BACKGROUND: Reducing hospitalization length of stay (LOS) for acute severe ulcerative colitis (ASUC) will reduce healthcare costs, mitigate hospitalization-associated risks (e.g., venous thromboembolism), and improve quality of life. METHODS: A chart review was performed of all adult ASUC-related hospitalizations at University of California, San Francisco, from July 1, 2014, to December 31, 2017. Univariate and multivariate analyses were performed to identify factors associated with LOS < 7 days versus ≥ 7 days. A subgroup analysis was performed excluding patients who underwent colectomy during hospitalization. RESULTS: A total of 95 ASUC-related hospitalizations were identified. The initial univariable analysis identified the following factors associated with LOS ≥ 7 days (P < 0.05): higher maximum heart rate in the first 24 h, higher C-reactive protein, being biologic therapy naïve, and a later hospital day of biologic therapy initiation. On mixed model multivariable analysis, later hospital day of biologic initiation was associated with increased LOS ≥ 7 days (OR 3.1 95% CI 1.2-7.56, p = 0.012). CONCLUSIONS: We identified multiple predictors for longer hospital LOS, including factors related to disease severity (non-modifiable) and treatment (potentially modifiable). Importantly, this study identified biologic naïve treatment status and delayed inpatient biologic therapy initiation as predictors of longer LOS (≥ 7 days) in patients who did not ultimately require colectomy during their hospital stay. Potentially modifiable strategies to reduce LOS may include early communication and patient education about biologic therapy in both the inpatient and outpatient setting.

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Objectives

Infants 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.

Methods

We 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).

Results

Percentages of B cells, CD4⁺ T helper cells, T regulatory cells (T_regs), 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.

Conclusions

Multiparameter 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.

Background

Increasing evidence suggests that cytokine dysregulation in T-helper 1 and T-helper 2 (TH1/TH2) subsets contributes to the pathogenesis of Crohn disease (CD). The present pilot study examines the hypothesis that cytokine profiles differ between pediatric and adult patients with CD.

Methods

Production of TH1 cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and of TH2 cytokines interleukin-4 (IL-4) and IL-6 was analyzed in peripheral blood of patients with CD and healthy controls (n=20) using flow cytometry after in vitro stimulation.

Results

In both pediatric and adult subjects, frequencies of TNF-α CD4+ T cells were higher in patients with CD than in controls (P=0.009 and P=0.047, respectively). Percentages of cells expressing IL-4 were slightly increased (P=0.036), whereas those for IFN-γ were decreased (P=0.009) in pediatric patients with CD compared with controls. As expected, the overall production of TH1 cytokines was higher in adults compared with pediatric subjects. When memory CD4+CD45RO+ T cells were considered, lower IFN-γ expression was observed in pediatric subjects with CD compared with controls (P=0.009), matching the trend seen in the general CD4+ T cell population. The percentage of CD4+CD45RO+ T cells was increased in adult patients with CD compared with pediatric patients with CD (P=0.016).

Conclusions

The present study describes a peripheral blood TH1/TH2 cytokine imbalance in CD and suggests different immunological mechanisms in children and adults for disease pathogenesis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition that requires close monitoring. Digital health virtual care platforms can enable self-monitoring and allow providers to remotely surveil patients and efficiently identify those with active disease. OBJECTIVES: The primary aim was to design and implement an IBD remote monitoring program, identify predictors of patient engagement, and determine who found the chat to be a valuable tool. METHODS: We developed the IBD Virtual Care Chat, an electronic health record (EHR)-integrated chat to monitor electronic patient reported outcomes (ePROs), medication changes, and disease activity, and subsequently report concerning findings to providers via the EHR. All patients in the IBD practice over age 18 with a clinical encounter in the preceding 12 months were eligible to be enrolled. The primary aim was to identify predictors of patient engagement and determine who found the chat to be a valuable tool. RESULTS: Between May 2021 and March 2022, 2,934 patients were enrolled. A total of 1,160 engaged at least once and 687 (23.4%) continually engaged, submitting at least three ePROs. Disease severity (based on Harvey-Bradshaw Index or Simple Clinical Colitis Activity Index) did not impact ePRO submissions. Patients were significantly more likely to be continually engaged if they self-reported the presence of extraintestinal manifestations (7%, 95% confidence interval: 0.01-0.14; p = 0.04). Patient satisfaction remained moderately high with a median score of 8 (interquartile range: 5-10) on a scale of 1 (poor) to 10 (good). CONCLUSION: Our program demonstrates the potential for EHR-integrated digital health as part of routine IBD care to achieve sustained engagement with high patient satisfaction.

To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.

BACKGROUND AND OBJECTIVE: Upadacitinib is indicated for diseases affecting persons of childbearing potential including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, Crohns disease, and ulcerative colitis; however, teratogenicity was observed in animal studies. Given the potential for human fetal risk, pregnancy avoidance measures were required during clinical trials. This analysis describes pregnancy outcomes in patients exposed to upadacitinib during pregnancy. METHODS: Clinical trial and postmarketing cases of in utero exposure to upadacitinib were identified in AbbVies safety database through 25 April, 2023. Analysis of clinical trial cases and postmarketing reports are presented separately; prospective and retrospectively reported pregnancy outcomes are integrated for each. Descriptive rates are presented to summarize outcomes. RESULTS: There were 128 maternal upadacitinib-exposed pregnancies with known outcomes identified; 80 and 48 pregnancies were reported in clinical trials and the postmarketing setting, respectively. In clinical trials (mean in utero exposure of 5 weeks, 3 days), live births (54%), spontaneous abortions (24%), elective terminations (21%), and ectopic pregnancy (1%) were reported. There was one report of a congenital malformation: a 35-week infant with an atrial septal defect. In postmarketing cases, live births (46%), spontaneous abortions (38%), elective terminations (15%), and ectopic pregnancy (2%) were reported. CONCLUSIONS: As the data are limited for in utero exposure to upadacitinib, definitive conclusions cannot be drawn regarding the effect of upadacitinib on pregnancy outcomes. Rates of adverse pregnancy outcomes with upadacitinib exposure were comparable to rates observed in the general population or patients with autoimmune inflammatory diseases. To date, no apparent evidence of teratogenicity exists in the analyses of human pregnancies exposed to upadacitinib during the first trimester.

Background & aims

We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes.

Methods

Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607).

Results

As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads.

Conclusions

In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.