Does alemtuzumab treatment increase your chances of having a miscarriage or premature birth?

A large systematic review of numerous studies involving women with ‘normal thyroid function’ showed a strong association between the presence of anti-thyroid peroxidase antibodies and having a miscarriage and/or premature birth, i.e. the chances were increased by approximately 3.9x and 2.1x, respectively.

As alemtuzumab treatment increases the chances of women with MS getting autoimmune thyroid disease it is likely to increase a woman’s chances of having a miscarriage and/or preterm birth as well. I think this issue needs to be defined for alemtuzumabers ASAP. Why? One of the main reasons why women with MS choose alemtuzumab as a treatment is to start or extend their families. Knowing that secondary autoimmunity may decrease their chances of a successful and favourable pregnancy outcome may affect clinical decision making.

It has been suggested that by giving women who have anti-thyroid peroxidase antibodies the thyroid hormone,  thyroxine, you may be able to suppress the thyroid gland and hence reduce the risk of adverse pregnancy outcomes. Unfortunately, this is not the case. In the large study below use of levothyroxine in women with normal thyroid function and anti-thyroid peroxidase antibodies did not result in a higher rate of live births compared to placebo

Dhillon-Smith et al. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. N Engl J Med. 2019 Apr 4;380(14):1316-1325.

BACKGROUND: Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.

METHODS: We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.

RESULTS: The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14).

CONCLUSIONS: The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

CoI: multiple

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  • It seems to me that alemtuzumab is prooving more risky than natalizumab now, with opportunistic infecitons and all the rest.

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