Lisa Sammaritano, MD, on Lupus Nephritis and Reproductive Health: Part 1
In this podcast--the first of 2 on reproductive health care for patients with lupus nephritis—Dr Sammaritano discusses how the rheumatologist can work their female patients with lupus nephritis in selecting contraception and planning for pregnancy.
Lisa Sammaritano, MD, is a professor of clinical medicine and an attending physician in rheumatology at Weill Cornell Medicine and the Hospital for Special Surgery in New York City.
Rebecca Mashaw: Hello, and welcome to another podcast from Rheumatology Consultant.
Today, Dr. Lisa Sammaritano, a professor of medicine at Weill Cornell Medicine and an attending rheumatologist at the Hospital for Special Surgery in New York City, is going to discuss the special challenges that come with working with patients who are pregnant or who wish to become pregnant when they have systemic lupus erythematosus, and particularly when they have lupus nephritis.
RM: Is it true that many more women than men suffer from lupus and lupus nephritis?
Dr Lisa Sammaritano: Absolutely. Many autoimmune diseases have a high female to male ratio, but lupus has one of the highest. For patients of reproductive age with lupus, the ratio of women to men is about 9:1.
The ratio is somewhat lower for childhood onset lupus and onset of lupus in later years. 9:1 is the ratio for the reproductive years, which is when lupus is most commonly diagnosed.
RM: How does this complicate the whole issue of reproductive health for patients with this disease?
Dr Sammaritano: It is an incredibly important area of health for women with lupus. Over the past several years, more and more attention has been paid to this, not only in terms of pregnancy in patients with lupus, which has been looked at for many years and recognized to be a high‑risk pregnancy for these patients, but even in terms of contraception, fertility therapies.
These are areas of reproductive medicine that also can be more difficult or challenging for patients with lupus, depending on the specifics of their disease, their autoantibodies, their clinical status.
Some years ago, I think it was 2016, the European rheumatology group called EULAR published some recommendations for reproductive health in patients with lupus. In 2020, the American College of Rheumatology, our national rheumatology group, published a comprehensive guideline on all aspects of reproductive health for women in lupus, ranging from contraception to fertility preservation and fertility treatment through pregnancy, and including menopause and the question of hormonal replacement therapy for patients.
That was published about 1 year ago now. It has been a good reference and guide for practicing rheumatologists who are honestly faced with these issues all of the time. One of the problems with this particular area is that it is the intersection of 2 specialties in medicine. It's obstetrics and gynecology issues but lupus rheumatology patients.
It's incredibly important that rheumatologists have some understanding of this, because the obstetricians are not lupus doctors and they may not feel comfortable making decisions on their own for our lupus patients. Having some knowledge about this and, of course, collaborating with them for our patients in making the right decisions is incredibly important.
RM: Do you try to work closely with your pregnant patients' OB/GYNs?
Dr Sammaritano: Absolutely. We have done that for many years, starting with Dr. Michael Lockshin, who has been at Hospital for Special Surgery for many years and was one of the first preeminent researchers in the area of lupus and pregnancy. He has been my mentor for many years.
From the time of my fellowship at HSS, I have focused on this, and we have always communicated and collaborated with our OB/GYN colleagues for patient care.
More recently, we formalized this with the formation of a rheumatology reproductive health program, where we have certain maternal‑fetal medicine specialists, we have pure GYN specialists, we have reproductive endocrinologists who work closely with us, not only on patient care but also on ongoing research projects and also on both fellow or resident education and patient education.
We're trying to educate people about the issues, clarify some of these questions, in terms of our own research, and most importantly, optimize our clinical care of these, at times, complicated patients.
RM: In a previous podcast that you did with us, you mentioned that women with rheumatic diseases are less likely to use contraception, and if they do, they often use less effective contraception. Why is this the case, and does this also apply to women with lupus as well as those with other rheumatic diseases?
Dr Sammaritano: That statement is probably most true for patients with lupus. There are a number of reasons, although we can't know for certain.
One issue is that lupus is a complicated disease and visits to the rheumatologist are often focused on ongoing flare or inflammation, sometimes leaving little time for covering other, less urgent issues.
Another issue is that patients with lupus for many years were told not to use estrogen‑containing contraception, including the standard birth control pill. The reason for that is that lupus affects women of childbearing age who have high estrogen levels, at least during part of their cycle. There's long been a concern that estrogen might be driving some of the lupus inflammation.
There were case reports many years ago also suggesting that patients might flare if they took birth control pills, and so birth control pills were off the table for a long time. In 2005, 2 studies were published, one of which I was involved with, called the SELENA study. Both studies found that for patients with quiet, well‑controlled lupus who did not have antiphospholipid antibodies, which are antibodies that predispose to blood clots, that taking oral birth control pills did not increase the risk of flare. That was in terms of the spectrum of use of birth control pills relatively recent.
Finally, rheumatologists don't know a lot about birth control. Most of us don't usually read the OB/GYN literature, and so some rheumatologists aren't aware of the current recommendations for birth control, including the recommendation to use a long‑acting reversible form of birth control as a first option. Those include intrauterine devices (IUDs), as well as subdermal progestin implants. Without encouragement from the rheumatologist, patients may not know that this is OK for them. Their OB/GYN may not know it's OK for them either and may just think, "OK, I don't want to take any chances with causing a flare of lupus. I'm not going to recommend anything. Continue using your barrier contraception," which, of course, is contraception and is effective, but not nearly as effective as either birth control pills or IUDs, these other measures that have much higher efficacy.
It is likely a combination of all of these factors that have limited patients from using the most effective forms of birth control.
Rebecca: Let's add in the fact that lupus nephritis tends to present during the first few years after a diagnosis of lupus. Doesn't that mean that LN is also going to present during those prime years for childbearing? How does that further complicate the care of patients who may want to have children?
Dr Sammaritano: That is a very important point. It is true, and it is one of the biggest challenges that we face for these patients.
Lupus nephritis, when diagnosed ‑‑ and it is diagnosed in up to 50% of patients with lupus at some point during their course, so it's not that it's uncommon or rare —when diagnosed, we treat, usually, for a period of 2 years with induction therapy, the stronger initial therapy to bring that inflammation under control, followed by maintenance therapy, which is ongoing therapy to keep the inflammation under control. That's a 2‑year period of time during which patients should not consider pregnancy and should be using very effective birth control.
I will say that both of our best options for treatment of lupus nephritis are also medications that cannot be taken during pregnancy. Even aside from the risk to the patient of becoming pregnant when disease is active, there would also be a risk of birth defects, teratogenicity, in the baby.
The 2 drugs that are most commonly used are cyclophosphamide and mycophenolate. Cyclophosphamide is also a medication that, while used less commonly now than in the past, can decrease a woman's fertility. That's another important aspect of reproductive health concerns for our patients who do need that particular medication to treat their lupus.
Since more recent studies showed that mycophenolate is as effective for most patients, that's a much more frequently used treatment for lupus nephritis at this time, but again, it is teratogenic. It does require effective birth control, and there are some concerns that it can interfere with estrogen and progesterone in the birth control pill and maybe make it less effective.
There is a REMS program that is basically an informational program for doctors and patients going over the most effective methods of birth control for use with this drug. In general, either an IUD or use of 2 other methods of birth control is recommended.
That's 2 years, more or less, depending on the patient's response, of course. After that, we need to think about how to protect our patients but still hopefully allow them to proceed with their plans for pregnancy. What is usually done is a change to a pregnancy‑compatible medication, azathioprine. That is OK to take during pregnancy and during breastfeeding also.
What we often will do is transition from the mycophenolate to azathioprine, and then again, watch patients carefully to make sure, number 1, they tolerate the azathioprine without side effects, and number 2, that it works for them. It doesn't always.
There was a recent study that looked at this exact issue, looked at patients who had just completed their course of mycophenolate for lupus nephritis and were transferred to azathioprine. For the 4 to 6 months after the change in medication, only 13% of patients flared on azathioprine. For most patients, it seems that is OK, and it will control them.
There is this small percentage of patients where the azathioprine may not be as good for them as the mycophenolate was, and then we need to think about other options.
Rebecca: What about some of the newer drugs? What do we know about their safety for the pregnant patient with lupus nephritis?
Dr Sammaritano: Right now, standard therapy for lupus nephritis is either cyclophosphamide or mycophenolate. The other FDA‑approved add‑on drugs, as of just this past year, are belimumab, which is a biologic medication that had been approved 10 years previously for nonrenal lupus but just recently approved for add‑on therapy, and voclosporin, which, again, was just recently approved as add‑on therapy. These 2 therapies, we don't know that they have an adverse effect. We just don't have the information yet.
There is another drug, tacrolimus. That drug is most commonly used for kidney transplant patients. They routinely continue that drug along with azathioprine throughout pregnancy. We, and others, have used tacrolimus, either in combination with azathioprine or even as monotherapy for patients who need additional meds or a different med during the course of their pregnancy. Again, that drug, like azathioprine, is felt to be compatible with pregnancy as well as with breastfeeding.
RM: Join us for our next podcast with Dr. Sammaritano as she discusses some of the complications that can arise during pregnancy for patients with lupus nephritis, whether active or quiescent, and how to manage those complications.