Please could you give a brief introduction to the different types of drugs used to treat rheumatoid arthritis (RA)?
Prednisone and non-steroidal anti-inflammatory drugs (NSAIDs) can be used for symptom control, but to prevent joint damage, we use disease-modifying anti-rheumatic drugs (DMARDs) including the cornerstone, methotrexate.
Not infrequently, when a patient has side effects to DMARDs, and/or when the RA is incompletely controlled with DMARDs, ‘biologic’ drugs (like anti-tumor necrosis factor, anti-TNF drugs) are used as well.
What are anti-tumor necrosis factor (anti-TNF) drugs and how many women with RA take these drugs?
Anti-TNF agents target an inflammation-causing substance (tumor necrosis factor, TNF) produced by the body’s immune system.
Anti-TNF drugs are used to treat not RA but also other diseases where the body’s immune system is over-active, such as Crohn's disease and psoriasis.
Anti-TNF drugs control inflammation in joints, and hopefully help prevent long-term joint damage, in RA patients who have side effects to DMARDs, and/or when the RA is incompletely controlled with DMARDs.
Anti-TNF medications are expensive (can cost more than $10,000 per year).
In what ways can anti-TNF drugs affect the development of a fetus and how does this compare to other drugs such as methotrexate (MTX)?
Anti-TNF drugs are considered by the US FDA to be in “category B” concerning fetal risk, which means that “no adequate and well-controlled studies have been conducted in pregnant or lactating women”. So, generally avoid exposure to these medications during pregnancy.
Methotrexate however is definitely known to have the potential to cause serious birth defects (including problems with limb and brain development) and complications during pregnancy, noteably pregnancy loss.
How did your research into RA drugs and abortion rates originate?
RA affects upwards of 1% of the general population, and is more common in women than men. It often affects women in their reproductive years.
In women affected with RA during their reproductive years, specific factors, such as drug exposures, may influence a decision to end an unplanned pregnancy.
Although there is considerable information regarding many aspects of pregnancy in women with RA, studies on induced abortion in RA and its potential predictors are scant. Thus, we aimed to determine the rate of induced abortions in women with RA exposed to MTX compared to women with RA unexposed to this medication.
What did your research involve?
We conducted a case-control study using information on 5,967 women with RA, recorded within Quebec’s administrative physician billing and hospitalization records, from 1996 to 2008. We identified 112 cases of induced abortions and 5,855 corresponding RA controls, and compared drug exposures in the cases versus controls.
What did your research find?
The overall rate of induced abortions was 6.78 cases per 1000 person-years. Exposure to MTX occurred in 10.7% of cases and in 21.7% of controls.
Interestingly, women with RA exposed to MTX had a lower rate of induced abortions than unexposed women. Still, induced abortions in women with RA on methotrexate are relatively common, suggesting that pregnancy planning may need to be optimized.
The results also suggested that women with RA exposed to anti-TNF agents are potentially at increased risk of induced abortions compared to unexposed women with RA.
How do you think these results can be explained?
There are several potential explanations…the results might suggest that in fact we are pretty good about warning women with MTX use about need for good pregnancy planning, and/or we may be following them more closely, and/or their disease may be so severe/active that they avoid pregnancy....
What impact do you think this research will have?
This is the first study to document induced abortion rates after diagnosis in women with RA. These results raise potential concerns on the rate of unplanned pregnancies in women with RA, particularly those on anti-TNF agents, and should prompt future research on counselling, contraception use, and unplanned pregnancies in these women.
How can the number of unplanned pregnancies in women with RA taking MTX or TNF inhibitors be reduced?
There needs to be good communication between a patient and her health care providers (including physicians and pharmacists) so that every woman of reproductive age who are taking drugs like methotrexate are aware that she needs to avoid pregnancy while on these drugs.
What further research needs to be done on this topic?
One research need is that more information is required regarding long-term adverse outcomes of children born to mothers exposed to anti-TNF drugs (and other immune-suppressing medications used in RA ----and in similar diseases where the immune system is over-active).
As noted above, there should also be more research on counselling, contraception use, and unplanned pregnancies in women with RA.
Where can readers find more information?
The American College of Rheumatology website includes the following on their patient info page regarding mtx
'Methotrexate can cause serious birth defects and complications during pregnancy, so it is important that you discuss birth control and pregnancy plans with your physician while taking this medication. An effective form of contraception is critical while taking methotrexate and for at least three months after stopping the medication.'
Various guidelines endorsed by professional rheumatology bodies are consistent with this
About Dr Sasha Bernatsky and Dr. Evelyne Vinet
Evelyne Vinet MD FRCPC is a rheumatologist and an assistant professor in the Department of Medicine, Division of Rheumatology, at McGill University. She is currently completing her PhD in the Department of Epidemiology and Biostatistics at McGill. The subject of her thesis relates to reproductive issues in women with rheumatic diseases. Dr. Vinet designed the current study and is the first author. Her research is supported by the Fonds de recherche du Québec, FRSQ, and the Canadian Institute of Health Research (CIHR).
Sasha Bernatsky MD FRCPC PhD is associate professor in the McGill Department of Medicine, Divisions of Rheumatology and Clinical Epidemiology. Her research is supported by the FRSQ, CIHR, NIH, and the Public Health Agency of Canada . Dr. Bernatsky's research has focused on various long-term outcomes in systemic autoimmune rheumatic diseases. Some of her work uses various administrative database sources to evaluate disease burden and outcomes in rheumatoid arthritis and other conditions. Other areas of interest include co-morbidity, the economic impact of rheumatic diseases, and early diagnosis and access to care.