October 17, 2007 (Prague, Czech Republic) -- A
long-term follow-up analysis of the pivotal North
American interferon beta-1b (IFNB-1b; Betaferon®)
trial shows that results on the Expanded
Disability Status Scale (EDSS) and measures of
magnetic resonance imaging (MRI) burden of disease
in patients with MS can reliably predict cognitive
status up to 16 years later. These findings were
presented here at the 23rd Congress of the
European Committee for the Treatment and Research
in Multiple Sclerosis on October 14th
in a late-breaking session.
Longest Follow-up
“We are quite excited about these results, and
believe they make a significant contribution to
our understanding of the relationships between
early disease severity and long-term cognitive
outcome. This is the longest follow-up study to
date, and the only study with such a comprehensive
battery of cognitive testing,” senior study author
Anthony Traboulsee, MD[?] clinical neurologist at
the University of British Columbia, Vancouver, BC,
Canada.
Dr.
Traboulsee’s team performed a multi-center
observational study that collected cross-sectional
data from patients with relapsing-remitting MS who
participated in the North American interferon
beta-1b (IFNB-1b; Betaferon®) trial.
179 patients (mean age 51.4 years, standard
deviation 7.2, median EDSS 4.5) were given a
battery of cognitive assessment tools: Paced
Auditory Serial Addition Task (PASAT), Symbol
Digit Modality Task (SDMT), California Verbal
Learning Test–II (CVLT-II), Controlled Oral Word
Association task (COWAT), Delis-Kaplan Executive
Function System (D-KEFS), and the Wechsler Test of
Adult Reading (WTAR), to provide an estimate of
pre-morbid IQ. Additionally, scores on five tests
of current cognitive function were combined to
produce a Cognitive Performance Index (CPI).
The
researchers calculated the correlations between
the current cognitive data and the prospectively
collected EDSS and MRI variables from the IFNB-1b;
Betaferon® trial 16 years earlier.
Strong and
Significant Relation
An
analysis of the data revealed a strong and
significant relation between all cognitive test
scores at 16 years and both baseline EDSS and
baseline MRI T2 burden of disease. Pearson’s
partial correlation coefficients were significant
between each cognitive test and both baseline EDSS
(PASAT -0.298; SDMT -0.358; CVLT-II -0.190; COWAT
-0.248; D-KEFS -0.184), and baseline MRI T2 burden
of disease (BoD) (PASAT -0.317; SDMT -0.440; CVLT-II
-0.309; COWAT -0.290; D-KEFS -0.415). A stepwise
regression with the CPI as the independent
variable identified the following predictors:
premorbid IQ (p<0.0001), baseline EDSS (p=0.0001),
baseline MRI T2 BoD (p<0.0001), EDSS change from
baseline over first two years of trial (p=0.0526),
and MRI T2 activity at trial Year 2 (p=0.0098).
“These study results give clinicians a better idea
of the scope and severity of cognitive dysfunction
in MS,” said Dr. Traboulsee. “From an MRI
perspective, it further supports those that
believe lesion burden is a valuable biomarker for
us in monitoring MS patients,” he added.
According to David Bates, MD, a senior UK
neurologist, based at Newcastle Royal Infirmary,
Newcastle, who was not connected with the study,
the research by Dr.Traboulsee and colleagues is
significant, “because it demonstrates, for the
first time, that what we have believed to be true
about the importance of early disease activity and
disability determining long-term outcome is
valid.” “It therefore reinforces our belief in
the importance of early treatment with effective
immunomodulating therapy in multiple sclerosis,”
he told Medscape Neurology. “The fact that
disability or impairment, as measured by the
Kurtzke EDSS, and the MRI T2 weighted ‘burden of
disease’ early in the course of MS predict
cognition and memory 16 years later, implies that
early treatment is essential”.
23rd Congress of the European Committee
for the Treatment and Research in Multiple
Sclerosis: Parallel Session 9 (116). Presented
October 14, 2007.
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