PMID- 29081658
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1176-6336 (Print)
IS  - 1178-203X (Electronic)
IS  - 1176-6336 (Linking)
VI  - 13
DP  - 2017
TI  - Understanding the positive benefit:risk profile of alemtuzumab in relapsing 
      multiple sclerosis: perspectives from the Alemtuzumab Clinical Development 
      Program.
PG  - 1423-1437
LID - 10.2147/TCRM.S143509 [doi]
AB  - The introduction of high-efficacy therapies for relapsing-remitting multiple 
      sclerosis has driven re-evaluation of treatment goals and benefit:risk 
      considerations in treatment choice. In the alemtuzumab Phase II and III clinical 
      trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon 
      beta-1a demonstrated significantly reduced annualized relapse rates and improved 
      magnetic resonance imaging outcomes, and were significantly more likely to 
      achieve no evidence of disease activity and reduction in brain volume loss. In 
      two of the studies, alemtuzumab-treated patients had a significantly reduced risk 
      of 6-month confirmed disease worsening, compared with subcutaneous interferon 
      beta-1a. Benefits were maintained throughout 5 years, with a majority of patients 
      receiving no alemtuzumab retreatment or other disease-modifying therapy. Trial 
      results support alemtuzumab's manageable, consistent safety profile in 
      relapsing-remitting multiple sclerosis. Infusion-associated reactions, the most 
      frequent adverse events (AEs), can be minimized by corticosteroid pretreatment, 
      monitoring, and symptomatic management. Other AEs include infections and 
      autoimmune events. Oral anti-herpes prophylaxis should be initiated on the first 
      day of each alemtuzumab treatment course and continued according to local 
      guidelines. Overall cancer risk was lower in the alemtuzumab clinical trials than 
      in a reference population; however, continuing surveillance will determine if 
      alemtuzumab may be associated with certain malignancies such as thyroid papillary 
      carcinoma and melanoma, which are currently identified as potential risks. The 
      post-approval risk management strategy includes a safety monitoring program. 
      Autoimmune AEs (thyroid events, immune thrombocytopenia, nephropathies) can be 
      detected in a timely manner with the monitoring program, which includes physician 
      and patient education about the signs and symptoms, monthly renal and hematologic 
      monitoring, and quarterly thyroid function monitoring for 48 months after the 
      last alemtuzumab course. Education, vigilance by physicians and patients, and 
      monthly laboratory monitoring are recommended to maintain alemtuzumab's positive 
      benefit:risk profile.
FAU - Havrdova, Eva
AU  - Havrdova E
AD  - Department of Neurology and Center of Clinical Neuroscience, First Faculty of 
      Medicine, Charles University and General University Hospital in Prague, Prague, 
      Czech Republic.
FAU - Cohen, Jeffrey A
AU  - Cohen JA
AD  - Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
FAU - Horakova, Dana
AU  - Horakova D
AD  - Department of Neurology and Center of Clinical Neuroscience, First Faculty of 
      Medicine, Charles University and General University Hospital in Prague, Prague, 
      Czech Republic.
FAU - Kovarova, Ivana
AU  - Kovarova I
AD  - Department of Neurology and Center of Clinical Neuroscience, First Faculty of 
      Medicine, Charles University and General University Hospital in Prague, Prague, 
      Czech Republic.
FAU - Meluzinova, Eva
AU  - Meluzinova E
AD  - Department of Neurology, Second Faculty of Medicine, Charles University, Motol 
      University Hospital, Prague, Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20171016
PL  - New Zealand
TA  - Ther Clin Risk Manag
JT  - Therapeutics and clinical risk management
JID - 101253281
PMC - PMC5652900
OTO - NOTNLM
OT  - MRI outcomes
OT  - NEDA
OT  - alemtuzumab
OT  - annualized relapse rate
OT  - autoimmune event
OT  - infusion-associated reaction
OT  - multiple sclerosis
OT  - no evidence of disease activity
OT  - risk mitigation
COIS- Disclosure Editorial support was provided by Linda Wychowski, PhD, and Rosemary 
      Perkins, Envision Scientific Solutions. Funding for editorial support was 
      provided by Sanofi. This manuscript was reviewed for scientific and medical 
      accuracy by Darren P Baker, PhD, of Sanofi. JAC received personal compensation 
      for consulting for Adamas, Celgene, Mallinckrodt, Merck, and Novartis and as a 
      Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and 
      Clinical. EH received honoraria and grant support (Actelion, Biogen, Merck 
      Serono, Novartis, Receptos, Roche, Sanofi, and Teva), and support from the Czech 
      Ministry of Education research project Progres Q27/LF1. DH received speaker 
      honoraria and consultant fees (Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and 
      Teva), financial support for research activities (Biogen), and support from the 
      Czech Ministry of Education project Progres Q27/LF1. IK received speaker 
      honoraria and consultant fees (Bayer, Biogen, Merck Serono, Novartis, and Teva), 
      and financial support for research activities (Biogen). EM received speaker 
      honoraria and consultant fees (Biogen, Merck Serono, Novartis, Sanofi, and Teva). 
      The authors report no other conflicts of interest in this work.
EDAT- 2017/10/31 06:00
MHDA- 2017/10/31 06:01
PMCR- 2017/10/16
CRDT- 2017/10/31 06:00
PHST- 2017/10/31 06:00 [entrez]
PHST- 2017/10/31 06:00 [pubmed]
PHST- 2017/10/31 06:01 [medline]
PHST- 2017/10/16 00:00 [pmc-release]
AID - tcrm-13-1423 [pii]
AID - 10.2147/TCRM.S143509 [doi]
PST - epublish
SO  - Ther Clin Risk Manag. 2017 Oct 16;13:1423-1437. doi: 10.2147/TCRM.S143509. 
      eCollection 2017.