A review published in the International Journal of Molecular Sciences highlights existing knowledge gaps in understanding the safety and impact of tumor necrosis factor (TNF) α inhibitors in pregnant women suffering from inflammatory conditions such as psoriasis and rhaumatoid arthritis.
The ethical constraints that prevent inclusion of pregnant women in clinical trials results in a significant knowledge gap in the amount of information available to physicians, who then have to rely on postmarketing data and case studies to understand drug performance in this population. This is a particularly daunting task among pregnant women who suffer from psoriasis, due to limited knowledge on the safety of antiinflammatory agents—tumor necrosis factor (TNF) α inhibitors—in treating these patients.
In a review published in the International Journal of Molecular Sciences, researchers from Denmark evaluate the current landscape of treatments available for pregnant women suffering from inflammatory conditions, and examine guidelines that exist, if any.
Hormonal changes experienced during pregnancy fluctuate the degree of psoriasis and also influence comorbidities including obesity, hypertension, diabetes, and other chronic inflammatory conditions such as rheumatoid arthritis (RA), all of which can have a negative impact on the fetus, the authors write. Disease pathophysiology points to an imbalance in the immune system—specifically, increase in Th17 cells—can disrupt the Th17/regulatory T cell ratio and may impact the status of the pregnancy, and eventually, the outcome.
With the risk that TNFα inhibitors may cross the placental barrier, guidelines developed by the British Association of Dermatologists recommend a case-by-case determination of treating pregnant women with psoriasis or psoriatic arthritis with adalimumab, golimumab, etanercept, or certolizumab pegol, the indicated TNFα inhibitors. According to the European Crohn’s and Colitis Organization, women with inflammatory bowel disease (IBD) should be treated appropriately, to avoid risks to the mother or the fetus, but treatment should be discontinued if possible between gestational weeks 24 and 26.
Below are some of the safety considerations listed in the review:
In their conclusion, the authors point to the wide knowledge gap, particularly around the safety of TNFα inhibitors in pregnancy, and long-term outcomes in children exposed to these agents. Additionally, they also point to the quality of evidence and indicate the need to reduce heterogeneity between studies, curb extrapolation of results (eg, conduct specific studies for psoriasis), narrow confidence intervals for adverse outcomes, and power the trials.
Johansen CB, Jimenez-Solem E, Haerskjold A, Sand FL, Thomsen SF. The use and safety of TNF inhibitors during pregnancy in women with psoriasis: a review. Int J Mol Sci. 2018;19(5). pii: E1349. doi: 10.3390/ijms19051349.