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Intravenous immunoglobulin in primary and secondary
chronic progressive multiple sclerosis: a randomized placebo controlled
multicentre study.
Mult Scler. 2007 Jul 10
Pohlau D, Przuntek H, Sailer M, Bethke F, Koehler J, Konig N, Heesen C, Spath P, Andresen I.
Department of Neurology, Multiple Sclerosis Center, Kamillus-Klinik Asbach.
In
patients with relapsing-remitting multiple sclerosis (MS), IVIG was
shown to reduce the relapse rate and progression of disability. In
patients with chronic progressive MS, a beneficial effect of IVIG was
not documented in placebo controlled studies. This trial investigated
the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic
progressive MS.
Two-hundred and thirty-one patients stratified for PPMS
(n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per
month or to placebo for 24 months. Primary endpoints were 1) the time
to sustained progression of disease identified as worsening of the
expanded disability status scale (EDSS) sustained for 3 months, and 2)
the improvement of neurological functions defined by a patient's best
EDSS score. Secondary endpoints were the proportion of patients with
sustained progression, the relapse rate, the assessment of fine motor
skills, visual evoked potentials, contrast sensitivity, depression and
quality of life. Analysis of the intention-to-treat (ITT) population of
combined PPMS and SPMS patients showed that the mean time to sustained
progression was 74 weeks in the IVIG compared with 62 weeks in the
placebo group (P=0.0406). When PPMS and SPMS patients were analysed
separately, the time to sustained progression was also longer in the
IVIG group, but the difference was not significant. There was no
IVIG-mediated improvement in neurological functions. In the combined
per protocol (PP) treated patients, IVIG treatment prolonged time to
sustained progression by 13 weeks (P=0.0396). PPMS patients, but not
SPMS patients showed a slight favourable IVIG effect on the best EDSS
score. In the combined ITT population there were less patients with
sustained progression in the IVIG than in the placebo group (P=0.028).
The difference was significant in PPMS (P=0.016), but not in SPMS
patients. In the combined PP population, there was a trend for a
favorable IVIG effect on the rates of patients with sustained
progression. In patients with PPMS, this IVIG effect reached
significance (P=0.036). Other secondary endpoints did not show
significant differences between treatment groups. Eighteen patients
with PPMS and 102 patients with SPMS withdrew from the study for
various reasons. Treatment was generally well tolerated. It was
concluded that monthly IVIG infusion could delay progression of disease
in patients with PPMS, and that there was a trend in favour of IVIG
treatment in patients with SPMS.
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