Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
First Experiences with Pregnancies in RA Patients (pts) Receiving Tocilizumab (TCZ) Therapy.
Rubbert-Roth4, Andrea, Goupille1, Philippe M., Moosavi3, Shahrzad, Hou2, Antony
TCZ, an IL-6 receptor inhibitor, reduces signs and symptoms of RA and inhibits joint damage progression in RA pts. Women of childbearing potential were required to use a reliable contraception method in TCZ clinical trials. However, pregnancies did occur during TCZ use in clinical studies. TCZ has an FDA label of pregnancy category C (no adequate and well-controlled studies in humans; should be used in pregnant women only if potential benefit justifies potential risk to fetus). The purpose of this analysis was to describe pregnancies and their outcomes in RA pts receiving TCZ in clinical studies.
The analysis included all pregnancies reported in RA pts who received TCZ in one phase 1 study, five phase 3 trials (OPTION, TOWARD, RADIATE, AMBITION, LITHE), and 2 ongoing open-label extension studies (GROWTH95/96). Pts received 1 dose of TCZ 10 mg/kg in the phase 1 study, TCZ 4 or 8 mg/kg Q4W in phase 3 trials, and TCZ 8 mg/kg Q4W in extensions. Cutoff date was August 28, 2009.
A total of 4009 pts (10,994 pt-years) were included. Thirty-three pregnancies were reported in 32 pts, despite a requirement for contraceptive use. All pts had received TCZ 8 mg/kg, except 1 pt who received TCZ 4 mg/kg. Of 32 pts, 26 received TCZ + MTX and 6 received TCZ monotherapy or a concomitant DMARD other than MTX. Most of the 32 pts conceived while using a condom as a primary or secondary contraception method followed by hormonal contraceptive. Some pts used more than one method. Two patients did not use any contraceptive method. Pt age at conception was 19 to 42 y; 10 were >=35 y. In pts who continued their pregnancies, TCZ and MTX were stopped when the pregnancy was known. Thirteen of 33 pregnancies were therapeutically aborted, 7 (3 pts were >=35 y) spontaneously aborted, and 11 resulted in term delivery. Outcome was unknown for 2 pregnancies (1 lost to follow-up; 1 outcome not confirmed). Of 7 spontaneous abortions, all occurred within ~2 months of conception; all pts received TCZ 8 mg/kg, and 5 received concomitant MTX at conception. Of 11 term deliveries, 10 were of healthy newborns (1 infant died of ARDS 3 days after emergency cesarean section for intrapartum fetomaternal hemorrhage due to placenta previa). All mothers who delivered to term had received TCZ 8 mg/kg; 9 had received concomitant MTX, and 2 had received TCZ monotherapy.
The amount of clinical trial data about pregnancy outcomes in women exposed to TCZ during pregnancy is limited. The low number of cases and the high rate of therapeutic abortions, as well as concomitant medication use, limit the conclusions that can be drawn regarding the safety of TCZ during pregnancy. Physicians should be aware of the pregnancy information in local prescribing information and advise women of childbearing potential to use reliable methods of contraception before initiating treatment with TCZ. Hormonal contraceptives are substrates of CYP450, and the effect of TCZ on the reliability of hormonal contraceptives is being assessed in a separate clinical trial. A pregnancy registry is being established to assess pregnancy outcomes in women exposed to TCZ during pregnancy.
To cite this abstract, please use the following information:
Rubbert-Roth, Andrea, Goupille, Philippe M., Moosavi, Shahrzad, Hou, Antony; First Experiences with Pregnancies in RA Patients (pts) Receiving Tocilizumab (TCZ) Therapy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :384