title: Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study.
abstract: ObjectiveTo compare the risk of serious infections associated with use of systemic steroids, non-biologic agents, or tumor necrosis factor α (TNF) inhibitors in pregnancy.DesignObservational cohort study.SettingPublic (Medicaid, 2001-10) or private (Optum Clinformatics, 2004-15) health insurance programs in the US.Participants4961 pregnant women treated with immunosuppressive drugs for rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.Exposure for observational studiesExposure was classified into steroid, non-biologic, or TNF inhibitors on first filled prescription during pregnancy. Because TNF inhibitors are not used to treat systemic lupus erythematosus, patients with this condition were excluded from comparisons involving TNF inhibitors.Main outcome measureThe main outcome was occurrence of serious infections during pregnancy, defined by hospital admission for bacterial or opportunistic infections. Hazard ratios were derived using Cox proportional hazard regression models after adjustment for confounding with propensity score fine stratification. A logistic regression model was used to conduct a dose-response analysis among women filling at least one steroid prescription.Results71 out of 4961 pregnant women (0.2%) treated with immunosuppressive agents experienced serious infections. The crude incidence rates of serious infections per 100 person years among 2598 steroid users, 1587 non-biologic users, and 776 TNF inhibitors users included in this study were 3.4 (95% confidence interval 2.5 to 4.7), 2.3 (1.5 to 3.5), and 1.5 (0.7 to 3.0), respectively. No statistically significant differences in the risk of serious infections during pregnancy were observed among users of the three immunosuppressive drug classes: non-biologicsvsteroids, hazard ratio 0.81 (95% confidence interval 0.48 to 1.37), TNF inhibitorsvsteroids 0.91 (0.36 to 2.26), and TNF inhibitorsvnon-biologics 1.36 (0.47 to 3.93). In the dose-response analysis, higher steroid dose was associated with an increased risk of serious infections during pregnancy (coefficient for each unit increase in average prednisone equivalent mg daily dose=0.019, P=0.02).ConclusionsRisk of serious infections is similar among pregnant women with systemic inflammatory conditions using steroids, non-biologics, and TNF inhibitors. However, high dose steroid use is an independent risk factor of serious infections in pregnancy.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA rdesai@bwh.harvard.edu.
authors.forename: Rishi J
authors.initials: RJ
authors.lastname: Desai
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.|Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Bateman
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
authors.forename: Krista F
authors.initials: KF
authors.lastname: Huybrechts
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Patorno
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernandez-Diaz
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Yoonyoung
authors.initials: Y
authors.lastname: Park
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
authors.forename: Sara Z
authors.initials: SZ
authors.lastname: Dejene
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Mogun
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
authors.forename: Seoyoung C
authors.initials: SC
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000453:epidemiology*; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology*; D012306:Risk; D014481:United States / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents