Rheumatoid Arthritis Treatments - TNF Inhibitors
Anti-TNF Therapy and Pregnancy Outcomes
FRI0107 Pregnancy in Women Receiving Anti-TNF-alpha Therapy. Experience in Spain
Garcia, Joven, Ruiz, Moreno et al.
and
FRI0119 Pregnancy Experience in Women with Rheumatic Diseases Exposed to Biologic Agents: Results from the BSR Biologics Register.
Hyrich, Watson, Dixon, Silman, et al
The safety of TNF inhibitors in pregnancy is not clear given the limited data available. Although, the numbers are small in each study, two abstracts, FRI0107 and FRI0119, describe pregnancy outcomes in women with rheumatic diseases exposed to anti-TNF agents at, or just prior to, conception.
FRI0107 Garcia et al reviewed records from the Spanish registry for adverse events of biological therapies in rheumatic diseases (BIOADASER). Of 3550 women taking TNF inhibitors, 14 pregnancies were identified in 13 women. Mean age at initiation of therapy was 28.9+4.9, after a mean disease duration of 11.7+7.1 years. Seven patients received biologic treatment for rheumatoid arthritis (RA), 4 for idiopathic juvenile arthritis (JIA) and 2 for psoriatic arthritis (PsA). Four pregnancies occurred during treatment with infliximab (IF) (exposure in the 1st month), 8 with etanercept (ET) (exposure in weeks 5-14) and 2 with adalimumab (AD) (exposure in week 4-6).
Results: Of the 14 pregnancies, 7 live births occurred without any complication (3 with IF, 4 with ET). Therapeutic terminations were performed in 3 cases (2 with ET, 1 with AD). One miscarriage (with IF) occurred and no outcome data were available for 2 patients. There were no fetal complications in three patients with maternal diabetes, one of whom was taking steroids. Endometriosis was reported during the first trimester of one pregnancy.
FRI0119 - This was a prospective study using the British Society for Rheumatology Biologics Register. Baseline questionnaires were issued at the start of anti-TNF therapy and every 6 months thereafter. As of 8/1/05, 8262 females were being treated, of which 35 pregnancies were reported. The outcome is known is 32 cases.
Results: The majority of patients had RA, mean age 31.5 years, and 11 years disease duration. A total of 35 pregnancies were reported; the outcome was known in 29 pregnancies. Of these, 23 were directly exposed to anti-TNF therapy at the time of conception (16 ETA, 3 INF, 3 ADA). Nine were also receiving methotrexate, and 1 leflunomide, at conception. All but 2 discontinued therapy in the first trimester following confirmation of pregnancy.*
| Pregnancy Outcomes in 23 patients who were directly exposed to anti-TNF therapy | |||
| Live Births (n=14) |
First Trimester Miscarriages (n=6) |
Elective Termination (n=3) |
|
| Anti-TNF agents: | Etanercept (n=10) Infliximab (n=2) Adalimumab (n=2) |
Etanercept (n=4) Infliximab (n=1) Adalimumab (n=1) |
Etanercept (n=3) |
| Concurrent DMARDs: | Methotrexate (n=4) Leflunomide (n=2) |
Methotrexate (n=3) | Methotrexate (n=2) |
| *1. The mother remained on Etanercept to week 20. An emergency c-section at term was done due to fetal distress, however, mother and infant were well. 2. Mother remained on etanercept throughout the pregnancy. Delivery was by c-section with a postpartum hemorrhage, but mother and infant did well. | |||
| Pregnancy Outcomes in 9 patients who discontinued anti-TNF therapy prior to conception: | ||
| Live Births (n=8) |
Miscarriages (n=1) |
|
| Anti-TNF agents: | Etanercept (n=3) Infliximab (n=6) |
Etanercept (n=1) |
Therapy was discontinued a mean of 5 months (1-10) prior to conception. Methotrexate use 4-6 months prior to conception occurred in 3 patients and methotrexate plus sulfasalazine in 1 patient. Complications were reported in 2 cases, both with etanercept and methotrexate use 4 months pre-conception: intrauterine death of one fetus in a twin pregnancy (other twin well) and 1 pre-eclampsia.
No congenital malformations were reported in either direct or prior exposure pregnancies. Additionally, the overall first trimester miscarriage rate is ~30% in the UK.
Editorial Comment: These data are reassuring but much larger numbers will be needed for any definitive conclusions about the safety of anti-TNF therapy during pregnancy. Also, it is important to keep in mind that most of these patients did not receive anti-TNF therapy throughout their pregnancies. Most of the patients were exposed only for a few weeks until conception was recognized.