Contributions
Abstract: P1195
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Delaying disease progression from RRMS to SPMS is a key treatment goal in MS. In an MSBase cohort (17,356 MS patients [pts]; median baseline [BL] disease duration: 3.8 years [y]), 18% of pts converted to SPMS over median 5.8-y follow-up period using an SPMS definition based on EDSS scores and relapses (Lorscheider et al [Brain 2016;139:2395-405]). In alemtuzumab clinical trial pts with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had inadequate response
(≥1 relapse) to prior therapy (CARE-MS II; NCT00548405), relapse rates were low and EDSS scores were stable/improved over 6 y, without continuous treatment (extension study: NCT00930553).
Goal: Determine the conversion rate from RRMS to SPMS through 6 y among CARE-MS alemtuzumab-treated pts.
Methods: In CARE-MS I and II, pts received 2 alemtuzumab 12-mg courses (BL: 5 consecutive days;
12 months later: 3 consecutive days), and in the extension, as-needed alemtuzumab for relapse or MRI activity or another DMT per investigator discretion. Lorscheider's conversion to SPMS definition: disability progression in absence of relapse, worsening by 1 EDSS point in pts with EDSS ≤5.5 or 0.5 EDSS points in pts with EDSS ≥6, confirmed over ≥3 months within the leading Functional System (FS), in pts with EDSS score ≥4 and pyramidal FS score ≥2. Sensitivity analyses evaluated different confirmation periods and/or a minimum EDSS of 3.
Results: BL median disease duration in CARE-MS I and II was 1.7 and 3.8 y (2.8 pooled). 1.1% and 3.7% of alemtuzumab-treated CARE-MS I and II pts, respectively, converted to SPMS through 6 y
(2.5% pooled). Sensitivity analyses confirmed low conversion rates; using the same EDSS score (≥4) with longer progression confirmation periods, conversion rates were: CARE-MS I, 0.8%; CARE-MS II, 2.1%; pooled, 1.5% (6 months), 0.3%; 1.4%; 0.9% (12 months), or 0% (24 months). Conversion rates using a lower EDSS score (≥3) were also low (12 months: 1.3%, 3.7%, 2.6%; 24 months: 0%, 0.7%, 0.4%). 93% and 88% of alemtuzumab-treated pts who completed CARE-MS I and II and entered the extension remained on study through Y6; 63% and 50% received no additional treatment
(alemtuzumab or other DMT).
Conclusion: Low proportions of CARE-MS alemtuzumab-treated pts progressed to SPMS according to criteria developed by Lorscheider. Results of the primary analysis were confirmed by additional sensitivity analyses. Further confirmation of results in real-world cohorts is needed.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DH: Consulting fees/speaker honoraria (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
ABoster: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi Genzyme, and Teva).
ABertolotto: Advisory boards and/or speaker honoraria (Almirall, Bayer, Biogen, Novartis, Sanofi Genzyme, and Teva); grant support (Almirall, Associazione San Luigi Gonzaga ONLUS, Bayer, Biogen, Fondazione per la Ricerca Biomedica ONLUS, Merck, Novartis, Sanofi Genzyme, Teva, and the Italian Multiple Sclerosis Society).
MF: Honoraria/consulting fees (Actelion, Bayer, Biogen, Canada Innovation, Chugai, EMD Canada, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva); member of advisory board, board of directors, or other similar group (Actelion, Bayer, Biogen, Merck Serono, Novartis, Opexa, Roche, and Sanofi-Aventis); participation in speaker's bureau (Sanofi Genzyme).
SG, IF, SC, KT, DHM: Compensation as employees of Sanofi.
TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); grant/research support (Biogen, Novartis, Sanofi Genzyme, and Teva).
Abstract: P1195
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Delaying disease progression from RRMS to SPMS is a key treatment goal in MS. In an MSBase cohort (17,356 MS patients [pts]; median baseline [BL] disease duration: 3.8 years [y]), 18% of pts converted to SPMS over median 5.8-y follow-up period using an SPMS definition based on EDSS scores and relapses (Lorscheider et al [Brain 2016;139:2395-405]). In alemtuzumab clinical trial pts with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or had inadequate response
(≥1 relapse) to prior therapy (CARE-MS II; NCT00548405), relapse rates were low and EDSS scores were stable/improved over 6 y, without continuous treatment (extension study: NCT00930553).
Goal: Determine the conversion rate from RRMS to SPMS through 6 y among CARE-MS alemtuzumab-treated pts.
Methods: In CARE-MS I and II, pts received 2 alemtuzumab 12-mg courses (BL: 5 consecutive days;
12 months later: 3 consecutive days), and in the extension, as-needed alemtuzumab for relapse or MRI activity or another DMT per investigator discretion. Lorscheider's conversion to SPMS definition: disability progression in absence of relapse, worsening by 1 EDSS point in pts with EDSS ≤5.5 or 0.5 EDSS points in pts with EDSS ≥6, confirmed over ≥3 months within the leading Functional System (FS), in pts with EDSS score ≥4 and pyramidal FS score ≥2. Sensitivity analyses evaluated different confirmation periods and/or a minimum EDSS of 3.
Results: BL median disease duration in CARE-MS I and II was 1.7 and 3.8 y (2.8 pooled). 1.1% and 3.7% of alemtuzumab-treated CARE-MS I and II pts, respectively, converted to SPMS through 6 y
(2.5% pooled). Sensitivity analyses confirmed low conversion rates; using the same EDSS score (≥4) with longer progression confirmation periods, conversion rates were: CARE-MS I, 0.8%; CARE-MS II, 2.1%; pooled, 1.5% (6 months), 0.3%; 1.4%; 0.9% (12 months), or 0% (24 months). Conversion rates using a lower EDSS score (≥3) were also low (12 months: 1.3%, 3.7%, 2.6%; 24 months: 0%, 0.7%, 0.4%). 93% and 88% of alemtuzumab-treated pts who completed CARE-MS I and II and entered the extension remained on study through Y6; 63% and 50% received no additional treatment
(alemtuzumab or other DMT).
Conclusion: Low proportions of CARE-MS alemtuzumab-treated pts progressed to SPMS according to criteria developed by Lorscheider. Results of the primary analysis were confirmed by additional sensitivity analyses. Further confirmation of results in real-world cohorts is needed.
Study support: Sanofi and Bayer HealthCare Pharmaceuticals.
Disclosure:
DH: Consulting fees/speaker honoraria (Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Teva).
ABoster: Consulting fees and/or fees for non-CME services (Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi Genzyme, and Teva).
ABertolotto: Advisory boards and/or speaker honoraria (Almirall, Bayer, Biogen, Novartis, Sanofi Genzyme, and Teva); grant support (Almirall, Associazione San Luigi Gonzaga ONLUS, Bayer, Biogen, Fondazione per la Ricerca Biomedica ONLUS, Merck, Novartis, Sanofi Genzyme, Teva, and the Italian Multiple Sclerosis Society).
MF: Honoraria/consulting fees (Actelion, Bayer, Biogen, Canada Innovation, Chugai, EMD Canada, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva); member of advisory board, board of directors, or other similar group (Actelion, Bayer, Biogen, Merck Serono, Novartis, Opexa, Roche, and Sanofi-Aventis); participation in speaker's bureau (Sanofi Genzyme).
SG, IF, SC, KT, DHM: Compensation as employees of Sanofi.
TZ: Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva); grant/research support (Biogen, Novartis, Sanofi Genzyme, and Teva).