Contributions
Abstract: P614
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The anti-CD52 humanized monoclonal antibody alemtuzumab was recently approved for the treatment of active relapsing-remitting multiple sclerosis (MS), based on phase-2 (CAMMS223) and phase-3 clinical trials (CARE-MS I and CARE-MS II), where high-dose interferon beta-1a was used as active comparator. Both CAMMS223 and CARE-MS I recruited treatment-naïve patients with MS duration ≤3 and 5 years (respectively) and Expanded Disability Status Scale (EDSS) ≤3.0. By contrast, CARE-MS II recruited patients with MS duration ≤10 years, EDSS ≤5.0. and prior exposure to disease-modifying drugs (DMDs); however, about 3/4 of them did not respond to only one DMD. Therefore, the potential use of alemtuzumab in aggressive and treatment-refractory MS deserves further investigation.
Objective: To assess the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) - defined as no relapses, no disability worsening, and no magnetic resonance imaging (MRI) activity - after discontinuation of multiple DMDs because of lack of response or safety concerns.
Methods: In this longitudinal, observational study we are prospectively collecting clinical and MRI data of a real-world cohort of patients treated with alemtuzumab between May 2014 and June 2015 in 21 tertiary Italian MS Centres according to a “free-of-charge” protocol available before its approval by the Italian regulatory agency.
Results: The study sample consists of 40 patients (33 F, 7 M) with a mean age of 34 years, mean MS duration of 12 years, median number of relapses in the prior year of 2, and median EDSS of 4.0 at first alemtuzumab course. At baseline brain scan, 72% of them had gadolinium-enhancing lesions. The median number of previous DMDs was 4 (interferons: n=36; natalizumab: n=32; fingolimod: n=29; glatiramer acetate: n=19; mitoxantrone: n=12; cyclophosphamide: n=7; dimethylfumarate :n=3; rituximab: n=1; autologous hematopoietic stem cells transplantation: n=1). After a mean follow-up of 1.5 years, 25 (62%) patients maintained NEDA-3, 32 (80%) were relapse-free, 37 (92%) were disability worsening-free, and 26 (65%) were MRI activity-free. Infusion-related reactions were observed in 38 (95%) patients. At moment, 34 patients have received the second course.
Discussion: Alemtuzumab promoted short-term remission of the disease in aggressive MS patients, independently from previous exposures to multiple DMDs. Further data collection and elaboration are in progress.
Disclosure: This study was supported by Sanofi-Genzyme.
LP: speaker honoraria from Biogen, Genzyme, Novartis and Teva; consulting fees from Biogen and Novartis; research grant from Genzyme.
PA: consulting and/or lecture fees from Biogen Idec, Genzyme, Novartis and Teva.
LB: lecture fees from Merck Serono and Teva.
MCB: consulting and/or lecture fees from Biogen, Teva, Genzyme, Novartis.
AG: speaker and consulting fees from Biogen, Genzyme, Novartis and Teva.
MM: honoraria from Biogen, Novartis, Almirall, Teva
LM: speaking honoraria and/or consulting fees from Biogen, Bayer Schering Pharma, Merck Serono and Sanofi-Aventis.
LM: speaking honoraria and/or consultant fees from Biogen and Genzyme.
PP: speaking honoraria and/or consultant fees from Biogen, Merck Serono, Teva, Novartis and Genzyme.
CA: speaking honoraria and/or consulting fees from Merck Serono, Novartis, Genzyme.
MRR: honoraria from Biogen, Merck Serono, Teva, Genzyme, Novartis, Bayer Schering.
AB: honoriaria from Almirall, Genzyme, Novartis.
DF: nothing to disclose.
EF: nothing to disclose.
AF: research funding and lecture fees from Sanofi-Aventis, Biogen, Merck Serono and Novartis.
FG: consulting fees for Biogen, Novartis and Sanofi Aventis and speaker honoraria from Biogen, Merck Serono, and Almirall.
LG: scientific advisory board for Merck Serono, speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Bayer Schering Pharma and Solvay Pharmaceuticals, Inc.; institutional research support form Teva Pharmaceuticals Industries Ltd, Biogen, Genzyme Corporation, Sanofi-Aventis, Merck Serono, Novartis and Eisai Inc.; research support from Merck Serono, Biogen and Ministero della Salute of Italy.
AL: speaking honoraria from Biogen and Novartis
GL: scientific advisory boards from Almirall, Novartis, Biogen, Sanofi-Aventis, Genzyme and Bayer Schering; speaking honoraria from Sanofi-Aventis, Biogen, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis; research support from Novartis, "Fondazione C. Serono", Biogen, Bayer Schering and Sanofi-Aventis.
FP: consulting fees and speaking honoriaria from Almirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme and TEVA.
EP: personal fees and non-financial support from Biogen Idec, Merck Serono, Teva, Genzyme and Novartis.
AMR: nothing to disclose.
PS: nothing to disclose.
Abstract: P614
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The anti-CD52 humanized monoclonal antibody alemtuzumab was recently approved for the treatment of active relapsing-remitting multiple sclerosis (MS), based on phase-2 (CAMMS223) and phase-3 clinical trials (CARE-MS I and CARE-MS II), where high-dose interferon beta-1a was used as active comparator. Both CAMMS223 and CARE-MS I recruited treatment-naïve patients with MS duration ≤3 and 5 years (respectively) and Expanded Disability Status Scale (EDSS) ≤3.0. By contrast, CARE-MS II recruited patients with MS duration ≤10 years, EDSS ≤5.0. and prior exposure to disease-modifying drugs (DMDs); however, about 3/4 of them did not respond to only one DMD. Therefore, the potential use of alemtuzumab in aggressive and treatment-refractory MS deserves further investigation.
Objective: To assess the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) - defined as no relapses, no disability worsening, and no magnetic resonance imaging (MRI) activity - after discontinuation of multiple DMDs because of lack of response or safety concerns.
Methods: In this longitudinal, observational study we are prospectively collecting clinical and MRI data of a real-world cohort of patients treated with alemtuzumab between May 2014 and June 2015 in 21 tertiary Italian MS Centres according to a “free-of-charge” protocol available before its approval by the Italian regulatory agency.
Results: The study sample consists of 40 patients (33 F, 7 M) with a mean age of 34 years, mean MS duration of 12 years, median number of relapses in the prior year of 2, and median EDSS of 4.0 at first alemtuzumab course. At baseline brain scan, 72% of them had gadolinium-enhancing lesions. The median number of previous DMDs was 4 (interferons: n=36; natalizumab: n=32; fingolimod: n=29; glatiramer acetate: n=19; mitoxantrone: n=12; cyclophosphamide: n=7; dimethylfumarate :n=3; rituximab: n=1; autologous hematopoietic stem cells transplantation: n=1). After a mean follow-up of 1.5 years, 25 (62%) patients maintained NEDA-3, 32 (80%) were relapse-free, 37 (92%) were disability worsening-free, and 26 (65%) were MRI activity-free. Infusion-related reactions were observed in 38 (95%) patients. At moment, 34 patients have received the second course.
Discussion: Alemtuzumab promoted short-term remission of the disease in aggressive MS patients, independently from previous exposures to multiple DMDs. Further data collection and elaboration are in progress.
Disclosure: This study was supported by Sanofi-Genzyme.
LP: speaker honoraria from Biogen, Genzyme, Novartis and Teva; consulting fees from Biogen and Novartis; research grant from Genzyme.
PA: consulting and/or lecture fees from Biogen Idec, Genzyme, Novartis and Teva.
LB: lecture fees from Merck Serono and Teva.
MCB: consulting and/or lecture fees from Biogen, Teva, Genzyme, Novartis.
AG: speaker and consulting fees from Biogen, Genzyme, Novartis and Teva.
MM: honoraria from Biogen, Novartis, Almirall, Teva
LM: speaking honoraria and/or consulting fees from Biogen, Bayer Schering Pharma, Merck Serono and Sanofi-Aventis.
LM: speaking honoraria and/or consultant fees from Biogen and Genzyme.
PP: speaking honoraria and/or consultant fees from Biogen, Merck Serono, Teva, Novartis and Genzyme.
CA: speaking honoraria and/or consulting fees from Merck Serono, Novartis, Genzyme.
MRR: honoraria from Biogen, Merck Serono, Teva, Genzyme, Novartis, Bayer Schering.
AB: honoriaria from Almirall, Genzyme, Novartis.
DF: nothing to disclose.
EF: nothing to disclose.
AF: research funding and lecture fees from Sanofi-Aventis, Biogen, Merck Serono and Novartis.
FG: consulting fees for Biogen, Novartis and Sanofi Aventis and speaker honoraria from Biogen, Merck Serono, and Almirall.
LG: scientific advisory board for Merck Serono, speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Bayer Schering Pharma and Solvay Pharmaceuticals, Inc.; institutional research support form Teva Pharmaceuticals Industries Ltd, Biogen, Genzyme Corporation, Sanofi-Aventis, Merck Serono, Novartis and Eisai Inc.; research support from Merck Serono, Biogen and Ministero della Salute of Italy.
AL: speaking honoraria from Biogen and Novartis
GL: scientific advisory boards from Almirall, Novartis, Biogen, Sanofi-Aventis, Genzyme and Bayer Schering; speaking honoraria from Sanofi-Aventis, Biogen, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis; research support from Novartis, "Fondazione C. Serono", Biogen, Bayer Schering and Sanofi-Aventis.
FP: consulting fees and speaking honoriaria from Almirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme and TEVA.
EP: personal fees and non-financial support from Biogen Idec, Merck Serono, Teva, Genzyme and Novartis.
AMR: nothing to disclose.
PS: nothing to disclose.