patient care perspectives

Women With Rheumatoid Arthritis: Perceptions About Fertility and Pregnancy

by Vibeke Strand, MD, MACR, FACP

Overview

The management of rheumatoid arthritis (RA) in women of childbearing potential involves having conversations about the importance of disease control and of choosing an agent with an acceptable safety profile.

Expert Commentary

Vibeke Strand, MD, MACR, FACP

Adjunct Clinical Professor, Division of Immunology/Rheumatology
Stanford University School of Medicine
Biopharmaceutical Consultant
Palo Alto, CA

“I think that it is important to recognize that the manufacturer of certolizumab pegol has conducted trials in pregnant women and their recently born children, which we all appreciate is almost impossible to do.”

Vibeke Strand, MD, MACR, FACP

Since 75% of our patients with RA are women, conversations about fertility and pregnancy happen all the time, and these conversations are rich with opportunities for counseling. Many women today have delayed pregnancies, and they may not feel confident that they have enough time to become pregnant, can successfully deliver, and/or can have more than 1 child. We need to have conversations about treatment approaches and the importance of monitoring the disease during and after pregnancy. We also need to make sure that, once we decide on a treatment, we are confident that it will control the disease. One of the worst things you could do during pregnancy is to have a flare of disease because that has the potential to be more detrimental to the developing child than the risks from appropriate RA treatment during pregnancy.

Regarding treatment, you obviously do not want to put patients who are likely to become pregnant on either methotrexate or leflunomide because these agents are contraindicated and they have very long half-lives; it takes a significant amount of time to wash these agents out, and that is not what people want to be thinking about as they are trying to become pregnant. Targeted synthetic disease-modifying antirheumatic drugs have short half-lives; however, they are not labeled as first-line therapy.

I think that it is important to recognize that the manufacturer of certolizumab pegol has conducted trials in pregnant women and their recently born children, which we all appreciate is almost impossible to do. Very few companies are willing to conduct a trial in pregnant women or in women who have recently delivered, or even while they are lactating. However, as of 2019, the US Food and Drug Administration has actually put all of the available pregnancy data for certolizumab pegol from these trials in the package label. It essentially says that, because the F(ab)' is pegylated and there is no fragment crystallizable (FcR) portion of the molecule, there is very little transfer of the biologic across the placenta to the fetus. At birth, levels were unmeasurable in the majority of the infants studied and just a couple had very low levels, right around the limits of detection. Data suggest that transfer into breast milk is also low. So, when I talk to patients about pregnancy and we settle on tumor necrosis factor inhibitor therapy, I will start with certolizumab pegol, even if it is going to require a series of prior authorizations and discussions with providers.

References

Balbi GGM, Domingues V, Balbi GGM, De Jesús GR, Levy RA. Use of synthetic and biologic DMARDs during pregnancy. Expert Rev Clin Immunol. 2019;15(1):27-39. doi:10.1080/1744666X.2019.1541739

Bermas BL, Sammaritano LR. Fertility and pregnancy in rheumatoid arthritis and systemic lupus erythematosus. Fertil Res Pract. 2015;1:13. doi:10.1186/s40738-015-0004-3

Birru Talabi M, Eudy AM, Jayasundara M, et al. Pregnancy, periods, and “the pill”: exploring the reproductive experiences of women with inflammatory arthritis. ACR Open Rheumatol. 2019;1(2):125-132. doi:10.1002/acr2.1016

Cimzia. Prescribing information. UCB, Inc. Accessed September 21, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125160s270lbl.pdf

Clowse MEB, Scheuerle AE, Chambers C, et al. Pregnancy outcomes after exposure to certolizumab pegol: updated results from a pharmacovigilance safety database. Arthritis Rheumatol. 2018;70(9):1399-1407. doi:10.1002/art.40508

Flint J, Panchal S, Hurrell A, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55(9):1693-1697. doi:10.1093/rheumatology/kev404

Krause ML, Makol A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol. 2016;8:23-26. doi:10.2147/OARRR.S85340

Kvien TK, Uhlig T, Ødegård S, Heiberg MS. Epidemiological aspects of rheumatoid arthritis: the sex ratio. Ann N Y Acad Sci. 2006;1069:212-222. doi:10.1196/annals.1351.019

Mariette X, Förger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77(2):228-233. doi:10.1136/annrheumdis-2017-212196

Provost M, Eaton JL, Clowse MEB. Fertility and infertility in rheumatoid arthritis. Curr Opin Rheumatol. 2014;26(3):308-314. doi:10.1097/BOR.0000000000000058

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