Following on from its recent article about the safety of eculizumab ( see here ) the alliance has looked at two topics that matter to aHUS Patients. Pregnancy and Allergy.
One statistic from the safety report article that resonated was how few of the aHUS pregnancies resulted in live births. Much fewer than PNH pregnancies where mothers were using the same drug. Why might that be so ?
There is nothing in the Safety Report to explain whether this was an adverse affect of eculizumab. If it was there would be an expectation that data would be similar for PNH and aHUS. So maybe the relative seriousness of the disease during pregnancy might explain it but aHUS mothers suffered relatively fewer miscarriages and still births.
The statistic which differed markedly was how many parents elected to terminate the pregnancy. More aHUS parents chose to do that than PNH parents in the period 2007 to 2016 . One in five aHUS pregnancies were terminated.
The alliance wrote to the authors of the article to see if they could explain the reason for it but they have not been able to explain the difference.
Pregnancy is a trigger of aHUS but most commonly after giving birth. It is not a trigger of PNH but clotting during pregnancy is a very serious complication for PNH mothers none the less.
It is not clear from the Safety Report whether the aHUS mothers were diagnosed with aHUS before or during pregnancy or whether eculizumab was prescribed as a precautionary or rescue treatment. So it difficult to understand in what circumstance the decisions were made and on what evidence were they based.
The default advice to aHUS women 10 or more years ago would be avoid pregnancy or to terminate. Those onsetting during early pregnancy may be similarly advised.
One possible reason for such advice would be the lack of publicly available data in the early days of the safety of eculizumab to the foetus. Patients who were pregnant or planning to be pregnant were excluded from eculizumab trials.
Now that more is known, has advice changed to help make such decisions and will there now be fewer self determined terminations of aHUS babies.
Evidence for family planning decisions is on the aHUS Research Agenda.
A second topic which features in the aHUS community’s discussions is being allergic to eculizumab. This side effect did not feature at all as a serious side effect of eculizumab in PNH nor aHUS treatment.
Yet almost coincidental to the Safety Report Article publication was another about successfully desensitising a child to its allergic reaction to eculizumab. Basically a protocol was found, as used elsewhere, to give smaller infusions more regularly but with intervals. Sensitivity was eliminated.
The alliance now understands that allergic events were reported and recorded in the adverse events database and Registry and Alexion were aware of the above case study. The cases of eculizumab sensitivity were reported infrequently and as not serious clinically, which is why it did not feature along with the more serious adverse events in the Safety Report.
Adverse event reports are still collected by Alexion as it is obligated to do whilst the drug is marketed. The Global aHUS Registry is also collecting data on those aHUS patients it is still following and will continue to follow for another five years so adding to the pre 2016 reports.