Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants

Abstract

ObjectivesInfants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system.MethodsWe immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD. We analyzed samples from infants exposed to infliximab (IFX) or adalimumab (ADA) monotherapy (IFX/ADA, n = 11), certolizumab pegol (CZP) monotherapy (CZP, n = 4), IFX or ADA plus thiopurine combination therapy (IFX/ADA + IM, n = 4), and CZP plus thiopurine combination therapy (CZP + IM, n = 2).ResultsPercentages of B cells, CD4+ T helper cells, T regulatory cells (Tregs), and CD8+ cytotoxic T cells, were similar among the groups. Infants exposed to combination therapy (IFX/ADA + IM) exhibited trends toward fewer CD27+ B cells, switched memory B cells, plasmablasts, interferon gamma (IFNγ)-producing CD4+ and CD8+ T cells, and CCR5+CD4+ T cells, but these did not reach statistical significance.ConclusionsMultiparameter immunophenotyping of major B-cell and T-cell subsets suggests that the adaptive newborn immune system develops largely unaltered after exposure to combination therapy as compared to anti-TNF monotherapy.

The Profile of Human Milk Metabolome, Cytokines, and Antibodies in Inflammatory Bowel Diseases Versus Healthy Mothers, and Potential Impact on the Newborn

“…Currently, a wide range of biological medications, immunosuppressants, and corticosteroid drugs are used to treat IBD and are considered low-risk throughout pregnancy and breastfeeding. [6][7][8][9] However, some of the medications used to manage IBD merit further investigations for their safety during preconception, pregnancy, and lactation. Due to the strong evidence that active IBD increases the likelihood of adverse pregnancy outcomes, therapeutic interventions during pregnancy are still considered as the primary option for protecting both mother and fetus.…”

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)—Part 1: Live Vaccines

“…68 Immunophenotyping studies have shown that anti-TNFexposed infants had more immature B-and helper T-cell phenotype at birth, 73 which normalized by 12 months. 73,77 A decreased response after mycobacterial challenge was noted in 1 study. 73 Observational studies have found that infants exposed to anti-TNF in utero have appropriate response to inactivated vaccines with no serious adverse events.…”

Immune function in newborns with in-utero exposure to anti-TNFα therapy

“…However, a decreased response after mycobacterial challenge at birth was noted, with no complete recovery after drug removal, suggesting that the immune system activation upon mycobacterial challenge may be compromised ( 9 ). Kattah et al ( 8 ), used multiparameter flow cytometry on 22 infants with different in utero exposures from the PIANO registry at age 12 months; (1 = no exposure, 4 certolizumab, 11 infliximab/adalimumab, 4 infliximab/adalimumab/immunomodulator, 4 certolizumab/immunomodulator). In those small different exposure groups, B and T lymphocyte subsets were preserved in all, with no increased risk of infections.…”