Therapeutic decisions in multiple sclerosis: moving beyond efficacy.
Several innovative disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis have been licensed recently or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least 1 of 4 properties, namely (1) trafficking, (2) survival, (3) function, or (4) proliferation. In contrast to β-interferons and glatiramer acetate, the first-generation DMTs, several newer therapies are imbued with safety issues, which may be attributed to their structure or metabolism. In addition to efficacy, understanding the relationship between the mechanism of action of the DMTs and their safety profile is pertinent for decision making and patient care. In this article, we focus primarily on the safety of DMTs in the context of understanding their pharmacological characteristics, including molecular targets, mechanism of action, chemical structure, and metabolism. While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients and to ensure future therapies have the most advantageous benefit-risk profiles. Recognizing the individual classes of DMTs described here may be valuable when considering use of such agents sequentially or possibly in combination.
Wolfgang
W
Brück
Raff
R
Gold
Brett T
BT
Lund
Celia
C
Oreja-Guevara
Alexandre
A
Prat
Collin M
CM
Spencer
Lawrence
L
Steinman
Mar
M
Tintoré
Timothy L
TL
Vollmer
Martin S
MS
Weber
Leslie P
LP
Weiner
Tjalf
T
Ziemssen
Scott S
SS
Zamvil
D006801:Humans; D007107:Immune System / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D036302:Therapeutic Human Experimentation
D007155:Immunologic Factors