Background Biological agents (“biologics”), such as anti-tumor necrosis factor (TNF) agents and interleukin-6 (IL-6) inhibitors, have been widely used in recent years for the treatment of rheumatoid arthritis (RA) to achieve remission.
A concomitant treatment of methotrexate (MTX) with biologics is recommended for RA patients refractory to MTX, particularly younger patients who need a high quality of daily life with less joint destruction and physical dysfunction.
Although RA is one of the systemic autoimmune diseases that can often occur in women of reproductive age, the evidence of successful treatment of patients who are pregnant or planning for pregnancy is limited due to a lack of prospective case-control studies.
Objectives Use of Tocilizumab (TCZ), such as interleukin-6 inhibitors, is recommended for patients who can not use the MTX.
A strategy that includes RA treatment, a safe pregnancy and a healthy fetus is clearly needed. Most cases of TCZ prescribed to pregnant RA patients were found to produce satisfactory outcomes, but further information on the association between TCZ and pregnancy is lacking.
The aim of this retrospective study is to investigate the details of TCZ use in pregnant RA patients, from planning the pregnancy to actual delivery, and to examine the pregnancy outcomes of RA patients treated before or at conception with TCZ.
Methods In 1356 cases of RA patients registered in Nagoya medical center, patients using biologics were 532 cases. Of which, patients treated with TCZ were 111 examples.
7 pregnancies were identified and observed from the 111 patients treated with TCZ
Results 7 pregnancy of patients in the TCZ use six cases (one case of preterm low birth weight infants), abortion was 1 cases. They age were from 28 years to 42 years. Five cases was (washout period was from 2 months to 11 months) pregnant after Biologics free. One case was continued TCZ during pregnancy. Medical condition had worsened during pregnancy are three cases, there were four cases of what deterioration was observed after delivery.
Conclusions TCZ is a pregnancy risk category C drug, according to the US FDA. The category C risk summary states the following: “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks”. Japanese drug information states that TCZ should be administered to pregnant patients only if the benefits outweigh the risks; therefore, TCZ use in pregnant RA patients is not necessarily prohibited. Still, some review papers have concluded that TCZ should be discontinued three months before conception reported that IL-6 was the one of the causes of preterm premature rupture of membranes (PPROM) and that TCZ inhibited IL-6-mediated matrix metalloproteinase-2 and -9 secretion from human amnion cells. Although their study showed that TCZ might be useful for treating PPROM, the data on TCZ and pregnancy in humans were too limited to make conclusions on safety or suggestions on prescriptions.
Østensen M, et al.Treatment with biologics of pregnant patients with rheumatic diseases. Curr Opin Rheumatol. 2011; 23: 293-8.
Disclosure of Interest None declared