RA Meds And Pregnancy

Leslie Rott Health Guide
  • No, I'm not pregnant (Don't worry, Mom. You'd be the first to know). But before that, most people would ask who the guy is (Minor details, people, minor details). But the reality is, while I don't have a man or a baby, it's a topic that is at the forefront of my mind. Why? Well, because the way I figure it, if I'm 26, and I meet someone and date them for a year, and then we get engaged for a year, and then get married, and then I have to be off of meds for at least six months, by the time I'm (at the earliest) ready to have a baby, I'll be pushing 30 years old.

     

    And by then, who knows? Will my drug battered body (specifically ovaries) have any juice left in them? Survey says...

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    About a year and a half ago, when I thought I had met the person who I truly thought was "the one," I went to my rheum, asking what pregnancy would look like for me. My rheum wasn't too happy with the "hypothetical" situation, but I wouldn't back down. I needed to know. And at the time, it didn't seem all that hypothetical. Basically, his response was that I would need to be off of all meds other than Prednisone, for at least six months. Now that presupposes the fact that I can actually get off meds and be able to function to some extent. I really wanted to give it a try. But my rheum would have none of that.

     

    The reality is, while some women seem to go into spontaneous remission during pregnancy, some still have disease activity, and some end up with a severe flare after the baby is born (1,2). I'm not sure it's ever a simple decision to have a baby, but for women with RA and other autoimmune conditions, it's no simple matter. It probably ends up being one of the most planned, least spontaneous events in ones adult life.

     

    The few things that are clear are: 1) You should be medication-free, other than

    Prednisone basically, for at least six months, and possibly a year, before conception, 2) Any pregnancy where there are comorbidities of any kind is going to be high risk, and 3) Prednisone is the medication of choice during pregnancy, and I guess if you are going to be fat and moody anyway, might as well embrace it.

     

    So that's the vague idea, at least for me, with the background that Methotrexate was used as an abortion drug in the 1950s and Quinacrine has been used for the forced sterilization of women in third world countries (3). This doesn't provide confidence that, even getting off of meds, pregnancy would be an easy thing. But that's a whole other issue, and while infertility can be an important issue for those with chronic illnesses, like RA, it's not something I'm going to address in more detail here, other than how it relates to medication and pregnancy.

     

    The main types of medications used for the treatment of RA are Nonsteroidal anti-inflammatory drugs (NSAIDs), Corticosteroids, Disease-modifying antirheumatic drugs (DMARDs), and biologics (4). As NSAIDs and Corticosteroids can be taken during pregnancy, my focus here will be on DMARDs and biologics.

     

  • I poured through the package inserts for many of the drugs used to treat RA (and occasionally lupus, too) - Actemra (5), Enbrel (6), Humira (7), Orencia (8), Remicade (9), Rituxan (10), and Simponi (11) - and the conclusion was the same: it's too soon to tell if these drugs are safe during conception and pregnancy. So in other words, take them at your own risk.

     

    More detailed information about drugs and pregnancy risk were available for some drugs, so I've tried to provide a comprehensive review here, while not getting too technical:

     

    Arava

     

    According to the package insert: "Pregnancy must be excluded before the start of treatment with ARAVA. ARAVA is contraindicated in pregnant women, or women of childbearing potential who are not using reliable contraception" (12).

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    There is also a special drug elimination program, without it, it can take up to two years to have undetectable levels of tetratogenic agents.

     

    Benlysta

     

    The best the package insert can say is: "Women of childbearing potential should use adequate contraception during treatment with BENLYSTA and for at least 4 months after the final treatment," however the use of Benlysta in pregnant women has not been studied (13).

     

    CellCept

     

    According to the package insert for CellCept: "Female users of childbearing potential must use contraception. Use of CellCept during pregnancy is associated with increased risk of pregnancy loss and congenital malformations" (14; emphasis in original).

     

    CellCept is known to cause harm to fetuses in women who are pregnant. Such harm includes ear and facial deformities and other abnormalities of the internal organs. Contraception should be used at least four weeks before starting CellCept and at least six weeks after stopping the drug.

     

    Methotrexate

     

    Unlike other drugs, there has been much research when it comes to MTX and pregnancy. The main issue with MTX and pregnancy is that MTX depletes folic acid, and folic acid is required for normal fetal development. MTX demonstrates significant teratogenicity. Skull and limb abnormalities are most frequent (15).

     

    One article states that: "There is thus a theoretical risk of fetal exposure in babies of mothers who have taken the drug up to 4 months prior to conception" (15). The article further catalogues what can only be described as a scary constellation of problems with babies conceived after treatment with MTX. However, the article concludes that "In the study overall, there was a slightly higher but statistically insignificant incidence of stillbirth and congenital abnormality compared to the expected background rate" (15). It is suggested by those authors that conception occur no sooner than one year off of the drug.

     

    The risk of infertility appears low, even after high-dose MTX. According to one article, there is a 97% rate of conception after one or more years after MTX treatment is completed (15). The article goes on to say that while "MTX treatment is unlikely to have a major effect on short- or long-term fertility in men and women, but a washout period of 6 months cessation of treatment prior to conception is advisable to prevent the small chance of chromosomal abnormalities in offspring" (15).

  •  

    While in the cases of some drugs, effects during conception, pregnancy, and breastfeeding are known, in the majority of cases, there are still a lot of questions about safety and efficacy that need to be answered. Questions remain about Anti-Tumor Necrosis Factor (TNF) therapies (16). MTX and biologics are strongly recommended against use during pregnancy (2).

     

    To give bit more of a science lesson, the Food and Drug Administration has category classifications for medications and pregnancy. They are A - "Controlled studies show no risk," B - "No evidence of risk in humans," C - "Risk cannot be ruled out," D - "Positive evidence of risk," X - "Contraindicated in pregnancy," and N - "Not rated." MTX falls into the X classification, while Hydroxychloroquine and Corticosteroids fall under the C classification.

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    Many of the articles I read on the subject suggest that women of childbearing age should strongly consider the treatments they use based on their desire to have children. It seems to me, however, that in practice, drugs are prescribed to treat RA with very little concern about future fertility and risk of fetal harm.

     

    I don't know about you, but I've heard stories about women diagnosed with cancer who have their eggs frozen before they start chemotherapy in order to preserve them for later use (17). I've never heard about this with women that have RA or lupus, though. And I wonder why. Thinking back to my diagnosis, if someone would have brought this to my attention, would I have been as cognizant about it as I am now? At 22, would I have been able to give serious thought to my potential future children? I can't really answer this question because I can't go back. And I can't go back on the years of medication that I've exposed my body to. And right now, I feel pretty good. I'm functioning. So should I question something that's working? Will feeling good be enough if it turns out that when I'm ready to have children, I can't?

     

    To be honest, I'd love to hear from some women who have successfully gotten pregnant with RA or lupus or both. Because all of these medical articles and package inserts don't fill me with a whole lot of confidence. I know it happens, but I'm in need of some reassurance. Oh, yeah, and a man...

     

    References

     

    (1) A. Makol, K. Wright, and S. Amin. (2011). "Rheumatoid Arthritis and Pregnancy." Drugs 71 (15): 1973-1987.
    (2) R. Partlett and E. Roussou. (2011). "The Treatment of Rheumatoid Arthritis During Pregnancy." Rheumatology 31: 445-449.
    (3) J. Zipper and E. Kessel. (2003). "Quinacrine Sterilization: A Retrospective." International Journal of Gynecology and Obstetrics 83 (Supplement 2): S7-S11.
    (4) http://www.arthritistoday.org/conditions/rheumatoid-arthritis/ra-treatment/ra-medications.php
    (5) http://www.gene.com/gene/products/information/actemra/pdf/pi.pdf
    (6) http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf
    (7) http://www.rxabbott.com/pdf/humira.pdf
    (8) http://packageinserts.bms.com/pi/pi_orencia.pdf

  • (9) http://www.remicade.com/remicade/assets/med_guide.pdf

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    (10) http://www.gene.com/gene/products/information/pdf/rituxan-prescribing.pdf
    (11) http://www.simponi.com/sites/default/files/pdf/medication-guide.pdf
    (12) http://products.sanofi.us/arava/arava.html
    (13) http://www.hgsi.com/images/Benlysta/pdf/benlysta_pi.pdf
    (14) http://www.gene.com/gene/products/information/cellcept/pdf/pi.pdf
    (15) M. Lloyd,M. Carr, P. McElhatton, G. Hall, and R. Hughes. (1999). "The Effects of Methotrexate on Pregnancy, Fertility, and Lactation." Q J Med 92: 551-563.
    (16) C. Roux, O.Brocq, V. Breuil, C. Albert, and L. Euller-Ziegler. (2007). "Pregnancy in Rheumatology Patients Exposed to Anti-Tumour Necrosis Factor (TNF)-α Therapy." Rheumatology 46: 695-698.
    (17) http://articles.nydailynews.com/2011-02-05/local/28534694_1_egg-freezing-fertility-clinic-cancer-treatment

Published On: January 18, 2012