ACR: Don’t stop TNFis during rheumatoid arthritis pregnancy

SAN FRANCISCO – It might be best to keep women with rheumatoid arthritis on their tumor necrosis factor blockers during pregnancy, according to German investigators.

They found that women are likely to flare without them and need more prednisolone, which is associated with preterm birth and other problems, while an increasing body of evidence suggests that tumor necrosis factor inhibitors (TNFis) are relatively safe during pregnancy.

“We should” rethink discontinuing TNFis during pregnancy, as recommended in some quarters. “We do not want women to flare during pregnancy,” said investigator Dr. Rebecca Fischer-Betz of the department of rheumatology at Heinrich Heine University in Düsseldorf.

Dr. Rebecca Fischer-Betz

She and her colleagues compared birth outcomes in 18 rheumatoid arthritis (RA) patients who discontinued TNFi treatment shortly after they got pregnant against those of 24 women with RA who were never exposed to a TNFi because, in general, they had less severe disease.

Twelve of the women (75%) in the TNFi group flared, versus four women (17%) in the control group. Although patients in both groups started with a mean 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) below 3.0, women in the TNFi group had a rise in activity to a mean of about 3.5 in the second trimester, while disease activity in control patients remained stable.

Compared with controls, women who stopped TNFis were also far more likely to flare (odds ratio, 10.0; 95% confidence interval, 2.3-42.8; P = .002), even after adjusting for age, DAS28-CRP at conception, rheumatoid factor and cyclic citrullinated peptide status, and other potential confounders. They also relied more heavily on prednisolone, taking, for example, a mean dose of 13 mg in the second trimester versus 8 mg in the control group. Perhaps not surprisingly, the mean duration of pregnancy was 37 weeks in the TNFi group, with six women (33%) delivering at or before 37 weeks; women in the control group delivered, on average, at 39 weeks, with four (17%) delivering at or before week 37.

The investigators found that the risk of preterm birth increased with every cumulative milligram of prednisolone (OR, 1.08; 95% CI, 1.02-1.15; P less than .01).

“Women with RA who discontinue TNFis at conception face a high risk for flares during pregnancy, independently of known risk factors like seropositivity. Flares are usually treated with prednisolone. We found a dose-dependent, significant increased risk for preterm birth associated with prednisolone. In this era of treat-to-target management of RA, our paradigm for RA pregnancy management may need adjusting. By controlling RA activity with medications considered relatively safe in pregnancy, we may be able to improve both the pregnancy experience and pregnancy outcomes,” the investigators concluded.

The women were 33 years old on average, and all had live births; four early miscarriages were excluded from analysis. All the pregnancies were planned, with methotrexate discontinued at least 3 months before conception. There was no statistical difference in the rate of seropositivity between the groups, “which is interesting because we know seropositivity is a risk factor for staying active during pregnancy,” Dr. Fischer-Betz said.

Two boys born to women who took TNFis had minor malformations, one with nasal bone aplasia, retrognathia, and hydronephrosis, and the other with hypospadias. Both of their mothers had taken etanercept (Enbrel) in the first trimester. There was one malformation in the control group, a girl born with hydronephrosis.

There was no outside funding for the work, and the investigators have no disclosures.

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