Advances in the Management of Plaque Psoriasis - Episode 7
Mark Lebwohl, MD: Prior to the current era of biologic therapy, many of the treatments that we used for psoriasis were not ideal for women of childbearing potential. Methotrexate was used to induce abortions and certainly is associated with birth defects. Acitretin is associated with awful birth defects. The third oral medication we used to have, cyclosporine, was pregnancy category C back in the day when the FDA had pregnancy categories but mostly because it was used in sick transplant patients. When it was used for psoriasis, it was actually probably safer than in the other populations. But the bottom line is that that drug used to be the one we went to for patients with severe psoriasis flares during pregnancy because it had a track record in transplant patients. The main adverse effect was actually, if I remember correctly, a reduction in birth weight, on average. It was a small reduction. So it was a fairly safe drug to use.
Along come the biologics and these now, by and large, are pregnancy category B when we had pregnancy categories. They were safer to use, according to the FDA package insert, but also they were safe to use in general. Because the frequency of birth defects and miscarriages is so high—roughly 1 out of 6 pregnancies in the United States ends in a miscarriage and approximately 1% to 2% of pregnancies end up with a major birth defect even in untreated patients—many pregnant women don’t want to take a chance, and stop all therapies prior to pregnancy.
Certainly, we know that antibodies cross the placenta, so all of the medications that we had prior to certolizumab did actually get to the fetus. They crossed the placenta and had an impact on the developing fetus. None of them are associated with specific birth defects. Even though they cross the placenta, we’re not aware of a birth defect that they cause. Certolizumab was the first 1, and it’s a pegylated TNF [tumor necrosis factor] blocker, so it doesn’t cross the placenta, and therefore presumably might be safer during pregnancy. I will say that I do prescribe certolizumab in women of childbearing potential for that reason.
We have a lot less data on the newer biologics, but it appears that they are antibodies, so certainly some of them may cross the placenta. Some of them appear not to cross the placenta for reasons that are unclear. You would expect that they might have an impact on the fetus, but again, none have been associated with a specific birth defect. I suspect that if the FDA were still using pregnancy categories, all of the new antibodies would be listed as pregnancy category B. Although, in a monkey model that is often used for testing in pregnancy, with some of the drugs as they give, for example 20 times the maximum dose that we would give to humans, you see some fetal death. We don’t have enough information to say that they are safe.
One of the advantages of some of the newer drugs is that they can be stopped prior to pregnancy, and it takes a while for psoriasis to reoccur. Because it takes a while for psoriasis to reoccur, you can actually plan a pregnancy and plan to administer the drug prior to conception. Then you can have the patient hold off on re-treatment until after the pregnancy. Some of my patients have chosen to do that.
In pediatric patients with psoriasis, we have a little bit more of a challenge because many of the drugs that we use are not approved for pediatrics. Actually, some of the older drugs are not specifically approved for pediatrics. But because they’re cheap, insurers allow us to use drugs like methotrexate and cyclosporine. Drugs like etanercept are approved even in children, and that is easier to get for that reason. In some parts of the world, adalimumab is approved in children. Ustekinumab is approved in teenagers and hopefully will be approved in pediatrics as well. If I had the opportunity to pick the drug I’d like to use, I would use 1 of the drugs that’s given infrequently like ustekinumab, which can be given as infrequently as every 3 months. Some of the IL-23 [interleukin-23] blockers are also ideal in that setting.
But children more than adults, especially teenagers and even children younger than teenagers, are bullied and picked on because of their psoriasis. Other kids often think that their psoriasis is contagious. They don’t have the knowledge base about psoriasis that makes them sympathetic to children who have the disease. I think it’s even more important to treat psoriasis in children than in others. Children will readily put up with any treatment that clears them, and that includes etanercept, which is given weekly. Even frequent treatments are acceptable to kids. Remember that children with diabetes take insulin, and they don’t have a choice. They have to take insulin injections. So we can train our patients to get injected. But again, if I had my choice, I’d give 1 of the less frequently injected drugs.
Transcript edited for clarity.