Corinna Weber-Schoendorfer1, Marc Oppermann1, Evelin Wacker1, Nathalie Bernard2, Delphine Beghin3, Benedikte Cuppers-Maarschalkerweerd4, Jonathan L Richardson5, Laura E Rothuizen6, Alessandra Pistelli7, Heli Malm8, Georgios Eleftheriou9, Debra Kennedy10, Mine Kadioglu Duman11, Reinhard Meister12, Christof Schaefer1. 1. Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin, Berlin, Germany. 2. Centre Régional de Pharmacovigilance, Hospices Civils de Lyon, Lyon, France. 3. Centre de Référence sur les Agents Tératogènes (CRAT), Hôpitaux Universitaires Est Parisien (APHP), Paris, France. 4. Teratology Information Service, MH 's-Hertogenbosch, Netherlands. 5. UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University, Newcastle upon Tyne, United Kingdom. 6. Swiss Teratogen Information Service (STIS) and Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland. 7. Centro di Riferimento Regionale di Tossicologia Perinatale, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy. 8. Teratology Information Service, HUSLAB and Helsinki University Central Hospital, Helsinki, Finland. 9. Poison Control Centre and Teratology Information Service, Hospital Papa Giovanni XXIII, Bergamo, Italy. 10. Mothersafe, Royal Hospital for Women, Randwick, Australia. 11. Department of Pharmacology, Karadeniz Technical University, Trabzon, Turkey. 12. Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences), Berlin, Germany.
Abstract
AIMS: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. METHODS: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. RESULTS: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. CONCLUSIONS: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.
AIMS: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. METHODS: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. RESULTS: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. CONCLUSIONS: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.
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