Immunosuppressive Agents Increase Infection Risk in Pregnant Women With Inflammatory Conditions

Autoimmune disease develops when your immune system attacks healthy cells in your body. However, the exact cause of this disease is unknown. It is estimated that in the US more than 4.5 million patients are affected by autoimmune disorders, which includes diseases such as rheumatoid arthritis systemic lupus erythematosus (SLE), tumor necrosis factor α (TNF), celiac disease, scleroderma, and pernicious anemia, amongst others.

Research reveals that nearly 75% of those affected with autoimmune disorders are women and that flare-up are commonly seen during pregnancy. Control of disease activity is essential during pregnancy to avoid potential complications including preterm birth, intrauterine growth restriction and spontaneous abortions.

There is only limited information available on the safety of immunosuppressive drugs in pregnancy and many are contraindicated for use during pregnancy due to their teratogenic potential. Hence it is important to understand the risk of infections in pregnant women using immunosuppressive agents to be able to guide them appropriately in treatment selection.

Study

Research teams from Brigham and Women's Hospital at Harvard University in Boston conducted an observational cohort study to compare the risk of serious infections in pregnant women taking steroids, non-biologic immunosuppressive agents, or tumor necrosis factor α (TNF) inhibitors to treat various autoimmune conditions.

Data obtained from two large US health insurance databases, Medicaid and Optum Clinformatics were studied. Participants included 4961 pregnant women with a mean age of 29 years and were treated with immunosuppressive drugs for rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.

Patients were classified into steroid, non-biologic, or TNF inhibitors based on first filled prescription of these immunosuppressive agents during pregnancy. The date when the immunosuppressive prescription was filled for the first time during pregnancy was defined as the index date. Since TNF inhibitors are not used to treat systemic lupus erythematosus, women with this condition were excluded from comparisons involving TNF inhibitors.

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Outcome of the Study

The objective of the study was to see if any serious infections occurred after the index date during pregnancy. Infections leading to hospitalization such as bacterial infection (meningitis, encephalitis, cellulitis, endocarditis, pneumonia, pyelonephritis, septic arthritis, osteomyelitis, and bacteremia) or opportunistic infections (tuberculosis, systemic candidiasis, cryptococcosis, aspergillosis) were considered serious in nature.

Hazard ratios between immunosuppressive treatment and risk of serious infections were derived using Cox proportional hazard regression models after adjustment for confounding with propensity score fine stratification.

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Dose-response analysis was conducted in women filling at least one steroid prescription using a logistic regression model.

Results

• The study results revealed that out of 4961 participants who were treated with immunosuppressive agents, 71 participants (0.2%) experienced serious infections.
• Amongst the 2598 steroid users, 1587 non-biologic users and 776 TNF inhibitors users included in this study, the crude incidence rates of serious infections per 100 person years were reported to be 3.4 (95%), 2.3 (, and 1.5, respectively.
• In the adjusted primary analyses, no statistically significant differences were observed in the risk of serious infections during pregnancy amongst the three immunosuppressive drug classes:
• Non-biologics vs. steroids, hazard ratio 0.81 (95%)
• TNF inhibitors vs. steroids, hazard ratio 0.91
• TNF inhibitors vs. non-biologics, hazard ratio 1.36

• The dose-response analysis showed that high-dose steroid use was an independent risk factor for serious infections during pregnancy.
• The results also revealed that risk of serious infections was significantly higher in the later months of pregnancy in all three groups.

Strengths of the Study

• This is the first study of its kind to systematically analyze risk of serious infections in pregnant women undergoing treatment with immunosuppressive agents.
• The sample size used was large enough to be able to conduct additional stratified analysis by underlying inflammatory conditions as well as compare the results using meta-analytic methods.

Limitations of the Study

• The study only included women with a live-born infant and did not take into consideration use of some non-biologic agents which could result in abortions such as methotrexate, mycophenolate mofetil, amongst others.

Conclusion

• The results of this population-based cohort study revealed no significant difference in the risk of serious infections in pregnant women who used steroid monotherapy, non-biologics (monotherapy or in combination with steroids), and tumor necrosis factor α (TNF) inhibitors (monotherapy or in combination with steroids or non-biologics).
• On the other hand, steroid dose was found to be an independent risk factor for serious infections during pregnancy.

Reference:

1. Rishi J Desai, Brian T Bateman, Krista F Huybrechts, Elisabetta Patorno, Sonia Hernandez-Diaz, Yoonyoung Park, Sara Z Dejene, Jacqueline Cohen, Helen Mogun, Seoyoung C Kim. “Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study.” The British Medical Journal (2017); 356 doi: https://doi.org/10.1136/bmj.j895.

Source-Medindia