A two-year study of azathioprine combined
with interferon beta-1b (IFNB-1b) was carried
out in 10 SPMS patients who had not responded
well to IFNB-1b alone. The findings showed
that:
combination therapy was safe and
generally well tolerated;
annual relapse
rate was reduced and there was
a significant trend for EDSS improvement;
there
was a significant improvement in neuropsychological
tests after 2 years;
total lesion
load
measured by MRI decreased at
12 and 24 months.
Details
Combination therapy may benefit the subgroup
of patients with secondary progressive
multiple sclerosis (SPMS) who do not
respond to interferon
beta (IFNB). Researchers from Spain performed
a two-year study of azathioprine (AZA)
which is an oral immunosuppressive medication,
combined with IFNB-1b in SPMS patients
who had not responded
well to IFNB-1b alone. Patients with
SPMS were eligible for this non-controlled
prospective
study if they had two or more relapses
requiring corticosteroid treatment or
deteriorated by
at least 0.5 points on the Expanded Disability
Status Scale (EDSS) while on IFNB-1b
in the
year preceding the study. Patients were
to continue treatment with IFNB-1b (8
MIU daily,
subcutaneous) and received AZA (50 mg
three times a day, oral). Safety was assessed
in terms of adverse reactions and laboratory
measures graded according to the World
Health Organization
toxicity scale. Efficacy was explored
by
changes in relapse rate, EDSS, 9-hole
peg
test (9-HPT),
neuropsychological scores, and magnetic
resonance imaging (MRI) results. Neutralizing
antibodies
(NAB) were measured. Ten SPMS patients
(6 females) with a median EDSS score
of 4.5
were enrolled.
One patient withdrew because of gastrointestinal
complaints, one was withdrawn owing to
poor compliance, and 8 patients completed
therapy.
The only frequent side effect was lymphopenia,
reported at least once in all patients.
Annual relapse rate was reduced by approximately
50 % in the second year. There was
a significant
trend for EDSS increase. Total lesion
load measured by MRI decreased at 12 and 24
months; only one patient had active lesions.
No changes
were seen in the 9-HPT. There was a significant
improvement in neuropsychological tests
after 24 months (p = 0.045). One patient
tested
positive
for NAB throughout the study, and transient
NAB were detected in 4 patients. In conclusion,
combination therapy with IFNB-1b and
AZA
was safe and generally well tolerated
in patients
with SPMS. Strict clinical and laboratory
monitoring is recommended during this
combination therapy.
It is important to note that while this
may suggest additional options for advancing
SPMS, larger controlled trials would
be
necessary
to confirm these results.
ASK Information System Code: 1.4.1.60.1.t
Disponible en français.
Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or
therapy, but provides information to assist individuals in making their own
decisions.
