RheumNow Podcast - ACR Reproductive Health Slides (9-11-20) Save

It's 09/1120 '20. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. It's 09/11, an important day in American history.

Condolences to families and those affected by that tragedy, and think about how great our country has been in rallying around that tragedy. We need that kind of strength for the future. Today, we're gonna talk about the 2020 ACR guidelines on reproductive health and management of pregnancy issues in patients with rheumatic disease and musculoskeletal disease. These guidelines were, established in 2019. I was part of the committee along with a large number of rheumatologists and patients who met on multiple occasions.

And, you know, congratulations from, to Lisa Samaritano and all of her colleagues and all the hard work they did in this gargantuan task of reviewing the literature, you know, thousands of papers distilled down to 289, studies that were that formed the evidence for the 132 PICO questions and 12 clinical practice guidelines that they came up with. I'm gonna review those for you today. I would encourage you to go to the website either on this report or on the daily download. You can download I think we have six or seven slides on this that you could use in your teaching on, pregnancy and musculoskeletal health. Number one caveat is that these guidelines were largely expert opinion.

Many of the hardest questions we have about the safety of certain medicines in and around pregnancy are unknown and inferred by case reports, registries, actually the clinical trials and drug development for a new drug. There's not a lot of data, but, again, luckily we had a large number of real experts in the field, including, people from the OBGYN field, and again, So, realize that a lot of this is expert opinion. There are several of the statements that we put forth that were strongly recommended based on good evidence. Unfortunately, they were a minority here. I'll refer you to the paper to get the weighting, if you're stuck in trying to figure out how strong you should consider this.

Let me give you a few caveats to begin with. Number one, the guideline committee felt it was important that women with rheumatic disease who are pregnant be managed comanaged by a rheumatologist and other experts as need be to manage that patient. That may include maternal fetal, you know, health experts, you know, high high risk OBGYNs when appropriate. Second, that, in your being involved as a rheumatologist, you should also be monitoring disease activity during their pregnancy. They didn't go so far as to say how many times you should see the patient and at what schedule, but that you should be monitoring disease and that may include laboratory testing to, be checked at least once every trimester during pregnancy, and really, you know, use that as the basis to educate the patient along the way.

Again, it's important to do these in women who want to conceive and especially when considering medicines that could, affect their disease activity and or their fertility for the future. Women who are inadvertently exposed to teratogens during pregnancy, they strongly recommend discontinuing the medication and refer the patient to maternal fetal medicine, for consultation and future action. It is need not be that all of them end up with elective abortions. Many of them can carry. And there's good data, observational data I should say, on pregnancies conceived on leflinamide and methotrexate where most, the vast majority of them were normal pregnancies.

So again, you need to work with a maternal fetal medicine specialist to know, really how to manage that and the patient usually wants that. And then lastly, women should be encouraged to breastfeed, if that's desirable and medically possible. Disease control, should be maintained with medications that are compatible with lactation. I'll review that at the end. Turns out that most of our medicines are compatible with breastfeeding, but this needs to be reviewed with the patient.

One of the first slides talks about contraception. It's very important that when you have a woman with childbearing potential, if not at the first visit, At the second visit, ask them what your plans are for pregnancy in the future. How many children have you had? How many do you wanna have? What's your misgivings or issues or concerns?

And you need to educate them about this. The interesting thing about this ACR guidelines and recommendations document, it is dense with information. It is almost it is required reading for every rheumatologist to go through, especially if you're gonna be counseling your patients about what to do regarding future pregnancy issues. And that starts with counseling about family planning and or the use of contraception. Contraception is very important and maybe even more important when you're going to use medicines that have teratogenic potential, especially mycophenolate, cyclophosphamide, maybe even methotrexate and leflinamide.

So it's important to do that. Overall, the guidelines committee recommended IUDs and progestin subdermal implants over hormonal contraceptives. The issue with hormonal contraceptives, of course, is that they impose their own risks including higher risk for venous thromboembolic events, especially people with such a history or in, patients with lupus and anti phospholipid syndrome, etc. Overall, the most highly effective of the contraceptive methods that the committee reviewed were copper IUD, the progestin IUD, and the progestin implant. Almost as effective but not quite would be the progestin only pill given daily.

Depo Provera DMPA I'm injection usually given every three months. The combined estrogen progesterone pill are usually a daily pill. A transdermal patch, could be weekly or a vaginal ring, which can be monthly. And then less effective and frowned upon, if that's your method, would be the diaphragm, the condom. Fertility awareness, methods, that's like, you know, I guess, basal body temperature and other hocus pocus that generally has got all kinds of problems with it, and the use of spermicides.

Specifically, when talking about contraceptive, contraception, you have an active moderate to severely active lupus or lupus nephritis patients. They recommend, using a progestin only medicine, progestin pill, progestin implant, or Depo Provera, or an IUD, and they do recommend against the use of combined estrogen progestin contraceptives. If you have a patient who has the antiphospholipid syndrome, then they do recommend again, IUDs and progestin only, contraceptives, but not again the estrogen progestin pills. So let's move on and talk about something that we don't talk about a lot about, and that is paternal considerations, the fathers of women who are going to get pregnant. And the father has a rheumatic disease, and he's taken all the drugs that you use, and how do you counsel him?

Turns out it almost he can almost take everything that, you know, you don't we we we because we're concerned about that, but most of the data on DMAR and biologic use in the husband seems to have no effect on what happens with, the woman's ability to conceive and have a normal pregnancy. So nonetheless, men who are planning to father a child, need to have the discussion with you about that. And and again, this is so this is not only a women thing. There are your men who are married and and and have a partner that is a reproductive age. This is a conversation you need to have.

And again, are certain medicines that they should know about that will affect their fertility that would include cyclophosphamide and to some extent sulfasalazine. Medicines that are okay to use with a strong recommendation from the committee were hydroxychloroquine, azathioprine, six mercaptopurine, all the TNF inhibitors, infliximab, etanercept, adalimumab, galimumab, cerdulizumab, and even colchicine. Okay to con to continue during the pregnancy or even start, in a father where there's pregnancy around would be they can continue to take leflinamide and or mycophenolate, COX-two inhibitors, nonsteroidal sulfasalazine, cyclosporine, tacrolimus, anakinra, and methotrexate. Not okay. Drugs that should be discontinued or avoided in fathers who may father a child would be cyclophosphamide and thalidomide.

Okay? So the real big issue is women who want to get pregnant and how you advise them. There's a lot written in here. You have to read it. But let's suffice and go straight to the the bottom line here.

If you're planning a future pregnancy or currently pregnant, what's the story with nonsteroidals? First, you don't use a nonsteroidal in the third trimester. Third trimester could cause premature closure of the ductus arteriosus, and that would be a bad thing for the baby. If you're pregnant, it is okay to use a nonselective NSAID, and that is preferred over a COX-two inhibitors. COX-two inhibitors seem to have more of a risk associated with them.

So diclofenac, naproxen, ibuprofen, the nonselective nonsteroidals are preferred. If someone's having a problem conceiving, then it is recommended if you can to stop nonsteroidals as maybe they're getting in the way here. Although there's not a lot of good data, it seems like a simple maneuver one can use for someone's having trouble getting pregnant. Drugs that are safe to use by the mother, leading up to pregnancy and pregnant, would be hydroxychloroquine, sulfasalazine, six mercaptopurine, azathioprine, colchicine, cyclosporine, and tacrolimus. Drugs to avoid in people who want to get pregnant or who are pregnant would be methotrexate, mycophenolate, thalidomide, and cyclophosphamide.

Again, the most dangerous of all these drugs that we use is probably mycophenolate and that is not really appreciated by most rheumatologists. Tend to think methotrexate and leflinamide as being the bad players, not so much. Now clearly are drugs that have problems and should be avoided. But as I said earlier, are a number of people who have conceived on those drugs. The real bad players would be the cytotoxic cyclophosphamide.

Thalidomide, we certainly know about what that does, but also mycophenolate. Mycophenolate is probably the most commonly used teratogen that we use and you need to keep that in mind. You should be off mycophenolate for at least six weeks prior to conceiving. The data on methotrexate is mixed. The committee, came up with a guideline, you should be off of that for three months, which is what everybody thinks.

But in fact, the package insert for methotrexate says you should be off of it for four weeks. So I recommend four weeks, guidelines committee recommend twelve weeks. You should probably go with the guidelines committee. What about biologics? It's, they obviously prefer the use of cerdulizumab because it doesn't cross the placenta.

It's less likely to cause problems in and around the time of of birth, but it is okay to be on a TNF inhibitor prior to pregnancy or while conceiving and even up until the time of delivery. Recent data, not in the guideline, recent data says probably continuing during the pregnancy might be better than stopping once they find out they're pregnant. And it's okay certainly to take that when you're breastfeeding. They do recommend that non TNF biologic agents, avatarsop, tocilizumab, and then belimumab and other biologics, they do recommend you continue those, up until conceiving but stopping them during the pregnancy mainly because very little is known. Rituximab, same thing.

They do recommend continuing up until the time of conception but then stopping but they do say the patient has severe life threatening, organ threatening disease including like lupus nephritis. It may be wiser to continue the rituximab throughout the pregnancy. There is no recommendation because of a lack of data on the use of JAK inhibitors and aprimolase, the small molecule, targeted therapies because again, there's just no data. Now there is data and you can look it up and find out what to do. The bottom line with all these drugs pregnancy is that while we worry about the drugs, the real culprit here in bad pregnancy outcomes is the mother who's got active disease with a lot of inflammation and is uncontrolled.

Maternal inflammation will hurt the pregnancy and the baby much more than any of the drugs you use. First order of business is control of disease activity, whether it's RA, PSA, lupus, gout, patients getting pregnant, it's possible. But control of this activity is your number one thing and we listed for you the drugs that are safe to use here. Lastly, we're going to just talk about lactation and drugs. What I learned through this exercise is that you can pretty much use everything.

You know? So compatible with lactation would include nonsteroidals, hydroxychloroquine, colchicine, sulfasalazine, Biologics, all of them compatible with lactation because, again, they're all given parenterally. Very little of it ends up in breast milk. What ends up in breast milk is gonna be chewed up by the infant's gastrointestinal tract and not get absorbed into the infant. And up to twenty milligrams a day is okay with lactation.

The committee did recommend, breastfeeding if you're on leflinamide, mycophenolate, cytotoxin, methotrexate, and thalidomide. They did recommend, breastfeeding if you're taking more than twenty milligrams per day. But if you are and you need to breastfeed, you take your steroid twenty, thirty milligrams a day. You wait four hours before you, feed the child, through lactation, or you discard the first four hours of breast milk and then use it after that. So within four hours of taking a pill, can show up in breast milk.

You want to avoid that going forward. Anyway, you can go to our website and download slides on this. You can go to our daily download on our homepage or on our email and get the link. You have to sign in to get that. Again, can't underscore enough the one caveat that I've learned throughout this whole exercise, is control of maternal disease activity is paramount.

It trumps everything else. You might be worried about a biologic and what you don't know, but I've used most of these drugs. I don't use mycophenolate, cytotoxin, thalidomide, but I've used, all these drugs in people who are pregnant, and including after the first eight weeks of organogenesis, you could start almost any drug including Cytoxan. I'll refer you to a literature that's not covered here in the oncology world where women who are getting cytotoxic chemotherapy conceive children and deliver normal children. So chemotherapy is not out of the question in women who want to get pregnant and have a child.

There's a lot to be learned here. Look this paper over. It is required reading. Again, be sure to go to our website and, make your comments at, BackTalk, and we'll take your comments and questions next week. Take care.