Grace C. Wright
Individuals with chronic inflammatory diseases continuously fight several adversaries, including pain, loss of functionality and complications due to treatment. Women of childbearing age who wish to start families can add two more opponents to that list: fear and misinformation.
Many of these women mistakenly believe that the choice to have children is fraught with a series of no-win scenarios: Cease therapy and face disease-related complications, or continue therapy and face drug-related harms to the baby. Similar concerns apply to the question of whether to breastfeed. Data answering these questions are only just beginning to emerge, and busy rheumatologists may struggle to keep up. All of these fears make family planning difficult, and lead many women to forego having children altogether.
Like many practicing rheumatologists, Grace C. Wright, MD, PhD, a specialist in rheumatology at New York University Langone Medical Center, sees these challenges firsthand. “Many of my patients are not fully informed about their diagnosis or appropriate treatment options, and many are not prepared to make the most informed decisions before, during and after pregnancy,” she said.
Jeffrey Stark, MD, head of U.S. Medical Affairs in Rheumatology at UCB, and a practicing rheumatologist, suggested one key reason for this phenomenon. “In the United States, a full 50% of pregnancies are unplanned,” he said. “This means that, in many instances, our patients will not approach us to proactively optimize their treatment plan in advance of a pregnancy.”
Wright acknowledged that certain conditions can lead to adverse pregnancy outcomes if untreated, and certain drugs may not be appropriate, but noted that these factors should not necessarily rule out pregnancy. Emerging data support this. Findings from Clowse and colleagues in Arthritis and Rheumatology showed that preterm births occurred in 12% of all live births among women treated with the TNF inhibitor certolizumab pegol (Cimzia, UCB), which the researchers noted is similar to the rate in the general U.S. population. The findings also showed a 9% miscarriage rate and a 1% stillbirth rate, rates that were again similar to those in the general population.
In short, pregnancy, when properly planned, may be a safe option for women with rheumatic diseases. With this in mind, Healio Rheumatology investigated the factors involved in such a decision, including areas where the findings are conclusive as well as those in which questions remain.
Many women with chronic inflammatory diseases believe that the choice to have children is fraught with a series of no-win scenarios.
Understanding the epidemiology
Studies that answer — or at the very least, ask — these questions are beginning to emerge. One such data set is the Auto-Immune Motherhood (AIM) survey, which was funded and conducted by UCB. The survey included 1,052 women of childbearing age — defined as 18 to 45 years — from the U.S., European Union and Japan who had rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, or other chronic inflammatory diseases. Results showed that 44% of women in the U.S. group delayed pregnancy due to concerns associated with their disease. Treatment discontinuation while planning or at the start of their pregnancy was reported in 36% of U.S. women. However, despite these concerns, only 41% of U.S. women sought consultation from a health care professional about these issues.
Wright is enthusiastic about her participation in AIM, and the goals it can achieve. “It aims to help these women learn the facts about their conditions, share their experiences to empower one another, and guide them to work with their doctors to combine family planning and disease management early in their family planning journey,” she said. “It can be a very effective supplement to ongoing consultation between rheumatologists and their patients.”
For Stark, one of the most important factors to consider is the risk posed by uncontrolled disease vs. risks posed by taking medications. “Ensuring adequate disease control and discontinuing inappropriate medications prior to conception are important measures to ensure a healthy and successful pregnancy,” he said. “Patients quite rightfully often desire to minimize their medication during pregnancy and breastfeeding. However, in many instances, this decision is based solely on the risks of the medication involved without due consideration of the negative effects of disease activity on pregnancy outcomes. To make a truly informed decision, patients must consider not only the risks of therapy, but also the risks of active inflammation for their developing infant.”
Wright offered concrete examples of this. “Active RA, as well as Crohn’s disease, during pregnancy can have serious implications for both mother and infant,” she said. “These implications include increased risk of miscarriage or preterm delivery, the need for a cesarean, and the infant being small for gestational age.”
Before and after birth
This raises the issue of whether the drugs women take to treat their condition will impact their fetuses. Mariette and colleagues conducted the CRIB study to assess whether certolizumab crossed the placenta in a cohort of 16 pregnant women. Results published in the Annals of the Rheumatic Diseases showed no placental transfer in 13 of 14 infants with follow-up data for blood samples taken post-delivery.
“For many years, awareness of these data regarding placental transfer was greatest in the gastrointestinal medical community,” Stark said. “The inclusion this year of these data in the approved Cimzia Prescribing Information through the FDA’s Pregnancy and Lactation Labeling Rule — as well as similar additions to the label by the European Medicines Agency — has helped to make them more immediately available to rheumatologists.”
“Professional guidelines are a separate and important discussion, and physicians should also remain current on the latest research and regulatory developments affecting appropriate treatments for their patients throughout their lives,” Wright added.
According to findings presented at EULAR 2018 by Tincani and colleagues, among women with chronic rheumatic disease who participated in the AIM survey, 22% who were treated with these drugs voluntary decided to discontinue treatment during pregnancy, while 47% were advised to cease treatment by a health care professional. In another study by the same group, researchers found that American physicians were more likely than their European counterparts to prescribe TNF inhibitors to women during and after pregnancy.
“While pregnancy outcomes data exist for multiple biologic agents, new research is needed to understand long-term repercussions of biologic exposure during pregnancy,” Stark said. “Additional research over longer periods of time will shed light on issues such as the attainment of developmental milestones and safety of vaccinations for infants born to biologic-treated mothers.”
Post-childbirth, breastfeeding is another area of question for many women with rheumatic diseases. While 89% of women with chronic rheumatic disease in the Tincani cohort discussed breastfeeding with a health care professional, 66% reported that they believed they had to choose between continuing treatment and breastfeeding.
“This research confirms what I have seen in my own practice: women need to be encouraged to work with their physicians during these special times,” Wright said. “With AIM, we hope to help these women learn the facts about their conditions and work with their doctors to combine pregnancy planning and disease management early in their family planning journey.”
The role of the rheumatologist
Part of the reason for misinformation is that only 46% of the women in the Tincani study had even visited a health care professional prior to becoming pregnant, and just 53% of those women had consulted a rheumatologist. Moreover, 69% of patients from this group who visited a health care professional before pregnancy had to initiate the discussion themselves on topics related to pregnancy and childbirth.
This raises the question of whether rheumatologists require more formal training on these topics. “Each rheumatologist should ask himself or herself this question,” Wright said.
As data continue to mount, keeping pace with the latest research may be no easy task for a busy rheumatologist, according to Stark. “As the FDA phases out the previous pregnancy risk letter categories — A, B, C, D and X — rheumatologists must become familiar with greater volumes and depths of data on issues such as pregnancy outcomes, placental transfer and breast milk transfer,” he said. “In addition, multiple professional organizations, including the American College of Rheumatology, are developing guidelines to help inform the care of women with rheumatic diseases. Training and educational initiatives will be necessary to build the expertise of the rheumatology community on these and other key topics.”
However, Stark suggested that training may force many rheumatologists to rethink years of study and practice. “Although recent cohort data demonstrate the burden of active disease during pregnancy, rheumatologists have been classically taught to expect spontaneous improvement in disease activity during pregnancy,” he said. “This false expectation may lead rheumatologists to undertreat patients during pregnancy; the resulting disease activity may lead to joint damage and increase the likelihood of negative pregnancy outcomes.”
Tincani and colleagues also reported that while 68% of the cohort reported seeing a rheumatologist among other health care professionals, 65% had a treatment plan that was created across health care specialties. Although rheumatologists play a critical role in guiding patients through motherhood, they should not be expected to do it alone, according to Wright. “Even the most committed rheumatologist and sincere patient needs a larger care team for support,” she said.
For Stark, coordinating with other health care professionals is critical. “As disease state experts, rheumatologists play a central part in coordinating the efforts of the entire care team,” he said. “Key members of this team, such as the obstetrician, primary care physician and pediatrician, may benefit from our guidance on issues such as pharmacologic treatment, disease and pregnancy monitoring, vaccination of the neonate, and postpartum follow-up.”
He added that clinicians are not the only group involved. “Patient advocacy groups have taken measures to make patients aware of this information,” Stark said. – by Rob Volansky
For more information:
Jeffrey Stark, MD, can be reached at 1950 Lake Park Dr. SE, Smyrna, GA 30080; email: email@example.com.
Grace C. Wright, MD, PhD, can be reached at 345 East 37th Street, Suite 303C, New York, NY 10016; email: firstname.lastname@example.org.
Clowse ME, et al. Arthritis Rheumatol. 2018;doi10.1002/art.40508.
Clowse ME, et al. Ann Rheum Dis. 2017;doi: 10.1136/annrheumdis-2017-211384.
Mariette X, et al. Ann Rheum Dis. 2018;doi: 10.1136/annrheumdis-2017-212196
Tincani A, et al. Abstract #0693. Presented at: EULAR Annual Congress; June 13-16, 2018; Amsterdam.
Tincani A, et al. Abstract #0692. Presented at: EULAR Annual Congress; June 13-16, 2018; Amsterdam.
Thyssen N, et al. WoCBA Patient Survey Key Topline Findings. Questionnaire. 16 Nov. 2017.
Thyssen N, et al. WoCBA Patient Survey Raw Data. Questionnaire. 16 Nov. 2017.
Disclosures: Stark reports being a full-time employee of UCB. Wright reports receiving compensation for time spent participating in the AIM project, she is doing so because she believes the AIM movement is an important initiative to help serve women with chronic inflammatory diseases.