Clinical trial NCT04798625: Vaccine Response to COVID-19 Vaccines in Patients Using Immunosuppressive Medication
Official title: A Norwegian Study of Vaccine Response to COVID-19 Vaccines in Patients Using Immunosuppressive Medication Within Rheumatology and Gastroenterology: the Nor-vaC Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Rheumatoid Arthritis
Psoriatic Arthritis
Spondyloarthritis
Crohn Disease
Ulcerative Colitis
Autoimmune Hepatitis
Liver Transplant; Complications
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital, Akershus
First posted: 2021-03-15
Enrollment: 2300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Candidate patients will be recruited from the population treated at the two study centres and, if eligible, asked to participate in the observational cohort

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Treatment with relevant immunosuppressive and/or immunomodulating medication \*
3. Adult patients (\> 18 years)
4. 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

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Primary outcomes:
measure: Serological response
timeFrame: 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 outcomes:
measure: Cellular response
timeFrame: 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
measure: Adverse events
timeFrame: Reported by patient for the first 48 hours following each vaccine dose
measure: BASDAI
timeFrame: Within 4 weeks of the patient receiving the final dose of vaccine
measure: Partial Mayo score
timeFrame: Every 3 months for the first year of study, every 6 months thereafter until study completion
measure: Harvey-Bradshaw index (HBI)
timeFrame: Every 3 months for the first year of study, every 6 months thereafter until study completion
measure: DAS28
timeFrame: Within 4 weeks of the patient receiving the final dose of vaccine
Other outcomes:
Locations:
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Diakonhjemmet Hospital
Study officials:
References:
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citation: Syversen SW, Jyssum I, Tveter AT, Sexton J, Christensen IE, Tran TT, Bjorlykke KH, Mjaaland S, Warren DJ, Kvien TK, Chopra A, Kro GB, Jahnsen J, Munthe LA, Haavardsholm EA, Grodeland G, Vaage JT, Provan SA, Jorgensen KK, Goll GL. Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. RMD Open. 2022 Nov;8(2):e002417. doi: 10.1136/rmdopen-2022-002417.
citation: Bjorlykke KH, Orbo HS, Tveter AT, Jyssum I, Sexton J, Tran TT, Christensen IE, Kro GB, Kvien TK, Jahnsen J, Munthe LA, Chopra A, Warren DJ, Mjaaland S, Haavardsholm EA, Grodeland G, Provan SA, Vaage JT, Syversen SW, Goll GL, Jorgensen KK. Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. Lancet Rheumatol. 2023 Jan;5(1):e36-e46. doi: 10.1016/S2665-9913(22)00330-7. Epub 2022 Nov 16.
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