T2 hyperintense lesions), brain volume loss (BVL), and no evidence of disease activity (NEDA).

Results: 92 of 103 (89%) alemtuzumab-treated patients with HAD completed the CARE-MS II core study and entered the extension; of those, 90 patients (98%) remained on study through 5 years. MRI activity remained low through the extension; in Year 5, most patients had no Gd-enhancing T1 lesions (92%) and no new/enlarging T2 hyperintense lesions (70%), and most achieved annual MRI NEDA (70%). In addition, most patients also had no new T1 hypointense lesions (89% in Year 5). Median yearly BVL decreased progressively over 3 years and remained low in Year 5 (-0.13%/year). Over half of patients with HAD achieved NEDA (clinical and MRI) in each year of the extension (54% in Year 5). These results were achieved with 62% of patients with HAD receiving no additional treatment after their initial 2 courses of alemtuzumab.

Conclusion: Alemtuzumab efficacy on MRI outcomes was durable through 5 years in patients with HAD and an inadequate response to prior therapy, reinforcing findings on clinical outcomes in these patients. MRI outcomes and NEDA observed with alemtuzumab in the HAD population were consistent with those observed in the overall study population. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients with HAD.

Disclosure:

Study support:
Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.

GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva); lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi Genzyme, Serono Symposia International Foundation, and Teva).

RB:
Advisory boards and consulting (Acorda, Avanir, Bayer, Biogen, Novartis, Questcor, Sanofi Genzyme, and Teva).

AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).

DP:
Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Vertex).

SS: Research grants (Bayer, Biogen, and Sanofi Genzyme); consulting/speaking fees (Bayer, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).

AT:
Consulting fees (Biogen, Chugai, MedImmune, Novartis, Roche, Sanofi Genzyme, Serono, and Teva Innovation); principal investigator on clinical trials (Roche and Sanofi Genzyme).

PV: Consulting and/or speaking fees (Almirall, Bayer, Biogen, GlaxoSmithKline, Novartis, Merck Serono, Sanofi Genzyme, and Teva); research support (Bayer, Biogen, Merck Serono, and Novartis).

DM and KT:
Employees of Sanofi Genzyme.

DLA: Honoraria (Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Medimmune, Merck Serono, Novartis, Receptos, Roche, Sanofi Aventis, Sanofi Genzyme, and Teva); employee (NeuroRx).

Abstract: P613

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: In the CARE-MS II study (NCT00548405), patients with relapsing-remitting multiple sclerosis (RRMS) with highly active disease (HAD; defined as ≥2 relapses in the year before randomisation and ≥1 gadolinium [Gd]-enhancing lesion) and an inadequate response (≥1 relapse) to prior therapy at baseline (BL) showed significantly reduced clinical and MRI disease activity with alemtuzumab versus SC IFNB-1a over 2 years. An extension study (NCT00930553) has shown clinical efficacy to be durable through 5 years in the absence of continuous treatment in patients with HAD.

Goal: To evaluate 5-year MRI outcomes in alemtuzumab-treated patients with HAD at BL.

Methods: In CARE-MS II, patients received 2 courses of alemtuzumab 12 mg (Month 0: 5 days; Month 12: 3 days). Patients who completed CARE-MS II could enter the extension, with as-needed alemtuzumab retreatment for relapse or MRI activity. Another DMT could be initiated per investigator discretion. Assessments: MRI disease activity (defined as new Gd-enhancing T1 and new/enlarging T2 hyperintense lesions), brain volume loss (BVL), and no evidence of disease activity (NEDA).

Results: 92 of 103 (89%) alemtuzumab-treated patients with HAD completed the CARE-MS II core study and entered the extension; of those, 90 patients (98%) remained on study through 5 years. MRI activity remained low through the extension; in Year 5, most patients had no Gd-enhancing T1 lesions (92%) and no new/enlarging T2 hyperintense lesions (70%), and most achieved annual MRI NEDA (70%). In addition, most patients also had no new T1 hypointense lesions (89% in Year 5). Median yearly BVL decreased progressively over 3 years and remained low in Year 5 (-0.13%/year). Over half of patients with HAD achieved NEDA (clinical and MRI) in each year of the extension (54% in Year 5). These results were achieved with 62% of patients with HAD receiving no additional treatment after their initial 2 courses of alemtuzumab.

Conclusion: Alemtuzumab efficacy on MRI outcomes was durable through 5 years in patients with HAD and an inadequate response to prior therapy, reinforcing findings on clinical outcomes in these patients. MRI outcomes and NEDA observed with alemtuzumab in the HAD population were consistent with those observed in the overall study population. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continuous treatment for RRMS patients with HAD.

Disclosure:

Study support:
Sanofi Genzyme and Bayer HealthCare Pharmaceuticals.

GC: Consulting fees (Actelion, Bayer, Merck Serono, Novartis, Sanofi Genzyme, and Teva); lecture fees (Bayer, Biogen Dompé, Merck Serono, Novartis, Sanofi Genzyme, Serono Symposia International Foundation, and Teva).

RB:
Advisory boards and consulting (Acorda, Avanir, Bayer, Biogen, Novartis, Questcor, Sanofi Genzyme, and Teva).

AR: Consulting and/or speaking fees (Bayer, Biogen, Bracco, Novartis, Sanofi Genzyme, and Stendhal).

DP:
Consulting and/or speaking fees and grant/research support (Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Vertex).

SS: Research grants (Bayer, Biogen, and Sanofi Genzyme); consulting/speaking fees (Bayer, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).

AT:
Consulting fees (Biogen, Chugai, MedImmune, Novartis, Roche, Sanofi Genzyme, Serono, and Teva Innovation); principal investigator on clinical trials (Roche and Sanofi Genzyme).

PV: Consulting and/or speaking fees (Almirall, Bayer, Biogen, GlaxoSmithKline, Novartis, Merck Serono, Sanofi Genzyme, and Teva); research support (Bayer, Biogen, Merck Serono, and Novartis).

DM and KT:
Employees of Sanofi Genzyme.

DLA: Honoraria (Acorda, Bayer, Biogen, Genentech, GlaxoSmithKline, Medimmune, Merck Serono, Novartis, Receptos, Roche, Sanofi Aventis, Sanofi Genzyme, and Teva); employee (NeuroRx).

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