March 2023 Update on using Benlysta during pregnancy
A March 2023 study found low B-cells at birth in the newborn baby of a woman who received Benlysta into the 3rd trimester… discussed below at this link.
A research study from the Netherlands showed fascinating results regarding using belimumab or Benlysta during pregnancy. This is very important because we need more safe drugs to use for lupus patients during pregnancy.
Some Background on Using Benlysta During Pregnancy
- I suspected that Benlysta (belimumab) may be found to be effective and safe during pregnancy for the reasons below.
- Benlysta is a very large molecule and like other biologics would probably not pass through the placenta well during the 1st and 2nd trimesters. Starting in the 2nd trimester, some may enter the fetus, and somewhat more would enter during the 3rd trimester.
- The TNF inhibitors (like certolizumab or Cimzia) have been shown to be safe during pregnancy. In fact, certolizumab may reduce fetal loss in SLE women who are positive for antiphospholipid antibodies.
- I have suspected that stopping Benlysta when a woman becomes pregnant would increase the risk for a lupus flare, which is one of the worse things that can happen during pregnancy, and that continuing Benlysta to keep lupus under control is probably a better thing to do.
- GSK (the maker of Benlysta) has kept a Benlysta Pregnancy Registry for over a decade. Petri, et al showed that 68% of Benlysta patients had successful pregnancy live births, which is comparable to what is expected historically in SLE patients (48% to 75%) and was better than a comparison “placebo” group. However, since the study is not a double-blind placebo-controlled trial, it is difficult to make firm conclusions from the registry. However, the results were reassuring.
- Animal studies in monkeys showed no Benlysta problems in pregnancy. The study even used much higher doses of Benlysta than we use in humans.
2023 Research Shows that Benlysta During Pregnancy was Safe
Ghalandari et al from the Netherlands reported their results of using Benlysta during pregnancy in the March edition of the journal Lupus.
They looked at a total of 87 pregnant women with systemic lupus erythematosus who were on Benlysta. 67 of them stopped Benlysta when they found they were pregnant; 20 patients continued Benlysta.
The statistics showed:
When Benlysta was continued during pregnancy, there were numerically a similar number of live births and no evidence for birth defects nor side effects to the mothers or babies.
There was no increase in birth defects in the Benlsta group. SLE patient births have approximately 13.6% congenital malformations and the Benlysta group had 9.5% (lower than expected). This was a small study. However, the much larger Benlysta Pregnancy Registry also did not show any unexpected signals for birth defects. This is very reassuring.
The authors point out that there were a high number of fetal deaths in both groups. Historically, we can expect 25% to 52% fetal losses in SLE patients. Yet, this is probably a group of patients biased towards an increased risk for complicated pregnancies in that Benlysta is used for patients with more severe disease. In addition, the Benlysta group has a potential bias for increased complications due to a high number of spontaneous reports (see below).
A very important thing to point out is that none of the Benlysta patients flared, while 4 patients flared who stopped their Benlysta. Flaring during pregnancy is very bad. When SLE flares in the 1st or 2nd trimester, that mother is three times more likely to lose her baby compared to not flaring.
More Notes from the Authors
Only one baby had very low numbers of B-cells (a type of white blood cell), called B-cell depletion, but this occurred in a woman treated with rituximab during pregnancy (this is a known side effect of rituximab.
The authors also point out that there were more spontaneously reported patients in the Benlysta continuation group (3 out of 5 patients) compared to the discontinuation group (fairly equal numbers). The doctors reported the results on the other patients specifically for the study. The significance of this is that doctors are much more likely to spontaneously report a patient if that patient had an adverse outcome. This could potentially skew the Benlysta group toward having more bad outcomes. But we did not see that.
A major negative of this study is that it was overall a small study. However, when combining these results with the much larger Benlysta Pregnancy Registry, this is reassuring regarding the safety of Benlysta during pregnancy.
It is also good to know what our peers are doing. There seems to be a large number of rheumatologists in The Netherlands who felt the benefits of Benlysta outweighed the potential for side effects (look at my reasons at the top of this blog post), that they used Benlysta during pregnancy.
When should Benlsyta be used during pregnancy?
Bitter H et al, from Norway, reported their results of measuring belimumab drug levels and B-cell levels in a pregnant woman with SLE who received belimumab until the 26th week (early 3rd trimester). By the way, this is longer than I would have used Benlysta as we know that biologics start to enter the placenta and fetus in small amounts beginning in the 2nd trimester and gradually increases even more in the 3rd trimester, increasing the risk for possible immunosuppression in the newborn baby.
They showed that the newborn baby had lower than normal B-cells at birth, which then normalized at the 4-month blood draw. They did not report 1, 2, or 3 month results. The baby responded well to vaccines and had no side effects to belimumab (Benlysta) and was followed up to the 6th year.
How this will change my practice
I would add Benlysta to the list of SLE pregnancy-safe drugs along with hydroxychloroquine (a necessity!), azathioprine, tacrolimus, and steroids.
Just as we learned over time that the biologic TNF inhibitors were safe to take during pregnancy, we are now learning the same about Benlysta.
I am more apt to continue Benlysta during pregnancy rather than stop it. Preventing flares during pregnancy is very important and our choices for safe lupus drugs during pregnancy are very limited.
In addition, it appears that Benlysta is safe to take (one of the most important things). There certainly seems to be enough evidence that it does not cause birth defects.
I would stop Benlysta before the end of the 2nd trimester if the patient is doing well. Some Benlysta could get into the baby during the 3rd trimester as illustrated in the case above.
This is one unanswered question so far. When in the 2nd trimester would be best to stop Benlysta and prevent significant amounts from entering the fetus?
If doctors use a biologic, like Benlysta, during the 3rd trimester (such as in a woman at high risk for flare), they would need to avoid giving some of the recommended vaccines to the baby (the ones with live virus) during the first few months. I would also follow CD19 levels in the baby and wait until normalized before giving vaccinations.
However, I always make such a decision after a careful discussion with the mother, weighing the risks vs benefits. Using a team approach and mutual decision-making is important for all aspects of high-quality lupus care.
This is another major milestone in taking better care of lupus patients!
Donald Thomas, MD, author of The Lupus Encyclopedia
Disclosures: Dr. Thomas is on the Speaker’s Bureaus of GSK, AstraZeneca, Aurinia, and Exagen
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