Serological responses to vaccination in children exposed in utero to ustekinumab or vedolizumab: cross-sectional analysis of a prospective multicentre cohort.

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.

Tofacitinib in Pregnancy: Assessing Pregnancy and Infant Outcomes, Cord Blood, and Breast Milk Concentrations.

Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.

Subcutaneous Infliximab in Refractory Crohn's Disease Patients: A Possible Biobetter?

Background: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. Methods: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. Results: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 µg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. Conclusions: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.

Patient-reported symptoms are a more reliable predictor of the societal burden compared to established physician-reported activity indices in inflammatory bowel disease: a cross-sectional study.

BACKGROUND: The societal burden of inflammatory bowel diseases (IBD) is not well documented, and further studies are needed to quantify the costs of the disease state. Thus, the aim was to estimate the societal burden and identify its predictors. METHODS: A cross-sectional questionnaire-based study complemented by objective data from patient medical records was performed for patients with Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: We analyzed data from 161 patients (CD: 102, UC: 59). The overall work impairment reached 15.4%, 11.2% vs. 28.8% without/with self-reported symptoms (p = 0.006). Daily activity impairment was 19.3%, 14.1% vs. 35.6% (p < 0.001). The disability pension rate was 28%, 23% vs. 44% (p = 0.012). The total productivity loss due to absenteeism, presenteeism, and disability amounted to 7,673 €/patient/year, 6,018 vs. 12,354 €/patient/year (p = 0.000). Out-of-pocket costs amounted to 562 €/patient/year, 472 vs. 844 €/patient/year (p = 0.001). Self-reported symptoms were the strongest predictor of costs (p < 0.001). CONCLUSION: We found a high societal burden for IBD and a significant association between patient-reported disease symptoms and work disability, daily activity impairment, disability pensions, and out-of-pocket costs. Physician-reported disease activity is not a reliable predictor of costs except for out-of-pocket expenses.

Cellular and Humoral Immune Responses to SARS-CoV-2 Vaccination in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Knowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease [IBD] patients is limited. Therefore, SARS-CoV-2-specific T-cell responses and antibodies were analysed in 60 IBD vaccine recipients and 30 controls. METHODS: SARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. A SARS-CoV-2 interferon-gamma released assay [IGRA] was performed in all vaccinees at week 26. RESULTS: At weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 [18%] vaccinated individuals had a negative IGRA test result, seven of 90 [8%] were borderline and 67 [74%] had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However, the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinated individuals with low or borderline IGRA, treatment with tumour necrosis factor-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient. CONCLUSIONS: Simple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled.

Anti-SARS-CoV-2 Vaccination and Antibody Response in Patients With Inflammatory Bowel Disease on Immune-modifying Therapy: Prospective Single-Tertiary Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.