Male fertility on natalizumab

In response to the comment re male fertility on natalizumab.

Wehner et al. Effects of natalizumab, an alpha4 integrin inhibitor, on fertility in male and female guinea pigs. Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):108-16.

Background: Natalizumab is a humanized monoclonal immunoglobulin IgG4 antibody directed against the human adhesion molecule subunit, alpha4 integrin, disrupting interaction with its binding partners. As alpha4 integrins and/or their binding partners appear to be involved in reproductive function, the effects of natalizumab on fertility in male and female guinea pigs were investigated.

Methods: Natalizumab was administered by intravenous injection every other day at doses of 0, 3, 10, and 30 mg/kg. Males began treatment at least 28 days prior to mating until they were sacrificed for the study (approximately 3 to 5 days after mating). Dosing in females was done from gestational day (GD) of an existing pregnancy to GD 30 of a second pregnancy.

Results: In male guinea pigs, natalizumab treatment had no effect on sperm parameters, reproductive organ weights, organ-weight ratios, or histology of the testis or epididymis. Natalizumab did not affect the ability of treated males to produce pregnancies in untreated females. In female guinea pigs, no treatment-related changes were seen in uterine weights or ovary weights. Pregnancy rates were, however, reduced in females treated with 30 mg/kg natalizumab, but not those treated with 3 or 10 mg/kg. Pregnancy rates were 63, 67, 67, and 30% for groups treated with 0, 3, 10, and 30 mg/kg, respectively. The effects observed at 30 mg/kg were at exposures 36-fold those observed in humans.

Conclusions: Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with very high doses of natalizumab.

"Biogen-Idec and Elan, the companies that produce and market natalizumab, are obliged to recommend that nobody should fall pregnant whilst on natalizumab (woman on natalizumab or the female partners of men). The recommended wash-out period is at least 3 months."

"Based on the above animal studies and that fact that Natalizumab is an antibody that is unlikely to get into the testes, I recommend to men on natalizumab that they can go ahead and have a family without having to stop the drug."

"Natalizumab is considered to be in pregnancy category C meaning that it caused some harm to foetuses in animal studies but the effect in humans is unknown."

Conflicts: multiple

Other posts of interest

31 May 2011
Of the women exposed to natalizumab during pregnancy, 29 women gave birth to 28 healthy children; one child was born with hexadactyly (an extra finger), 5 pregnancies ended in an early miscarriage and one woman ...