Contributions
Abstract: EP1647
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The AMS3 study tracked the development of a system to improve pathology monitoring and alerting of abnormalities in patients treated with alemtuzumab for MS.
Aims: To report the clinical & MRI outcomes of 10 patients with very active relapsing remitting MS treated with alemtuzumab and followed for 2 years.
Methods: Ten patients selected by rank order of need from 30 nominated by neurologists from Australia, with highly active MS and failure or unsuitability for other therapies. Clinical and MRI measures are reported given the unique severe nature of this cohort. The endpoints of the study are reported separately.
Results: At baseline (BL), mean age = 36 (24 - 57), disease duration = 5.3Y (2 - 10), relapses prior 12 months = 2.3 (1-5), EDSS = 3.05 (2 - 4). Mean prior MS therapies = 2.9 (1-6 - all had prior natalizumab, 9 JC+). The reason for alemtuzumab given was: relapse on fingolimod (6) or DMF(2); relapse on natalizumab, JC- (1); relapse while pregnant, JC+ (1).
During the study, 3/10 patients had relapses. One patient had 4, without change in exam or MRI. Two other patients had 2 relapses each, with new features and MRI lesions. The annualised relapse rate declined to 0.4 (from 2.9), an 86% ARR reduction. The mean EDSS declined from BL=3.05, to Y1=2.25, and Y2=2.22. Seven patients had confirmed disability improvement, 2 unchanged, 1 confirmed disability worsening. That patient had cord relapses with pial spinal cord enhancement and cerebral Gd+ lesions unchanged over 2 years suggesting a non-MS disease such as sarcoid.
On completion, mean MRI-T2-hyperintense lesion volume increased 3.6% BL-Y1, then declined -3.1% Y1 - Y2. Atrophy (SIENA): average -0.97% (SD 0.68%) brain atrophy BL-Y1 and -0.29% (SD 0.53%) Y1-Y2. Both suggest a contribution of active disease and subsequent pseudoatrophy in the first year with brain volume changes approximately normal in the second year. The mean Gd lesion number at entry was 9.2 (0-26), Y1 1.9 (0-13), Y2 0.11 (0-1). Conversion of enhancing lesions to T1-black holes: 4 patients at BL (n lesions = 1,1,2,2), no Y1 Gd lesions converted to black holes.
Conclusions: Alemtuzumab is a highly effective treatment for MS, even in a highly active cohort with considerably more pre-treatment than patients in the pivotal trials. Careful review of the diagnosis is needed in atypical cases before alemtuzumab treatment. Marked improvement in relapse rates, new Gd lesions, and second year brain atrophy occurred.
Disclosure:
Acknowledgments:
The authors wish particularly to acknowledge the substantial intellectual contributions, study design inputs, procedural support over the course of the study and reviews by Richard Worrell, B. Pharm. Mr Worrell is an employee of Sanofi-Aventis Australia Pty Ltd. We also wish to acknowledge significant contributions to study design and implementation by Jamshed Ahmed. Dr Ahmed was an employee of Sanofi-Aventis Australia Pty Ltd.
Disclosures
Sanofi-Aventis Australia Pty Ltd provided funding and product for this study. This company was not involved in the design, collection, analysis or interpretation of the study, but they were given the opportunity to review this abstract prior to submission. The decision to submit for publication was made by the authors independently.
S. Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.
S. Riminton has received payments for grant support from Octapharma and CSL Bioplasma, travel support from Sanofi-Genzyme, membership on advisory councils from Merck, Sanofi-Genzyme, National Blood Authority of Australia and Baxter Healthcare, speaker's bureau from Sanofi-Genzyme, and Biogen, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
T. Dugal has received travel support from Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
D. Gahan is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
F. Fitzgerald is an employee of Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
K. Buzzard has received educational support from Sanofi-Genzyme, Teva and Biogen, speakers honorarium from Biogen, Novartis and Sanofi-Genzyme, and membership on advisory boards from Merck.
D. Erickson reports no disclosures
Abstract: EP1647
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: The AMS3 study tracked the development of a system to improve pathology monitoring and alerting of abnormalities in patients treated with alemtuzumab for MS.
Aims: To report the clinical & MRI outcomes of 10 patients with very active relapsing remitting MS treated with alemtuzumab and followed for 2 years.
Methods: Ten patients selected by rank order of need from 30 nominated by neurologists from Australia, with highly active MS and failure or unsuitability for other therapies. Clinical and MRI measures are reported given the unique severe nature of this cohort. The endpoints of the study are reported separately.
Results: At baseline (BL), mean age = 36 (24 - 57), disease duration = 5.3Y (2 - 10), relapses prior 12 months = 2.3 (1-5), EDSS = 3.05 (2 - 4). Mean prior MS therapies = 2.9 (1-6 - all had prior natalizumab, 9 JC+). The reason for alemtuzumab given was: relapse on fingolimod (6) or DMF(2); relapse on natalizumab, JC- (1); relapse while pregnant, JC+ (1).
During the study, 3/10 patients had relapses. One patient had 4, without change in exam or MRI. Two other patients had 2 relapses each, with new features and MRI lesions. The annualised relapse rate declined to 0.4 (from 2.9), an 86% ARR reduction. The mean EDSS declined from BL=3.05, to Y1=2.25, and Y2=2.22. Seven patients had confirmed disability improvement, 2 unchanged, 1 confirmed disability worsening. That patient had cord relapses with pial spinal cord enhancement and cerebral Gd+ lesions unchanged over 2 years suggesting a non-MS disease such as sarcoid.
On completion, mean MRI-T2-hyperintense lesion volume increased 3.6% BL-Y1, then declined -3.1% Y1 - Y2. Atrophy (SIENA): average -0.97% (SD 0.68%) brain atrophy BL-Y1 and -0.29% (SD 0.53%) Y1-Y2. Both suggest a contribution of active disease and subsequent pseudoatrophy in the first year with brain volume changes approximately normal in the second year. The mean Gd lesion number at entry was 9.2 (0-26), Y1 1.9 (0-13), Y2 0.11 (0-1). Conversion of enhancing lesions to T1-black holes: 4 patients at BL (n lesions = 1,1,2,2), no Y1 Gd lesions converted to black holes.
Conclusions: Alemtuzumab is a highly effective treatment for MS, even in a highly active cohort with considerably more pre-treatment than patients in the pivotal trials. Careful review of the diagnosis is needed in atypical cases before alemtuzumab treatment. Marked improvement in relapse rates, new Gd lesions, and second year brain atrophy occurred.
Disclosure:
Acknowledgments:
The authors wish particularly to acknowledge the substantial intellectual contributions, study design inputs, procedural support over the course of the study and reviews by Richard Worrell, B. Pharm. Mr Worrell is an employee of Sanofi-Aventis Australia Pty Ltd. We also wish to acknowledge significant contributions to study design and implementation by Jamshed Ahmed. Dr Ahmed was an employee of Sanofi-Aventis Australia Pty Ltd.
Disclosures
Sanofi-Aventis Australia Pty Ltd provided funding and product for this study. This company was not involved in the design, collection, analysis or interpretation of the study, but they were given the opportunity to review this abstract prior to submission. The decision to submit for publication was made by the authors independently.
S. Reddel has received payments for grant support from Biogen, CSL, Novartis and Sanofi-Genzyme, travel support from Merck, Sanofi-Genzyme and Teva, membership on advisory councils from Biogen, Merck, Sanofi-Genzyme and Teva, speaker's bureau from Biogen, Novartis, and Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.
S. Riminton has received payments for grant support from Octapharma and CSL Bioplasma, travel support from Sanofi-Genzyme, membership on advisory councils from Merck, Sanofi-Genzyme, National Blood Authority of Australia and Baxter Healthcare, speaker's bureau from Sanofi-Genzyme, and Biogen, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
T. Dugal has received travel support from Sanofi-Genzyme, and is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
D. Gahan is a shareholder in Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
F. Fitzgerald is an employee of Medical Safety Systems P/L Australia, owner of the RiskMx™ system.
K. Buzzard has received educational support from Sanofi-Genzyme, Teva and Biogen, speakers honorarium from Biogen, Novartis and Sanofi-Genzyme, and membership on advisory boards from Merck.
D. Erickson reports no disclosures