Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis
Achiron A, Kishner I, Dolev M, Stern Y, Dulitzky M, Schiff E and Achiron R;
Commented by , 22 Oct 2004
Background
Relapse rate is reduced in multiple sclerosis (MS) during the last trimester of pregnancy, but disease activity increase in the first trimester postpartum. Treatment safety of intravenous immunoglobulin (IVIG) is well established during pregnancy or postpartum, which is not the case for other immunomodulatory treatments, and IVIG has been shown to reduce relapse rate and disability progression in MS.
Aim
To evaluate relapse rate and effect of IVIG treatment during pregnancy and the post partum period.
Methods
The study was retrospective and evaluated data from 108 pregnant relapsing remitting MS patients. Immunomodulatory treatment was discontinued at least three months prior to gestation. A relapse was defined as objective neurological changes of at least 1.0 point in the Extended Disability Status Scale (EDSS) score.
The study had three groups:
- Group 1 did not receive treatment.
- Group 2 received IVIG 0.4 g/kg body weight/day for 5 days postpartum as well as 0.4 g/kg body weight/day once at 6 and 12 weeks post partum.
- Group 3 received IVIG within 6-8 weeks of gestation, using the same dose regimen, with a booster for 5 days followed by infusions every 6 weeks until 6 weeks postpartum.
Results
Relapse rate per woman per year for the three groups were as follows:
|
Gr. 1 |
Gr. 2 |
Gr. 3 |
| Pre-pregnancy year |
0.79 |
0.90 |
1.20 |
| First trimester |
0.72 |
0.78 |
0.43 |
| Second trimester |
0.61 |
0.58 |
0.15 |
| Third trimester |
0.41 |
0.39 |
0.0 |
| Postpartum |
1.33 |
0.58 |
0.28 |
Pre-pregnancy relapse rate was higher in group 3. There were no significant differences between other baseline characteristics.
During the pregnancy period there was a significant reduction of relapse rate in group 3.
In the postpartum period the relapse rate was significantly reduced in groups 2 and 3.
Additional statistical analysis correcting for changes in pre pregnancy relapse rate still suggested beneficial effect of IVIG in group 2 and more pronounced in group 3.
No serious adverse events were recorded.
Discussion
The authors demonstrate a reduction of relapse rate during pregnancy in MS patients who received IVIG treatment. The patients who received treatment for the whole pregnancy and postpartum period had the best therapeutic effect.
The results of the study are interesting but should be interpreted with caution for several reasons. First of all the study was retrospective, open and not placebo-controlled and the results therefore only guiding. Furthermore, the baseline data were not comparable, since pre-pregnancy relapse rate was higher in the group who received treatment for the whole gestational period. In this way there could be a selection bias between the two treatment regimens, and the statistical effect of regression towards the mean could also differ.
Finally, the authors only used a single dose IVIG although the ideal dosage in MS treatment is not known.
The study does not live up to standards regarding treatment evidence and was not designed to answer some of the compelling and basic questions regarding treatment of MS patients with IVIG. Still the results have interest, although further studies are needed in this field.