PMID- 35855752
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220812
IS  - 1176-6336 (Print)
IS  - 1178-203X (Electronic)
IS  - 1176-6336 (Linking)
VI  - 18
DP  - 2022
TI  - Practical Management for Use of Eculizumab in the Treatment of Severe, 
      Refractory, Non-Thymomatous, AChR + Generalized Myasthenia Gravis: A Systematic 
      Review.
PG  - 699-719
LID - 10.2147/TCRM.S266031 [doi]
AB  - Myasthenia gravis (MG) is a rare autoimmune disorder caused by specific 
      autoantibodies at the neuromuscular junction. MG is classified by the antigen 
      specificity of these antibodies. Acetylcholine receptor (AChR) antibodies are the 
      most common type (74-88%), followed by anti-muscle specific kinase (MuSK) and 
      other antibodies. While all these antibodies lead to neuromuscular transmission 
      failure, the immuno-pathogenic mechanisms are distinct. Complement activation is 
      a primary driver of AChR antibody-positive MG (AChR+ MG) pathogenesis. This leads 
      to the formation of the membrane attack complex and destruction of AChR receptors 
      and the postsynaptic membrane resulting in impaired neurotransmission and muscle 
      weakness characteristic of MG. Broad-based immune-suppressants like 
      corticosteroids are effective in controlling MG; however, their long-term use can 
      be associated with significant adverse effects. Advances in translational 
      research have led to the development of more directed therapeutic agents that are 
      likely to alter the future of MG treatment. Eculizumab is a humanized monoclonal 
      antibody that inhibits the cleavage of complement protein C5 and is approved for 
      use in generalized MG. In this review, we discuss the pathophysiology of MG; the 
      therapeutic efficacy and tolerability of eculizumab, as well as the practical 
      guidelines for its use in MG; future studies exploring the role of eculizumab in 
      different stages and subtypes of MG subtypes; the optimal duration of therapy and 
      its discontinuation; the characterization of non-responder patients; and the use 
      of biomarkers for monitoring therapy are highlighted. Based on the 
      pathophysiologic mechanisms, emerging therapies and new therapeutic targets are 
      also reviewed.
CI  - (c) 2022 Waheed et al.
FAU - Waheed, Waqar
AU  - Waheed W
AUID- ORCID: 0000-0003-3049-5430
AD  - Department of Neurological Sciences, The University of Vermont and the University 
      of Vermont Medical Center, Burlington, VT, USA.
FAU - Newman, Eric
AU  - Newman E
AD  - Department of Neurological Sciences, The University of Vermont and the University 
      of Vermont Medical Center, Burlington, VT, USA.
FAU - Aboukhatwa, Marwa
AU  - Aboukhatwa M
AUID- ORCID: 0000-0003-3826-1620
AD  - Pharmacotherapy Department, University of Vermont Medical Center, Burlington, VT, 
      USA.
FAU - Moin, Maryam
AU  - Moin M
AD  - Department of Neurology, University of Illinois College of Medicine, Peoria, IL, 
      USA.
FAU - Tandan, Rup
AU  - Tandan R
AD  - Department of Neurological Sciences, The University of Vermont and the University 
      of Vermont Medical Center, Burlington, VT, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220712
PL  - New Zealand
TA  - Ther Clin Risk Manag
JT  - Therapeutics and clinical risk management
JID - 101253281
EIN - Ther Clin Risk Manag. 2022 Aug 03;18:773-774. PMID: 35958346
PMC - PMC9288180
OTO - NOTNLM
OT  - autoantibodies
OT  - complement
OT  - eculizumab
OT  - myasthenia gravis
OT  - pathophysiology
COIS- Professor Rup Tandan reports grants, personal fees from Alexion Pharmaceuticals, 
      during the conduct of the study. The authors report no other conflicts of 
      interest in this work.
EDAT- 2022/07/21 06:00
MHDA- 2022/07/21 06:01
PMCR- 2022/07/12
CRDT- 2022/07/20 04:04
PHST- 2022/04/02 00:00 [received]
PHST- 2022/07/04 00:00 [accepted]
PHST- 2022/07/20 04:04 [entrez]
PHST- 2022/07/21 06:00 [pubmed]
PHST- 2022/07/21 06:01 [medline]
PHST- 2022/07/12 00:00 [pmc-release]
AID - 266031 [pii]
AID - 10.2147/TCRM.S266031 [doi]
PST - epublish
SO  - Ther Clin Risk Manag. 2022 Jul 12;18:699-719. doi: 10.2147/TCRM.S266031. 
      eCollection 2022.