Why choose RA pregnancy as our field of research?


The fact that RA can improve naturally during pregnancy is a huge deal. Even if it does not happen in ALL women, still, it does happen! And when it does, it is regarded like a miracle of nature … These observations made me wonder: If we could mimic the beneficial effects of pregnancy on RA, would we be able to treat RA with minimal side-effects or even cure the disease? Given that currently available medications have serious side effects, mimicking the effect of pregnancy to alleviate RA symptoms would be highly advantageous. Unfortunately, why RA improves (or gets worse) during pregnancy, and why it flares after child-birth, is still unknown. Although hormonal changes during pregnancy may seem to be an obvious benefactor, they do not explain why RA improves in many, but not all, women with RA. Nor do increased levels of cortisol as Dr. Hench had thought.

Not much is known about what happens during pregnancy in RA. This field of research has not been thoroughly explored. As it turns out, finding women with RA to participate in pregnancy research has been an especially difficult task, not because they did not want to participate, but because researchers did not know how to find them in large enough numbers for research results to be meaningful. On top of that, research participants would need to be enrolled before pregnancy so that changes occurring from “before” to “during” pregnancy can be observed and understood – and that has been an even more daunting task!

This was all the more reason to start my research in this area. On the one hand, there was a high risk that enrolling women in a study at the pre-pregnancy stage could be extremely difficult, if not impossible; this would not be good for my scientific career. On the other hand, I chose to be in the field of RA research because I wanted to help people who, once affected with RA, bear the painful consequences of this disease for life. Should it not be our moral obligation to seize the opportunity to solve this mystery (of why RA improves during pregnancy) – or at least try our best – if doing so meant that we could uncover new knowledge that could potentially give people with RA a more comfortable life? Well, it wasn't a hard choice. And a good challenge is always welcome :)

Improvement: how much? for everyone?

Extent of improvement
Women with RA are well-acquainted with the natural pregnancy-induced improvement of the disease. Those who have experienced it describe it as being “better than any known medications for RA”. However, the extent of improvement appears to vary from one person to another, as reported by patients. Unfortunately, the beneficial effect of pregnancy is only temporary and is followed by a predictable flare of the disease 3-6 months after child- birth.

Not all women experience an improvement
It should also be noted though that not all women with RA experience an improvement during pregnancy. Following Dr. Hench’s 1938 paper, there have been numerous publications reporting that approximately 75-90% of women with RA experience a natural improvement during pregnancy. More recently, one study in the Netherlands found that the proportion of women with RA who go into remission during pregnancy is much lower – closer to 50%. Among the women who do not improve, the disease remains unchanged or may even get worse during pregnancy.


RA and pregnancy

While reading through the scientific literature on RA (before we started our own project), I was struck by the fact an incurable and disabling disease like RA could improve naturally during pregnancy. This meant that while existing medications were associated with serious side effects and were ineffective in up to 30% of patients, “nature” had a way of making women with RA feel all better during pregnancy, without any side effects! This natural improvement of RA was studied and first reported in 1938 by Dr. Philip Hench, who proposed that it could be due to an as yet unidentified “anti-rheumatic Substance X” being produced during pregnancy. Dr. Hench’s research later led to the discovery of corticosteroids as a treatment for RA, a discovery for which he shared the Nobel Prize in Physiology or Medicine in 1950. Here is a copy of his 1950 Nobel lecture. However, it was later found that corticosteroids do not explain the natural improvement of RA during pregnancy. Today, almost 78 years (!) after Dr. Hench’s first paper was published on the topic, the identity of the mysterious pregnancy-induced anti-rheumatic substance X still remains unsolved...