Patient Selection and Safety With TNF Inhibitors - Episode 25
Christopher Robinson, MD, MSCR, FACOG: One common concern when trying to achieve pregnancy is, “If I don’t get a first pregnancy test within a month or 2, what is going on? What are the possibilities? What things can I potentially modify?” Another is, if there is a miscarriage, “Was the miscarriage caused by my disease, or was it a natural state?”
Disease control is important in reducing inflammation, which also improves pregnancy outcomes. But I think it’s also important to recognize that up to one-third of miscarriages are natural miscarriages. In other words, those that would have happened in women who have no disease whatsoever. The key is not to become discouraged when a miscarriage does occur but to control the factors that you can. That’s usually the way I discuss it with patients. We try to maximize disease control in order to improve the likelihood of conception.
There are other things women can focus on, such as timed intercourse around the time of ovulation. We know that women, when they get past 30 years of age, may have a decrease in the natural fertility that they may have had prior to 30 years of age. If a person doesn’t conceive after 6 months of regular intercourse, attempted timed intercourse for pregnancy, they might even consider reaching out to a reproductive endocrinologist who can assist with an evaluation to see if there are other factors that should potentially be considered in achieving pregnancy.
When planning a pregnancy, certainly 1 of the focuses of the mother is, “I want to have the healthiest pregnancy possible.” In counseling, we focus on things like avoiding alcohol and avoiding smoking. The mother begins to focus on whether there are any things that she is taking or exposing her baby to, potentially inside, that she can minimize during pregnancy. The important portion of this that we like to point out to patients is that we want to have a healthy mother and achieve a healthy pregnancy. Both are very, very important. And when we look at autoimmune disease, keeping that mother under control—keeping her autoimmune disease in remission—is very important in achieving that optimal pregnancy outcome.
When we look at that, we look at medications that can be used. Believe it or not, what a lot of people don’t realize is that the majority of medications used to treat autoimmune disease—especially relative to bowel disease and that sort of thing—can be used safely in pregnancy. Many women are currently being managed, for instance, on biologic therapy. Biologic therapy is aimed at different aspects of suppression of the immune system—many of those being TNF [tumor necrosis factor]—alpha inhibitors that they may be using, adalimumab or infliximab being the most common and most studied across pregnancy and being very effective at suppressing and keeping autoimmune disease in remission. Certolizumab is also an option in the anti–TNF-alpha group, which has a very specific property. It doesn’t cross the placenta effectively. It does not have the ability to cross the placenta even to the baby.
We have these discussions with women in a group-based setting. You ideally need a group of physicians who you are working with. You come to the table, usually with a GI [gastrointestinal] specialist who has been managing your condition. You then meet with a maternal-fetal medicine specialist like me, and we begin to really focus on what has been the course of your disease over time. How has it affected your life? Have you had surgeries in the past? Has there been the possibility of needing a diversion surgery like a J-pouch, or an ileal conduit? Have they had other complications that may be present?
And then we focus on medication therapy that has worked and has not worked for them, with a focus on reducing steroids. I think that’s really important, and that’s where the anti—TNF-alpha agents have really helped us. We can often reduce those steroids to none. And so we can remove steroids from the table and keep them on those medications throughout pregnancy and even beyond that. You have to think about the course of care even into breastfeeding, postpartum, and ongoing care.
When we’re thinking about a woman of reproductive age, 1 of the key features is thinking that women in America, on average, will have slightly more than 2 children—between 2 and 3 children. In knowing that, and also in knowing that pregnancy is not always planned, it is a good idea to begin thinking about that process. Even from the GI perspective, the gastroenterologist is evaluating that patient who is of reproductive age in making decisions about medication use that would be safe.
There are some medications that we don’t recommend. For instance, methotrexate is a good example. This is used in autoimmune disease, especially for the treatment of Crohn disease and ulcerative colitis. With that medication, for instance, we recommend that a woman be off treatment for at least 3 to 6 months before she becomes pregnant. Tofacitinib is a medication that’s recommended to be avoided in a first trimester. If a woman were to be started on either of those 2, I think it’s important that she also know to talk to her physician as soon as she recognizes she’s pregnant, so they can make appropriate plans for transitioning, if that is the best medication for control of her disease.