TY - JOUR
T1 - Alemtuzumab outcomes by age
T2 - Post hoc analysis from the randomized CARE-MS studies over 8 years
AU - CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators
AU - Bass, Ann D.
AU - Arroyo, Rafael
AU - Boster, Aaron L.
AU - Boyko, Alexey N.
AU - Eichau, Sara
AU - Ionete, Carolina
AU - Limmroth, Volker
AU - Navas, Carlos
AU - Pelletier, Daniel
AU - Pozzilli, Carlo
AU - Ravenscroft, Jennifer
AU - Sousa, Livia
AU - Tintoré, Mar
AU - Uitdehaag, Bernard M.J.
AU - Baker, Darren P.
AU - Daizadeh, Nadia
AU - Choudhry, Zia
AU - Rog, David
N1 - Funding Information: The study was supported by Sanofi and Bayer HealthCare Pharmaceuticals . Funding Information: Dr Bass reports receiving research funding, compensation for medical advisory boards, and compensation for speaker's bureaus from Actelion, Biogen, EMD Serono, Genentech-Roche, Mallinckrodt, Novartis, Sanofi, and TG Therapeutics. Dr Arroyo reports being an advisory board participant and receiving speaking fees from Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva. Dr Boster reports receiving consulting fees and/or fees for non-CME services from Biogen, Mallinckrodt, Medtronic, Novartis, Sanofi, and Teva. Prof Boyko reports receiving consulting fees and/or participating in clinical trials for Actelion, Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva, and TG Therapeutics. Prof Eichau reports receiving consulting and/or speaking fees from Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva. Prof Ionete reports receiving compensation for advisory board participation for Sanofi, and research support from Biogen, Roche, and Sanofi. Prof Limmroth reports receiving honoraria for consulting and speaking at symposia for Bayer, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva, with approval by the HR Department, Cologne General Hospital, and University of Cologne. Prof Navas reports receiving consulting and speaking fees from Bayer-Schering Pharma, Genzyme, Merck Serono, Novartis, Roche, and Stendhal, along with research support from Merck Serono, Novartis, and Roche. Dr Pelletier reports receiving consulting and/or speaking fees, along with grant and/or research support, from Biogen, Merck Serono, Novartis, Roche, and Sanofi. Prof Pozzilli reports receiving consulting and/or speaking fees, research, and travel grants from Actelion, Biogen, Merck, Novartis, Sanofi, and Teva. Ms Ravenscroft reports receiving consulting fees for non-CME services from Acorda, Biogen, Mallinckrodt, and Sanofi; employee of Sanofi as of March 2019. Prof Sousa reports receiving compensation for advisory board participation and speaking fees from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Roche, and Teva. Prof Tintoré reports receiving speaking honoraria and travel expenses for scientific meetings from Almirall, Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis, and Teva. Dr Uitdehaag reports receiving consulting fees from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva. Dr Baker and Dr Daizadeh report being employees of Sanofi. Dr Choudhry reports receiving personal compensation as an employee of Sanofi during study conduct and analysis. Dr Rog reports receiving consulting fees from Bayer Schering, Biogen, Celgene, MedDay, Merck Serono, Novartis, Roche, Sanofi, and Teva Neuroscience, along with research support from Actelion, Biogen, GW Pharma, Merck Serono, Mitsubishi, Novartis, Sanofi, Teva Neuroscience, and TG Therapeutics. Funding Information: The authors and Sanofi thank the patients for their participation in the trials, as well as the CARE-MS Steering Committee, and CAMMS03409 and TOPAZ investigators. Critical review of the manuscript was provided by Ericka M. Bueno, PhD, and Colin Mitchell, PhD, of Sanofi. Editorial assistance was provided by Rebecca L. Orndorff, PhD, and Valerie P. Zediak, PhD, of Eloquent Scientific Solutions, and was funded by Sanofi. The CARE-MS trials and their extension study, as well as the TOPAZ study, were sponsored by Sanofi and Bayer HealthCare Pharmaceuticals. Publisher Copyright: © 2020
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Background: Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]). Methods: Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years). Results: Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22–0.24 vs. 0.38–0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%–92% vs. 62%–88%; achievement of 6-month confirmed disability improvement [CDI]: 20%–31% vs. 13%–25%), increased proportions free of MRI disease activity (70%–86% vs. 42%–63% per year), and slowed brain volume loss (BVL; –0.45% to –0.87% vs. –0.50% to –1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%–2.2% vs. >45 years: 8.1%) and deaths (0%–1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts. Conclusions: Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.
AB - Background: Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]). Methods: Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years). Results: Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22–0.24 vs. 0.38–0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%–92% vs. 62%–88%; achievement of 6-month confirmed disability improvement [CDI]: 20%–31% vs. 13%–25%), increased proportions free of MRI disease activity (70%–86% vs. 42%–63% per year), and slowed brain volume loss (BVL; –0.45% to –0.87% vs. –0.50% to –1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%–2.2% vs. >45 years: 8.1%) and deaths (0%–1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts. Conclusions: Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.
KW - Age
KW - Alemtuzumab
KW - Efficacy
KW - Long-term
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85099636941&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.msard.2020.102717
DO - https://doi.org/10.1016/j.msard.2020.102717
M3 - Article
C2 - 33476880
SN - 2211-0348
VL - 49
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
M1 - 102717
ER -