Transcript: Lisa Sammaritano, MD, on the New ACR Guideline for Managing Reproductive Health

Rebecca Mashaw: Hello, and welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I'm your moderator, Rebecca Mashaw with Consultant 360 Specialty Network. With us today is Dr Lisa Sammaritano, associate attending physician from the Hospital for Special Surgery and associate professor of Clinical Medicine at Weill Cornell Medical College in New York. As a member of the group that developed the American College of Rheumatology's recently released guideline for the management of reproductive health and rheumatic and musculoskeletal diseases, Dr Sammaritano will give us some special insight into the challenges of helping women with rheumatic diseases to achieve healthy pregnancies. Thank you for taking the time to speak with us. Before we get into the nitty-gritty of the guideline, let's talk about the overall recommendations. There were 131 of them. Of course, we can't get to all of them today, but can you talk about the most important recommendations for managing rheumatic disease in pregnant women? Lisa Sammaritano: Sure. I think that many of the recommendations are quite specific, but overall the point of the guideline was actually to address all rheumatic disease patients and, in addition to pregnancy, to cover other reproductive health issues. I would say the overall methods that we tried to communicate is that it's very important for a rheumatologist to discuss reproductive health issues and planning with their patients and to communicate as well with the patient's OB/GYN. There are a lot of very specific recommendations, as I said, but the main points are this: that if someone is not in a situation medically where they should be getting pregnant, that they should use effective contraception. When they do get pregnant, it's best to plan ahead of time, because pregnancy outcomes are the best—both in terms of the mother's health and the outcome of the pregnancy itself—in women whose disease is well controlled on pregnancy compatible medications. That takes a little bit of planning oftentimes. Discussing this ahead of time, making changes in medications or therapy ahead of time, can all lead to optimal pregnancy outcomes. Rebecca Mashaw: What about those tough-to-treat patients with rheumatic diseases who are pregnant? What would their treatment regimens look like? Lisa Sammaritano: That's a tough question. They are tough-to-manage patients, and it depends of course on the details of the patient's diagnosis and their particular manifestations of the disease. In general, we hope that these are the patients—of all of our patients—who do plan ahead of time with us, because the hardest part of managing these patients may be in the months or even a couple of years prior to a pregnancy. We will try to control disease well with medicines that are safe to take during pregnancy. We need to change the medicine and then make sure that the medicine is tolerated, and that it's effective for that patient. That could all take some time. For example, I had a patient with lupus and kidney inflammation who was well-controlled on medication—mycophenolate. We changed her to a common medicine that is pregnancy compatible—azathioprine. It did not control her disease, we had to go back, retreat her with her previous med and finally then, put her on yet another medicine—tacrolimus—that is just now being used more commonly for rheumatology patients during pregnancy. On that medication, her disease was well-controlled and she really had not one, but two successful pregnancies to date. But it took about two years before we were able to get things in a situation on the right meds for her to go ahead and become pregnant. It really does depend, of course, on the individual patient but very much the planning and then monitoring both before and after. Rebecca Mashaw: Biologics are becoming increasingly important for treating rheumatic diseases. Where do they fall under the recommendations for pregnant woman with rheumatic disease? Lisa Sammaritano: It's really been an explosion in therapy over the past years. I would say that when it comes to pregnancy, at this point in time, not all biologics are equal. That is because we have more data on certain types of biologics than on others, simply because some of these biologics have been used in other types of chronic illness. For example, TNF inhibitors have been used for many years for inflammatory bowel disease, and there's a large literature that documents really the safety of these drugs during pregnancy. Both from information and published reports on rheumatology patients and also on these other types of patients with inflammatory disorders—through the process of the guideline, we solved that based on that data that it was OK for TNF inhibitor medications to be continued certainly through the first and second trimesters and, if warranted, through the third trimester. Biologics, the classical kind of biologic, is based on an IgG antibody, and it's important to know that they pass through the placenta in a different kind of way. It's not like a chemical that diffuses through the placenta. For these types of biologics, they don't pass through the placenta until the end of the first trimester or beginning of the second trimester when they're special receptors that develop. However, in the third trimester, biologics are transferred across the placenta in very high amounts so that when the baby is born, they will have high levels in their blood. As a result, for TNF inhibitors, we generally recommend continuing them up to the time of pregnancy, if needed, through the first and second trimester and, if absolutely needed, then through the third trimester. Knowing though that if continued through the third trimester, the newborns will have levels of this drug on their blood that are quite high and so are at-risk for immunosuppression. As a result, we do not recommend live vaccines in the first 6 months for these babies, although there are reassuring studies showing that in general they are not developing infections at a higher rate. For the regular vaccines that they get, they are mounting an appropriate immune response as they should be. The biologics that are not TNF inhibitors are not as well-studied. There's no reason to think that they would be very different, but we can't base our therapy on theory. We're really waiting for more information from a lot of the registries that have been set up for those patients who do continue medication through pregnancy. I should mention that in terms of TNF inhibitors, there is one that does not have the same heavy chain and is not transferred across the placenta, and that's certolizumab. That is even a little more reassuring for use in that setting. Some of the other new medications that are novel small molecule meds are also not recommended for use in pregnancy at this time. Again, not because we know of any adverse outcomes, only because we don't have enough information yet. One of the goals of our guideline is that it should be updated periodically, and I think that this part of the guideline, specifically looking at biologics and other medication, that's probably going to be the part that changes most frequently as we get more information from more studies then more registries. Rebecca Mashaw: When we spoke to you in December about general reproductive issues among women of child-bearing age, you had mentioned that the use of medication for rheumatic disease has changed and evolved over the past years, which was one of the key reasons why an official guideline was being created. What is the evolution of medication for rheumatic diseases look like and how has that affected this new guideline? Lisa Sammaritano: As we discussed, biologics have been the area where we've had the most new medications and, really, increasingly effective medications. Overall, this evolution in terms of medication has made a huge difference for patients to have disease under control, and not only that, but under control for long periods of time. In years past, there were patients who could never get their disease under control, so that even if things calmed down at a point where they could consider conceiving and having a pregnancy, they might have developed, during that time of active disease for many years, organ dysfunction that was lasting, whether kidney failure or other organs. The improved medications in a broader spectrum in terms of types of medicines, types of targets I think has made our patients as a whole more healthy throughout their course, so that they are more likely to be in a position where they can consider not just pregnancy—which of course is physical stress in it of itself—but also having a family and child-bearing which is another kind of physical and emotional stress. If someone is in chronic pain or is disabled, those decisions are much harder to make. I think overall that the spectrum of medication that has been expanding over the past years have allowed healthier patients, more choices, and a better physical condition in which to think about, plan, pregnancy, and, of course, to raise a family. Rebecca Mashaw: Very good points. This is also the first official guideline that addresses the intersection of rheumatology and obstetrics and gynecology to further reinforce the value of multidisciplinary teams. In your practice, how do you include your peers in the OB/GYN area into your patient-management strategy? Lisa Sammaritano: I feel that for myself, I've been very fortunate in that when I started my practice, I was in the hospital in a rheumatology program that already had an interest in this area. It was relatively easy for me to reach out to OB/GYN and other gynecology specialists, whether general gynecologist or the fertility specialist. We have actually had a long-standing collaboration with them, but recently, we formalized that in a structure that we call the Rheumatology-Reproductive Health Program. We've identified those specialists in different areas of OB/GYN who are interested in our patients and happy to see them, sometimes at a moment's notice. We have a lot of support from them. We also tried to educate each other. I have given a number of talks to the OB/GYN department. We have them come over and talk to us and to our fellows. It is not just about an individual patient—one-on-one—but that everyone gets a chance to hear about how to manage certain problems. We also invite them to our clinical conferences where we might present challenging patients so that we can get their input and maybe hear a variety of opinion. Now, as I've said, I've been very fortunate that I'm in this kind of situation. The whole point of the guideline was to try and take a little bit of this fortunate situation and make it available to other rheumatologists who may be in practice somewhere where they don't have easy access to OB/GYN support. That really was a big message that we try to incorporate into the guideline. We try to educate in terms of providing background information on the latest in terms of contraception, pregnancy management, so that our fellow rheumatologists would be up-to-date in this area. Then provide guidance in terms of how to stratify patients according to risk and how to think about the issues for them. Then finally, strong encouragement to reach out for any individual patient to their OB/GYN for whatever the issue is, whether it's deciding on contraception, whether it's talking about plans for an in-vitro fertilization cycle, or planning for pregnancy and then management during that pregnancy. We're hoping to take a bit of our experience, take the available literature which is, of course, what is the foundation of the guideline, and we wanted to synthesize all of that into something that was very easily accessible to people. That was part of the reason that we came up with a lot of diagrams and figures that just gives the main points so that a very busy rheumatologist can even glance at a flow chart and just see, "Oh, you know what? This patient has the antiphospholipid. They're thinking of getting pregnant. They've had a clot. This is what I should think about." We really wanted to try and take away some of the work for our rheumatology colleagues and make it easier for them to just dive right in and communicate with the patients and know that they need to be in touch with the OBs as well. Rebecca Mashaw: Thank you very much for spending this time with us today to talked about the guidelines for pregnancy and reproductive health in women with rheumatic diseases. We'll look forward to future conversations as updates come along. Lisa Sammaritano: Thank you for asking me.