Tuesday, 2 September 2014

ClinicSpeak: pregnancy outcomes with natalizumab exposure

Is pregnancy the great DMT differentiator? #ClinicSpeak #MSBlog #MSResearch

"I predict that pregnancy will be the next marketing battleground for the DMTs. Which is the safest drug to take during pregnancy? The answer is none. None of the current DMTs have a license to be used during pregnancy. The following study, albeit small, looks at pregnancy outcome in babies with first-trimester exposure to natalizumab and concludes that foetal exposure to natalizumab in early pregnancy does not appear to increase the risk of adverse pregnancy outcomes. This study is only powered to detect common adverse outcomes and won't detect rare events. It is however important as it is provides some reassurance to women with highly active MS that they can fall pregnant on natalizumab before stopping it. This is important as it hopefully will prevent rebound disease activity as pregnancy in itself is disease-modifying. The other option open to women with highly-active MS is to opt for alemtuzumab treatment and to try and fall pregnant about 4 months after the second course of treatment. This is hopefully in the window before the peak incidence of thyroid autoimmunity develops, but after treatment when MS is hopefully under control. Thyroid autoantibodies, and presumably other autoantibodies, that can develop post-alemtuzumab could cross the placenta and cause disease in the unborn child."

"Other treatment options available include glatiramer acetate (GA) that appears to have a very good safety profile in pregnancy and a large number of neurologists are prescribing GA as their drug of choice in women wanting to have children. Dimethyl fumarate (DMF), as a normal metabolite, has the potential to be used in pregnancy. But until the there is more real-life pregnancy safety data I would be reluctant to prescribe in pregnancy based on this lone. What about emerging therapies? Ocrelizumab, a potent B-cell depleting antibody, may work as an induction agent, but there are reports of B cell depletion in babies born to patients treated with rituximab. Clearly, these anti-CD20 antibodies hang around longer in the body than alemtuzumab." 

"What would I do? If had highly active MS and was on natalizumab and was at high-risk of rebound on withdrawal of natalizumab I would probably follow the strategy below. If was deciding on which treatment to start and was planning to have children in the future, I would consider alemtuzumab. Clearly, pregnancy will not be the only factor differentiating the available therapies, but an important one nevertheless."

"What is clear is that we need more data!"



BACKGROUND: Safety data on first-trimester natalizumab exposure are scarce, as natalizumab is usually withdrawn three months before pregnancy.

OBJECTIVE: The objective of this paper is to investigate the foetal safety of exposure to natalizumab during the first trimester of pregnancy using disease-matched (DM) and healthy control (HC) comparison groups.

METHODS: total of 101 German women with RRMS exposed to natalizumab during the first trimester of pregnancy were identified. Birth outcomes in the exposed group were compared to a DM group (N = 78) with or without exposure to other disease-modifying drugs, and an HC group (N = 97).

RESULTS: A total of 77, 69 and 92 live births occurred in the Exposed, DM and HC groups, respectively. The rates of major malformations (p = 0.67), low birth weight (<2500 grams) (p = 1.0) and premature birth (p = 0.37) did not differ among groups. Higher miscarriage rates (p = 0.002) and lower birth weights (p = 0.001) occurred among the Exposed and DM groups, as compared to the HC; however, there was no significant difference between the Exposed and DM groups.

CONCLUSION: Exposure to natalizumab in early pregnancy does not appear to increase the risk of adverse pregnancy outcomes in comparison to a DM group not exposed to natalizumab.

"The following is a table comparing the attributes of natalizumab and alemtuzumab treatment in MS; pregnancy is an important differentiator." 



CoI: multiple