Eculizumab and Pregnancy

Pregnancy is a well-recognised trigger of primary complement mediated aHUS. It is a trigger in ~20% of females who develop aHUS. The onset of aHUS is usually in the final trimester or in the post-partum period. Over half of first presentations of aHUS that occur during pregnancy or post-partum associate with a first pregnancy, with most of the other presentations during a second pregnancy. Genetic abnormalities in the complement system have been identified in over 50% of cases. In the Pre-Eculizumab era half of patients had progressed to end-stage renal failure by 7 years.

Studies of eculizumab in aHUS and pregnancy are very limited. The use of eculizumab should be discussed with the National aHUS service and recommendations will be made on a case by case basis.

This includes:

patients with known aHUS and currently receiving eculizumab who may need monitoring of complement activity during pregnancy and higher doses of eculizumab (see below).
patients with known aHUS / risk of aHUS who are not receiving eculizumab who may develop an episode of aHUS during or after pregnancy

NB patients receiving ravulizumab should consider switching back to eculizumab if planning a pregnancy of if they are pregnant.

Monitoring Eculizumab Therapy during pregnancy

From the limited experience of Eculizumab treatment during pregnancy for complement mediated aHUS it appears that there is an increasing requirement for Eculizumab as the pregnancy progresses.

We recommend ensuring adequate blockade using CH50/AP100 as follows: see forms

At booking/when notified of pregnancy
From ~17 weeks – every fortnight* until 6 weeks post-partum
* If the patient is found to be insufficiently blocked an increase in subsequent doses may be advised and increased monitoring
If by 6 weeks post-partum the patient has not yet returned to the standard eculizumab dosing schedule of 1200mg fortnightly, continue with trough blockade bloods until this regime is achieved.
On each occasion, we would recommend that FBC, U&E and LDH is measured to look for evidence of an episode of aHUS (these should be measured and reviewed locally)

Please note this is a baseline guide only – clinical presentation and blockade results may alter this protocol, with the potential for a significant increase in dosing and monitoring especially towards the end of the pregnancy.

Discussion between the local renal team and the NRCTC consultant will guide this.

Eculizumab dosage alteration should be undertaken in collaboration with the National aHUS centre

Risks of Eculizumab during pregnancy

There is no evidence that eculizumab use has caused harm to the new-born, though most of the data is observational, from eculizumab use in patients with paroxysmal nocturnal haemoglobinuria (PNH). The largest reported experience of eculizumab use during and after pregnancy was in 75 pregnancies in 61 women. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. In another study in which eculizumab was detected in cord blood, there was normal complement activity in 2 new-borns suggesting that even if eculizumab crosses the placenta, the level is not high enough to affect complement activation.

In the PNH study, a total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. These findings suggested that the drug is not excreted into breast milk in measurable amounts and that breast-feeding by patients receiving eculizumab is likely to be safe.