Sustained Humoral and Cell-Mediated Immunogenicity of COVID-19 Vaccines in Patients With Inflammatory Bowel Disease

Study Overview
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Brief Summary
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The aim of this study is to determine the impact of systemic immunosuppression on sustained antibody COVID-19 concentrations in patients with IBD who received a COVID-19 vaccine.

Official Title
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Sustained Humoral and Cell-Mediated Immunogenicity of COVID-19 Vaccines in Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Biological: COVID-19 Vaccine


Participation Criteria
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Eligibility Criteria
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A patient will be eligible for inclusion in this study if he or she meets all the following criteria: Patient is between the ages of 18-85 years, inclusive Patient has a history of ulcerative colitis (UC), or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria On one of the following treatment regimens for at least three months at the time of immunization and continued same therapy at the time of recruitment. Should be on stable doses defined as: Group A should have taken a dose of medication within the past week; Group B infliximab within the previous 8 weeks, golimumab within the previous 4 weeks, adalimumab within the previous 2 weeks, or certolizumab within the previous 4 weeks; Those on combination therapy in group B will have taken azathioprine or methotrexate within the past week. Group C ustekinumab at least within the previous 4 weeks. Those on combination therapy in group C will have taken azathioprine or methotrexate within the past week; Group D vedolizumab at least within the previous 4 weeks. Those on combination therapy in group D will have taken azathioprine or methotrexate within the past week Group A non-biologic group: mesalamine monotherapy or thiopurine monotherapy Group B: Anti-TNF Therapy Group: on maintenance therapy infliximab (at least 5mg/kg every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly Combination Therapy Anti- TNF Combination Therapy Group: on anti-TNF therapy as described above along with either 15mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg at least 40% of the group; Approximately 40-50% of the group will be combination therapy Group C: Ustekinumab on either ustekinumab monotherapy or combination therapy with methotrexate or azathioprine Group D: Vedolizumab Therapy Group: Vedolizumab Therapy: on either vedolizumab monotherapy or combination therapy with methotrexate or azathioprine Patient received at least two doses of mRNA COVID-19 vaccine per standard of care A patient will not be eligible for inclusion in this study if he or she meets all the following criteria: Patient cannot or will not provide written informed consent Unable to provide appropriate informed consent due to being illiterate or impairment in decision-making capacity Received a COVID-19 booster within the previous 28 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A Non-biologic Group<br>Participants on treatment regimen of mesalamine monotherapy or thiopurine monotherapy, or corticosteroids. | Biological: COVID-19 Vaccine<br>* Three-dose mRNA COVID-19 vaccine per standard of care<br>|
| Group B Anti-TNF Group<br>Participants on treatment regimen of maintenance montherapy of infliximab (at least 8 every 8 weeks), golilumamb (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly), or combination therapy of anti-TNF therapy as described above along with either 15mg of methotrexate or azathiprine at least 1.0mg/kg or 6MP 0.5mg/kg. | Biological: COVID-19 Vaccine<br>* Three-dose mRNA COVID-19 vaccine per standard of care<br>|
| Group C Ustekinumab Group<br>Participants on treatment regimen of ustekinumab monotherapy or combination therapy with methotrexate or azathioprine. | Biological: COVID-19 Vaccine<br>* Three-dose mRNA COVID-19 vaccine per standard of care<br>|
| Group D Vedolizumab Group<br>Participants on vedolizumab monotherapy or combination therapy with methotrexate or azathioprine. | Biological: COVID-19 Vaccine<br>* Three-dose mRNA COVID-19 vaccine per standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the immunogenicity of the COVID-19 vaccines by measuring geometric mean titers (GMT) of SARS-CoV-2 antibody concentrations, and quantitative assays to evaluate RBD-binding IgG levels | Evaluation of the immunogenicity of the COVID-19 vaccines prior to patients receiving a COVID-19 booster during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster. Quantitative assays will be used to evaluate RBD-binding IgG levels. | 6 and 12 months after third dose of the COVID-19 vaccine, with primary outcome being sustained antibody concentrations at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained cell-mediated immunity against Covid-spike proteins will be evaluated using IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors. | Evaluation of sustained cell mediated immunity against Covid-spike proteins. IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors, will be used to detect T-cell immunity to the Covid-spike protein or peptides. | during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster | 
| Evaluate the persistence of memory B cell using memory B cell analysis. | Evaluation of the persistence of memory B cell in approximately one-third of participants. | during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster | 
| Sustained antibody concentration evaluating spike protein and receptor binding | The NIH ELISA assay will be used to evaluate change in S and RBD (IgG and IgM) antibody titers. | during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster |