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AB1096 Exposure of Drugs for Autoimmune Disease during Pregnancy and Perinatal Outcomes: an Investigation of the Regulator in Japan
  1. R. Sato1,
  2. M. Ikuma1,
  3. K. Takagi1,
  4. J. Asano1,
  5. Y. Yamagishi1,
  6. Y. Matsunaga1,
  7. H. Watanabe2
  1. 1Pharmaceuticals and Medical Devices Agency, Tokyo
  2. 2Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan


Background In certain circumstances, drugs for autoimmune disease are continued to be prescribed to pregnant women. Especially, various kinds of biological agents for autoimmune disease are being brought to the market in recent years and the safety of these drugs in perinatal periods is still uncertain.

Objectives To investigate descriptive data of adverse drug events in perinatal periods which were reported to the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and evaluate impacts of the exposure of drugs for autoimmune disease on perinatal outcomes.

Methods We reviewed the PMDA regulatory databases for adverse drug events in perinatal periods which were reported between January 2012 and October 2013. Autoimmune disease in the present study was defined according to the ICD-10 codes. Drugs for autoimmune disease were categorized into steroids, biological agents (monoclonal antibody and Fc fusion protein), other immunosuppressants, NSAIDs and anti-thyroid drugs (methimazole and propylthiouracil), as to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification. Main outcome measures were fetal death (miscarriage, stillbirth and abortion due to medical reasons) and neonatal death. Logistic regression analysis, which included maternal age and BMI, was performed to estimate adjusted odds ratios (ORs) for perinatal outcomes by clinical factors including drug exposure during pregnancy were estimated.

Results We identified 521 cases (maternal age: 15-47 yrs; mean 32.3±5.5), of which 130 were miscarriage, 12 stillbirth and 4 neonatal death. Mean values of birth weight and gestational age of the infants were 2441±782 g and 35.7±4.0 wk, respectively. Malformation was reported in 122 cases; 35, very low birth weight (<1500 g); 45, small for gestational age; 43, Apgar score at 5 min <7. Of the 521 cases, 123 had autoimmune disease (11, rheumatoid arthritis; 11, SLE; 80, autoimmune thyroid disease; 4, inflammatory bowel disease). Sixty-six cases received steroids; 15, biological agents; 36, other immunosuppressants; 21, NSAIDs; 75, anti-thyroid drugs. Advanced maternal age (35≤) was associated with an increase in fetal/neonatal death (adjusted OR 2.24, 95% CI 1.32-3.80, P<0.01). Steroids, biological agents, other immunosuppressants, NSAIDs and anti-thyroid drugs were not associated with fetal/neonatal death. Malformation of infants was less frequent in the steroids exposure group (adjusted OR 0.21, 95% CI 0.07-0.61, P<0.01). On the other hand, anti-thyroid drugs were related to malformation (adjusted OR 23.3, 95% CI 10.9-49.8, P<0.01), but not to multiple malformation (two or more types of malformation). Biological agents were associated with multiple malformation (adjusted OR 8.50, 95% CI 1.40-51.1, P=0.02). Steroids and other immunosuppressants were both associated with low birth weight (<2500g). Very low birth weight tended to be frequent in the NSAIDs exposure group (adjusted OR 4.72, 95% CI 0.99-22.5, P=0.05).

Conclusions Advanced maternal age was associated with fetal/neonatal death. None of the drug categories for autoimmune disease in the study was detected as a related factor for fetal/neonatal death. Effects of biological agents exposure on multiple malformation may be unfavorable and further investigation is warranted.

Disclosure of Interest R. Sato: None declared, M. Ikuma: None declared, K. Takagi: None declared, J. Asano: None declared, Y. Yamagishi: None declared, Y. Matsunaga: None declared, H. Watanabe Grant/research support: the Ministry of Health, Labour and Welfare of Japan, Teika Seiyaku, Takeda Pharmaceuticals, Mochida, Pfizer, Asteras and Daiichi Sankyo, Consultant for: Pfizer, Acterion, Novartis, Daiich Sankyo, GlaxoSmithKline and Nihon Shinyaku

DOI 10.1136/annrheumdis-2014-eular.4118

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