Are anti–TNF-alpha agents safe in pregnant women with rheumatoid arthritis (RA)?

Updated: May 11, 2018
  • Author: Katherine K Temprano, MD; Chief Editor: Christine Isaacs, MD  more...
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Medications in the anti–tumor necrosis factor (TNF)-alpha class (eg, etanercept, adalimumab, infliximab, golimumab, and certolizumab) are commonly used in the treatment of RA. These agents have been labeled as class B medications; animal studies have shown no harm to the fetus, [34, 35] but thus far, no randomized, blinded, placebo-controlled trials on potential teratogenicity in humans have been completed. Numerous case reports have shown positive outcomes with anti–TNF-alpha use in pregnancy, with an incidence of spontaneous abortion and birth defects similar to that in the general population. [4, 6, 7, 8, 36, 37, 38, 39]

Pregnancy outcomes of 495 women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational multicenter cohort study and compared with 1532 outcomes from a non-exposed random sample. Major birth defects were reported in 5% of the exposed group as compared to 1.5% in nondiseased controls. The risk of preterm birth was increased, but not the risk of spontaneous abortion. Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). [40]

A meta-analysis of 13 studies evaluating the risk of pregnancy outcomes in patients with various immune-mediated diseases (including RA, IBD, and others) treated with anti–TNF-α agents found that anti-TNF treated patients were at risk for preterm birth, spontaneous abortion and low birth weight compared with the general population, but the risks were comparable to those in female patients with immune-mediated diseases who were not treated with anti–TNF-α agents. [41]

The death of a 4.5-month-old infant from disseminated tuberculosis following routine bacillus Calmette-Guerin (BCG) vaccination at 3 months of age has been linked to the mother’s treatment with infliximab during pregnancy. It has been suggested that clinicians exercise caution in the use of anti-TNF in late pregnancy and that neonates who have had exposure to anti-TNF agents in utero should not receive any live vaccines for the first 6 months of life. [42]

The individual TNF inhibitors differ in terms of placental transfer. Certolizumab may have a safety advantage, as smaller amounts of the drug are known to pass into fetal circulation. [29]

A comparison of pregnancy outcomes of 74 women exposed to adalimumab and 80 women with RA not exposed found no difference in the frequency or relative risk of major birth defects between adalimumab-exposed women, unexposed women with RA, and healthy women. Among the specific birth defects in the adalimumab cohort, no pattern was evident. Preterm delivery occurred at similar rates in the adalimumab-exposed and RA comparison groups (adjusted hazard ratio [HR]=1.08, 95% CI 0.41 to 2.83). [43]

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