TY - JOUR
T1 - Moving toward earlier treatment of multiple sclerosis
T2 - Findings from a decade of clinical trials and implications for clinical practice
AU - Freedman, Mark S.
AU - Comi, Giancarlo
AU - De Stefano, Nicola
AU - Barkhof, Frederik
AU - Polman, Chris H.
AU - Uitdehaag, Bernard M J
AU - Lehr, Lorenz
AU - Stubinski, Bettina
AU - Kappos, Ludwig
PY - 2014/3
Y1 - 2014/3
N2 - The first clinical presentation of multiple sclerosis (MS) is usually a single episode of typical symptoms and signs and is designated a "first clinical demyelinating event" (FCDE) or a "clinically isolated syndrome". Patients with an FCDE who show 'silent' magnetic resonance imaging lesions are at high risk of further clinical events and therefore of meeting the criteria for the diagnosis of clinically definite MS (CDMS). Here we review five Phase III trials, in which treatment with the following disease-modifying drugs (DMDs) was initiated at this early stage: interferon beta (ETOMS, CHAMPS, BENEFIT, and REFLEX) and glatiramer acetate (PreCISe). Differences in the design of the trials and their patient inclusion criteria limit comparisons. However, the proportion of placebo-treated patients who developed CDMS within 2 years was 38-45% across studies, and this rate was significantly reduced by DMD treatment. Conversion to McDonald MS was reported by only two of the trials: BENEFIT (2001 criteria) and REFLEX (2005 criteria). Around 85% of placebo-treated patients developed McDonald MS by 2 years in each, and again a beneficial effect of DMD treatment was seen. Overall, these studies support early use of DMDs to treat patients with an FCDE who are at high risk of conversion to CDMS.
AB - The first clinical presentation of multiple sclerosis (MS) is usually a single episode of typical symptoms and signs and is designated a "first clinical demyelinating event" (FCDE) or a "clinically isolated syndrome". Patients with an FCDE who show 'silent' magnetic resonance imaging lesions are at high risk of further clinical events and therefore of meeting the criteria for the diagnosis of clinically definite MS (CDMS). Here we review five Phase III trials, in which treatment with the following disease-modifying drugs (DMDs) was initiated at this early stage: interferon beta (ETOMS, CHAMPS, BENEFIT, and REFLEX) and glatiramer acetate (PreCISe). Differences in the design of the trials and their patient inclusion criteria limit comparisons. However, the proportion of placebo-treated patients who developed CDMS within 2 years was 38-45% across studies, and this rate was significantly reduced by DMD treatment. Conversion to McDonald MS was reported by only two of the trials: BENEFIT (2001 criteria) and REFLEX (2005 criteria). Around 85% of placebo-treated patients developed McDonald MS by 2 years in each, and again a beneficial effect of DMD treatment was seen. Overall, these studies support early use of DMDs to treat patients with an FCDE who are at high risk of conversion to CDMS.
KW - Clinically isolated syndrome
KW - Disease-modifying drug
KW - First clinical demyelinating event
KW - Glatiramer acetate
KW - Interferon beta
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84892812696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892812696&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2013.07.001
DO - 10.1016/j.msard.2013.07.001
M3 - Article
AN - SCOPUS:84892812696
VL - 3
SP - 147
EP - 155
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
IS - 2
ER -