Updated Tofacitinib Pregnancy Outcomes

The most recent pregnancy data for tofacitinib (abstract 1908) was reviewed at ACR 2014. Tofacitinib received a pregnancy category C in the US as a result of animal data where it was found to be both fetocidal and teratogenic at doses well above the maximum recommended human dose. No intervention studies have been conducted to examine the effects of tofacitinib in pregnant woman.

To date, there have been 35 reported pregnancies in women taking tofacitinib. The tofacitinib RA interventional studies accounted for 32 of these patients with about 17,000 pt-years of exposure. There were an additional 2 pregnancies reported in non-interventional post-approval safety studies and 1 spontaneous report.

The limitations of this analysis include the fact that it was not prospective and there was limited information about the date of conception and the gestational age.

Focusing on the 32 cases in the RA interventional studies, 31 received tofacitinib and the other received placebo methotrexate. Patient age ranged from 22-40, the total time on the study medication was 14-1404 days, and in the majority of cases there was less than 30 days in utero exposure.

Of the 31 cases the following outcomes occurred:

Healthy newborns: 16 (11 TOFA monotherapy & 5 combination therapy with MTX).
Spontaneous abortions: 6 (2 TOFA monotherapy & 4 combination therapy with MTX)
Medical termination: 4 (1 TOFA monotherapy & 3 combination therapy with MTX)
Still Birth: 1
On-going pregnancy: 1
Lost to follow-up: 3

Further examining the healthy newborns (16):

Dose of TOFA: 5 mg BID = 8, 10 mg BID = 8
Low birthweight: 2 (4.7 & 5.3 lbs)
Fetal complications: 1 – pulmonary valve stenosis

Further examining the spontaneous abortions:

The spontaneous abortion rate was 20.6%
Most cases of spontaneous abortion occurred in patients on concomitant MTX
Published estimates from RA cohorts quote a rate of spontaneous abortion of 22.5%

Based on this data, the safety of tofacitinib in pregnancy cannot yet be determined.

More reports from ACR 2014