Pregnancy and RA: Meta-analysis of 120 Research Studies

Taken from NRAS magazine, Winter 2011

This brief outline highlights the significant meta-analysis (wide ranging review of all relevant literature) of 120 scientific research and observational studies. The comprehensive article was written following the Spring Lecture Sessions on pregnancy and immune driven inflammatory disorders by members of the Academy of Immunology for Clinicians in Belgium.

The aim was to provide the most up to date evidence to guide consultants and other health professionals in safe, effective, timely and sound management of those with RA wishing to embark on pregnancy, maintain a viable pregnancy to term, deliver a healthy infant and successfully breast feed.

It has been known since 1938 that the symptoms of RA often improve during pregnancy and that these may flare up within a few months of the birth of the baby. Why this happens is still not known.  The  improvement seen in pregnancy is not reflected in any changes in anti-CCP or rheumatoid factor (RF) levels.   Improvements in pregnancy may be more significant for anyone whose tests for anti-CCP and RF are negative. It is possible that the effects of changing hormone levels, particularly oestrogen and progesterone are involved as well as increased levels of cortisol and vitamin D. It is very likely that these hormones and vitamin D lower the inflammatory chemicals consequently improving the RA symptoms.

In patients with RA, a flare up after giving birth has been linked to the rise in the prolactin hormone levels in breast feeding mothers. This is not to suggest that breast feeding might influence the risk of developing RA as a new diagnosis.  There are studies that have shown that breast feeding may give protection from the possibility of developing  RA in the future. This situation remains unclear.

The in-depth article has reported in detail the evidence around drug management. It is not possible to test the safety of drugs for use in pregnancy because it is unethical. The consequence of this is that possibly harmless drugs may be classed as unsuitable because there is no information to say they are safe to use.

Rheumatology Consultants have to balance the management of the patient’s RA with the need to protect the unborn child from potentially harmful drugs. For drugs that have been in use for decades, the evidence will have grown up over the years that they are either safe or not. Methotrexate and Leflunomide must not be used before or during pregnancy and need to be stopped well in advance (advice from your consultant is imperative especially for leflunomide).  Hydroxychloroquine, sulfasalazine and azathioprine are all suitable drugs during pregnancy if the RA needs this level of control.  Additionally, steroid treatment up to a maximum of 15mg daily oral dose is acceptable.  Anti-inflammatory drugs can only be used in the first half of pregnancy but specific advice on which drug and the dose is important.

At present there is very little information on the use of anti-TNF (biologic) therapy either before or during pregnancy. For those with aggressive disease (and based on the evidence from the treatment for inflammatory bowel disease) anti-TNF therapy is considered to be safe particularly when a balance has to be found between the control of the arthritis and any potential harm before and during the early weeks of pregnancy.

“The clinical management of pregnant RA patients suffers from the wide gap between formal safety data and the need to make therapeutic decisions for adequate disease control in daily clinical practice”

From: Rheumatoid and pregnancy: evolution of disease activity and pathophysiological considerations for drug use. Hazes et al:  Rheumatology 2011; 50: 1955 - 1968