Vaccine Response to COVID-19 Vaccines in Patients Using Immunosuppressive Medication

Study Overview
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Brief Summary
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The purpose of this study is to assess the strength and duration of the immunological response to COVID-19 vaccines in patients treated with immunosuppressive and/or immunomodulating medication for immune-mediated inflammatory diseases in rheumatology and gastroenterology and after a liver transplantation.

Detailed Description
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Patients on long-term immunosuppressive and/or immunomodulating medication may be susceptible to serious COVID-19. Hence, it is important they get sufficient protection by a COVID-19 vaccine. However, these patients may also be at risk for a less robust vaccine response. There is an urgent need to assess the humoral and cellular immune response to COVID-19 vaccines in these patient groups. The clinical consequences could be to administer several re-vaccinations or to adjust medication. This prospective, observational study aims to assess the immune response after COVID vaccination in patients suffering from inflammatory diseases and using immunosuppressive medication. Also, liver transplanted patients on immunosuppressive medication will be included. Serum and whole blood samples will be obtained from all participants before and 1-4 weeks after the vaccination. Additionally, serum samples will be collected every 3-6 months for 5 years. If patients are allotted further vaccine doses , the patient response will be assessed by blood tests 2-4 weeks after any additional vaccine doses. In a subset of patients, samples will be drawn to study cellular immune responses. Demographic data and data regarding immunosuppressive medication will be recorded. Disease activity (clinical activity indices and biomarkers of inflammation) will be assessed. Blood samples will be obtained for biobank. Information regarding vaccination status and potential COVID-19 testing will be obtained from relevant registers.

Official Title
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A Norwegian Study of Vaccine Response to COVID-19 Vaccines in Patients Using Immunosuppressive Medication Within Rheumatology and Gastroenterology: the Nor-vaC Study

Conditions
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Rheumatoid Arthritis, Psoriatic Arthritis, Spondyloarthritis, Crohn Disease, Ulcerative Colitis, Autoimmune Hepatitis, Liver Transplant; Complications

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An established clinical diagnosis of one of the following immune-mediated diseases: rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), ulcerative colitis (UC,) Crohns disease (CD), autoimmune hepatitis (AIH) or patients who have undergone a liver transplantation Treatment with relevant immunosuppressive and/or immunomodulating medication * Adult patients (> 18 years) Patient intends to obtain vaccination against COVID-19 during the next 6 months * The following drugs are considered relevant immunosuppressants and/or immunomodulators and patients using them may be eligible for this study: Rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept, tocilizumab, abatacept, secukinumab, vedolizumab, ustekinumab, risankizumab, methotrexate, sulfasalazine, leflunomide, azathioprine, 6-mercaptopurine, tofacitinib, filgotinib, baricitinib, upadacitinib, tacrolimus, mycophenolate, prednisolone Exclusion Criteria: 1) Allergy or intolerance to elements of the COVID-19 vaccines -

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Rheumatoid arthritis<br>Patients with a clinical diagnosis of rheumatoid arthritis and treated with immunosuppressive medication | |
| Psoriatic arthritis<br>Patients with a clinical diagnosis of psoriatic arthritis and treated with immunosuppressive medication | |
| Spondyloarthritis<br>Patients with a clinical diagnosis of spondyloarthritis and treated with immunosuppressive medication | |
| Crohn disease<br>Patients with a clinical diagnosis of Crohn disease and treated with immunosuppressive medication | |
| Ulcerative colitis<br>Patients with a clinical diagnosis of ulcerative colitis and treated with immunosuppressive medication | |
| Autoimmune hepatitis<br>Patients with a diagnosis of autoimmune hepatitis and treated with immunosuppressive medication | |
| Liver transplant<br>Patients who have undergone liver transplantation and are treated with immunosuppressive drugs | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serological response | Change from baseline in serum levels of anti-SARS-CoV-2 antibodies | 4 weeks after vaccination, then at 3 month intervals during the first year and 6 month intervals for up to a total of 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cellular response | Change from baseline in T cell reactivity to SARS-CoV-2 | 7-10 days after vaccination, then at 3 month intervals during the first year and 6 month intervals for up to a total of 5 years | 
| Adverse events | Occurence of patient-reported adverse events related to vaccination against COVID-19 | Reported by patient for the first 48 hours following each vaccine dose | 
| BASDAI | BASDAI questionnaire to assess disease activity in spondyloarthritis | Within 4 weeks of the patient receiving the final dose of vaccine | 
| Partial Mayo score | Partial Mayo score to assess disease activity in ulcerative colitis | Every 3 months for the first year of study, every 6 months thereafter until study completion | 
| Harvey-Bradshaw index (HBI) | Harvey-Bradshaw index to assess disease activity in Crohn disease | Every 3 months for the first year of study, every 6 months thereafter until study completion | 
| DAS28 | Disease Activity Score 28 to assess disease activity in RA and PsA | Within 4 weeks of the patient receiving the final dose of vaccine |