Brindusa Truta
Brindusa Truta

Oral 52 Potential Risks of Immunosuppressant Drugs to the Pregnant Patient

Author Insight from Brindusa Truta Johns Hopkins University School of Medicine, Department of Medicine

What’s new here and important for clinicians?

The treatment of chronic autoimmune disease in pregnancy represents a challenge for many providers. The drugs shown to have therapeutic benefit, such as the biologics and immunosuppressant medications (mainly thiopurine), have potentially negative, long-term effects on babies who undergo intrauterine exposure to these drugs.

We have learned that the most important factor in the pregnancy outcome, at least for inflammatory bowel disease, is the activity of the disease: as long the disease is in remission, a pregnant woman with IBD has a similar risk for preterm birth, intrauterine growth retardation, small for gestation and stillborn baby as a pregnant woman without IBD.  Therefore, maintaining remission is the goal of any provider involved in the care of IBD, and  this goal justifies the use of more aggressive therapy (biologics, thiopurine) if needed.

Despite the reassurance given by the results of the PIANO study, which focused on 1,000 IBD pregnancies treated with immunosuppressive drugs and showed that use of biologics (anti-tumor necrosis factors) and thiopurines is not associated with an increased risk of poor outcomes in pregnancy, many women discontinue the medications because they are concerned about the long-term effect of the medications on the baby.  If the disease relapses and the patient becomes symptomatic, corticosteroids are preferred as a “safe” alternative to conventional therapy.

For this reason, we aimed to investigate the risk associated with the use of thiopurines, biologics and steroids in pregnancy, and we performed a retrospective analysis of 1,134,964 pregnant women registered with the Truven Health Analytics MarketScan database from January 2010-December 2012.

Over 20, 000 (21,457) pregnant women were exposed to these medications: 522 were exposed to anti-TNF (infliximab, adalimumab and certolizumab), 317 to thiopurines, 47 to both (anti-TNF and thiopurines) and 20,422 to steroids (orally or intravenously). Six thousand, five hundred eighty-six  pregnant women had IBD and 1,391 of these were exposed to immunosuppressive drugs, including steroids.

The use of anti-TNFs or thiopurines was found to be safe and not associated with an increased risk of poor outcomes, e.g. intrauterine growth retardation (IUGR), stillbirth or puerperal infection; however, combination therapy of anti-TNFs and thiopurines was associated with increased risk of preterm births (6.75% vs 19.15%; p=0.001) and risk for severe acute respiratory infections in the first 2 years of life.

All the immunosuppressant drugs were associated with increased risk for severe acute respiratory infection in the first 2 years of life, more significantly in combination therapy (p<0.001).

Importantly, the use of steroids in IBD showed a significant increased risk for preterm birth, IUGR and stillbirth (7.83% vs 13.74%, 2.5 vs 5.13% and 0.71% vs 1.83%; p=0.006, respectively). In the non-IBD population, steroid use was also associated with fetal abnormalities (1.77% vs 2.39%). These side effects were not seen with budesonide, probably because of the lower dosage per treatment and lower blood levels in comparison with prednisone of intravenous steroids.

It is possible that, in fact, the risk associated with steroids does not represent the side effects of the drug but rather a poor control disease during which the steroids are only masking the ongoing activity of the inflammation. In either case, corticosteroids do not represent a safe treatment option.

We conclude that the use of biologics and thiopurine in IBD pregnancy is not associated with a higher risk of complications when compared with the general population, unless when used in combination with steroids. Corticosteroids may be useful in an acute setting to control the flare-ups, but long-term use in pregnancy is associated with poor outcomes for the mother and the baby.

Read Abstract

Author Contact

Brindusa Truta Johns Hopkins University School of Medicine, Department of Medicine

Media Interview Requests:

To arrange an interview with any ACG experts or abstract authors please contact Jacqueline Gaulin of ACG via email or by phone at 301-263-9000.