Contributions
Abstract: P895
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: The anti-CD52 humanized monoclonal antibody alemtuzumab is 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 the active comparator. Both CAMMS223 and CARE-MS I recruited treatment-naïve patients, while most of the patients recruited in CARE-MS II were at the first treatment failure. Therefore, the use of alemtuzumab in active MS patients who failed multiple disease-modifying treatments (DMTs) deserves further investigation.
Objective: To assess the two-year proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability regression after discontinuation of multiple DMTs because of lack of response or safety concerns.
Methods: In this longitudinal, observational study we prospectively collected clinical and magnetic resonance imaging (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 local regulatory agency. NEDA-3 wad defined as absence of relapses, disability worsening, and MRI activity. Disability regression was defined as a sustained reduction of ≥1-point in EDSS score.
Results: The study sample consists of 40 relapsing MS patients (33 women, 7 men) with mean age of 34 years, mean MS duration of 12 years, median number of relapses in the prior year of 2, and median EDSS score of 4.0 at the time of first alemtuzumab course. At baseline brain scan, 30 (72%) of them had gadolinium-enhancing lesions. The median number of previous DMTs was 4, including interferons, natalizumab, fingolimod, glatiramer acetate, mitoxantrone, cyclophosphamide, dimethylfumarate, rituximab, autologous hematopoietic stem cells transplantation. At two-year follow-up, 20 (50%) patients achieved NEDA-3, 32 (80%) were relapse-free, 37 (92.5%) were disability worsening-free, and 26 (65%) were MRI activity-free. Fourteen (35%) patients had a sustained disability regression. We found no predictor for the NEDA-3 status, while a greater number of baseline relapses was associated with higher chance of disability regression (odds ratio 2.4, p=0.015).
Discussion: Alemtuzumab promoted short-term clinical and MRI disease remission in 50% and disability regression in 35% of very active MS patients experiencing multiple DMT failures.
Disclosure: LP: speaker honoraria from Almirall, Biogen, Genzyme, Novartis, Roche and Teva; consulting fees from Biogen, Genzyme and Novartis; research grant from Genzyme and Italian MS Society. PA: consulting and/or lecture fees from Mylan, Roche, Almirall e Merck, Biogen, Genzyme, Novartis and Teva. SR: invited speaker, advisory boards, travel expenses from Merck Serono, Teva, Novartis, Biogen, and Genzyme. LB: travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva. MCB: advisory board membership and honoraria for speaking from Teva, Novartis, Sanofi, Merck Serono and Biogen. AG: speaker and consulting fees from Biogen, Sanofi-Genzyme, Merck Seronoand Teva. MM: honoraria from: Biogen, Novartis, Almirall, Teva. LM: speaking honoraria and/or consultant fees from Biogen, Merck Serono, Sanofi-Aventis, Teva, Novartis LM: speaking honoraria and/or consultant fees from Biogen, Genzyme and Teva. PP: speaking honoraria and/or consultant fees from Biogen, Merck serono, Teva, Novartis and Genzyme.CA: speaking honoraria and/or consultant fees from Merck Serono, Novartis, Genzyme. VB: speaking honoraria and/or consultant fees from Biogen Idec, Merck Serono, Bayer, Sanofi- Genzyme, Novartis. AB: nothing to disclose. DF: scientific advisory board and speaker honoraria from Merck Serono, Biogen, Sanofi-Genzyme, Bayer Shering and Novartis. EF: nothing to disclose. AF: research funding and lecture fees from Sanofi-Aventis, Biogen Idec, Merck Serono and Novartis. FG: scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis; funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall. LMEG: scientific advisory board for Merck Serono; funding for travel or speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Bayer Schering 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: lecturing honoraria from Biogen-Dompé, Biogen Idec and Novartis; funding for travel from Bayer-Schering, Novartis, Biogen-Dompé, Biogen Idec, Merck Serono, and Sanofi Genzyme. GL: scientific advisory boards for Almirall, Novartis, Biogen Idec, Sanofi-Aventis, Genzyme and Bayer Schering; funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis; research support from Novartis, 'Fondazione C. Serono', Biogen Idec, Bayer Schering and Sanofi-Aventis. FP: scientific advisory board for Almirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Roche and TEVA; fees for speaking activities by 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: P895
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: The anti-CD52 humanized monoclonal antibody alemtuzumab is 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 the active comparator. Both CAMMS223 and CARE-MS I recruited treatment-naïve patients, while most of the patients recruited in CARE-MS II were at the first treatment failure. Therefore, the use of alemtuzumab in active MS patients who failed multiple disease-modifying treatments (DMTs) deserves further investigation.
Objective: To assess the two-year proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability regression after discontinuation of multiple DMTs because of lack of response or safety concerns.
Methods: In this longitudinal, observational study we prospectively collected clinical and magnetic resonance imaging (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 local regulatory agency. NEDA-3 wad defined as absence of relapses, disability worsening, and MRI activity. Disability regression was defined as a sustained reduction of ≥1-point in EDSS score.
Results: The study sample consists of 40 relapsing MS patients (33 women, 7 men) with mean age of 34 years, mean MS duration of 12 years, median number of relapses in the prior year of 2, and median EDSS score of 4.0 at the time of first alemtuzumab course. At baseline brain scan, 30 (72%) of them had gadolinium-enhancing lesions. The median number of previous DMTs was 4, including interferons, natalizumab, fingolimod, glatiramer acetate, mitoxantrone, cyclophosphamide, dimethylfumarate, rituximab, autologous hematopoietic stem cells transplantation. At two-year follow-up, 20 (50%) patients achieved NEDA-3, 32 (80%) were relapse-free, 37 (92.5%) were disability worsening-free, and 26 (65%) were MRI activity-free. Fourteen (35%) patients had a sustained disability regression. We found no predictor for the NEDA-3 status, while a greater number of baseline relapses was associated with higher chance of disability regression (odds ratio 2.4, p=0.015).
Discussion: Alemtuzumab promoted short-term clinical and MRI disease remission in 50% and disability regression in 35% of very active MS patients experiencing multiple DMT failures.
Disclosure: LP: speaker honoraria from Almirall, Biogen, Genzyme, Novartis, Roche and Teva; consulting fees from Biogen, Genzyme and Novartis; research grant from Genzyme and Italian MS Society. PA: consulting and/or lecture fees from Mylan, Roche, Almirall e Merck, Biogen, Genzyme, Novartis and Teva. SR: invited speaker, advisory boards, travel expenses from Merck Serono, Teva, Novartis, Biogen, and Genzyme. LB: travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva. MCB: advisory board membership and honoraria for speaking from Teva, Novartis, Sanofi, Merck Serono and Biogen. AG: speaker and consulting fees from Biogen, Sanofi-Genzyme, Merck Seronoand Teva. MM: honoraria from: Biogen, Novartis, Almirall, Teva. LM: speaking honoraria and/or consultant fees from Biogen, Merck Serono, Sanofi-Aventis, Teva, Novartis LM: speaking honoraria and/or consultant fees from Biogen, Genzyme and Teva. PP: speaking honoraria and/or consultant fees from Biogen, Merck serono, Teva, Novartis and Genzyme.CA: speaking honoraria and/or consultant fees from Merck Serono, Novartis, Genzyme. VB: speaking honoraria and/or consultant fees from Biogen Idec, Merck Serono, Bayer, Sanofi- Genzyme, Novartis. AB: nothing to disclose. DF: scientific advisory board and speaker honoraria from Merck Serono, Biogen, Sanofi-Genzyme, Bayer Shering and Novartis. EF: nothing to disclose. AF: research funding and lecture fees from Sanofi-Aventis, Biogen Idec, Merck Serono and Novartis. FG: scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis; funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall. LMEG: scientific advisory board for Merck Serono; funding for travel or speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis, Bayer Schering 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: lecturing honoraria from Biogen-Dompé, Biogen Idec and Novartis; funding for travel from Bayer-Schering, Novartis, Biogen-Dompé, Biogen Idec, Merck Serono, and Sanofi Genzyme. GL: scientific advisory boards for Almirall, Novartis, Biogen Idec, Sanofi-Aventis, Genzyme and Bayer Schering; funding for travel and speaker honoraria from Sanofi-Aventis, Biogen Idec, Bayer Schering, Teva Neurosciences, Almirall, Genzyme and Novartis; research support from Novartis, 'Fondazione C. Serono', Biogen Idec, Bayer Schering and Sanofi-Aventis. FP: scientific advisory board for Almirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Roche and TEVA; fees for speaking activities by 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.