"Risk-benefit assessment of glatiramer acetate in multiple
sclerosis"
Ziemssen T, Neuhaus O, Hohlfeld R.
Department of Neuroimmunology, Max Planck Institute of Neurobiology,
Martinsried, Germany.
Glatiramer acetate, formerly known as
copolymer 1, is a mixture of synthetic polypeptides composed of four
amino acids. Glatiramer acetate has been shown to be effective in
preventing and suppressing experimental autoimmune encephalitis (EAE),
the animal model of multiple sclerosis (MS).
Therefore it was tested in several
clinical studies, where it was found to slow the progression of
disability and to reduce the relapse rate and the magnetic resonance
imaging (MRI)-defined disease activity and burden in
relapsing-remitting MS.
As a daily standard dose, 20mg of
glatiramer acetate is injected subcutaneously. After injection,
glatiramer acetate undergoes rapid degradation to amino acids and
shorter peptides; so it is not possible to measure any systemic
plasma concentrations or excretion rates.
Two major mechanisms have been proposed
to explain the effects of glatiramer acetate in EAE and MS: the
induction of glatiramer acetate-reactive T helper 2 (Th2)-like
regulatory suppressive cells and the interference with T cell
activation as an altered peptide ligand.
The most common adverse effects were
mild injection site reactions (erythema, inflammation and induration).
The most remarkable adverse event is the
acute and transient immediate postinjection reaction manifested by
flushing, chest tightness, palpitations and dyspnoea. Other reported
adverse effects are transient chest pain and lymphadenopathy.
Antibodies to glatiramer acetate induced
during treatment do not interfere with its clinical effects. In
several controlled clinical studies, glatiramer acetate has been
shown to provide consistent, reproducible clinical benefits in the
target population of patients with relapsing-remitting MS.
The safety profile and risk-benefit
ratio are excellent. Overall, glatiramer acetate is very well
tolerated and has an excellent risk-benefit profile in patients with
relapsing-remitting MS.
Drug Saf 2001;24(13):979-90
PMID: 11735654 [PubMed
link] |
