Vaccination in Patients With Inflammatory Rheumatic Diseases. The Impact of Anti-rheumatic Treatments on the Immunogenicity of Herpes-zoster Vaccine (Shingrix) and Protection Against Infection (HZ-REUMA)
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 发起方
- Region Skane
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Pre-and post-vaccination anti-gE antibody levels (geometric mean antibody levels, GML) in patients and controls
研究概览
简要总结
The purpose of HZ-REUMA study is explore vaccine response and protection against shingles (herpes zoster, HZ) after vaccination with two doses of Shingrix in immunosuppressed patients with inflammatory rheumatic diseases (IRD) compared to immunocompetent patients with IRD (controls).
Hypothesis:
The immunological disturbance as part of the rheumatic disease in combination with different immunomodulating treatments may impair vaccine response to non-live HZ vaccine (Shingrix) and thereby lead to an insufficient protection against infection.
Primary objective (outcome)
- The impact of modern anti-rheumatic treatments including synthetic disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate and different biological treatments (anti-TNF, anti IL6r, anti-IL12/23/17, anti-CD20, anti-BlyS, anti-INFERON treatment, or targeted DMARDs (JAK-inhibitors) on antibody response elicited by two doses of subunit vaccine against herpes zoster (HZ) administrated 1-2 months apart in patients with IRD.
Secondary outcomes 2. The numbers and frequency of antigen specific CD4 2+ T cells expressing ≥2 or more activation markers (TNFalpha, INF-gama, interleukin-2 or CD40ligand) 3. Long-term immunogenicity of two doses of Shingrix in immunosuppressed patients with IRD measured 3 and 5 after vaccination 4. the tolerability of the vaccine, the impact on existing rheumatic disease, and possible association with onset of new autoimmune diseases 5. if vaccination against herpes zoster protects against infections in patients with inflammatory rheumatic diseases
Study Population Adult patients (18 years and older) with a clinically diagnosed inflammatory rheumatic disease and regularly followed at Skåne University Hospital, section for rheumatology in Lund/Malmö, Sweden are eligible for the study and will be offered vaccination free of charge. Control group comprises adult individuals with known inflammatory rheumatic disease without immunosuppressive treatment except for low dose prednisone (max 5 mg daily) .
Inclusion criteria:
- age ≥18 years (patients)
- regular follow up at Skåne University Hospital, section for rheumatology Lund/Malmö due to an inflammatory rheumatic disease (patients)
- receive active treatment with disease modifying anti-rheumatic drugs (DMARDs) such conventional synthetic (cs), biologic (b) or targeted synthetic (ts) DMARDs or patients without active immunosuppressive treatment (controls)
Exclusions criteria
- age <18 years (patients)
- pregnancy (women of childbearing potential, WOCBP, are not excluded since all patients using DMARDs are advised to use a safe and effective contraceptive method)
- allergy/intolerability of any component in the vaccine
- active infection inclusive herpes zoster (shingles)
- received Shingrix vaccine previously
- ongoing treatment with any immunosuppressive drug for the other diseases Target enrolment/sample size: 240. Study start date: December, 17 2024- June 30, 2029
详细描述
Patients with inflammatory rheumatic diseases (IRD) such as rheumatoid arthritis (RA), SLE, spondyloarthropathies, systemic vasculitis or systemic sclerosis (Granulomatosis with polyangiitis, GPA; Eosinophilic granulomatosis with polyangiitis, EGPA, Giant Cell Arteritis, GCA), systemic sclerosis or other inflammatory systemic disease) have an increased morbidity and mortality in infections. These infections include the numerous vaccine-preventable diseases such as herpes zoster (HZ). Vaccination is a cost-effective measure to prevent an infection. However, several studies have reported an impaired response to common vaccinations among immunosuppressive patients with IRD. The underlying mechanisms are not entirely known. The Centre for Disease Control (CDC) Advisory Committee for Immunization Practice (ACIP) as well as the European League Against Rheumatism (EULAR) and Swedish authorities (The Public Health Agency of Sweden) recommend vaccination against HZ to the risk groups. Majority of patients with IRD are treated with potent immunosuppressive drugs and thereby belong to the target group for HZ vaccine. Data on the immunogenicity, tolerability of a non-live, subunit vaccine against HZ (Shingrix) among immunosuppressed patients with IRD is limited. The overall aim of this research project is to study antibody and T cells response and tolerability of two doses of subunit HZ vaccine (Shingrix) in immunosuppressed patients with IRD compared to IRD patients without active immunosuppressive treatment (with exception for prednisolone orally in a maximal daily dose of 5 mg).
Hypothesis The immunological disturbance as part of the rheumatic disease in combination with different immunomodulating treatments may impair antibody and T cells vaccine response but vaccination is still expected to generate a "satisfactory immune response".
Main objective (outcome)
To study:
- The impact of modern anti-inflammatory treatments including synthetic disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate and different biological treatments (anti-TNF, anti IL6r, anti IL12/23/17, anti CD20, JAK-inhibitors, anti-BlyS, anti-INF, or targeted DMARDs (JAK-inhibitors) on antibody response elicited by two doses of subunit vaccine against herpes zoster (HZ) administrated 1-2 months apart in patients with IRD Secondary objectives (outcomes)
- The numbers and frequency of antigen specific CD4 2+ T cells expressing ≥2 or more activation markers
- Long-term immunogenicity (measured as GML of anti-gE antibodies and numbers and frequency of antigen specific CD4 2+ T cells expressing ≥2 or more activation markers 3 and 5 years after vaccination with two doses of Shingrix vaccine
- the tolerability of the vaccine including the impact on existing rheumatic disease (increased activity/flare/possible association with onset of new potential immune-mediated diseases (pIMD) or herpes zoster case during the study period, see the enclosed algorithm.
- if vaccination against herpes zoster protects against infections in patients with inflammatory rheumatic diseases
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (age 18 years and older) with clinically diagnosed inflammatory rheumatic disease who are regularly followed at Skåne University Hospital, section for rheumatology in Lund and Malmö, Sweden are eligible for the study and will be offered vaccination with 2 doses of Shingrix free of charge. Control group comprises adult patients with inflammatory rheumatic diseases not receiving immunosuppressed drugs but receive 2 doses of Shingrix.
- •age ≥18 years
- •has diagnosed an inflammatory rheumatic disease
- •has a regular follow up at Dept of rheumatology, Skåne University Hospital Lund/Malmö
- •receives active treatment with disease modifying antirheumatic drugs (DMARDs) such conventional synthetic (cs), biologic (b) or targeted synthetic (t) DMARDs [patients in the study] or no active treatment with s/b/t DMARDs with exception of daily prednisolone dose of max 5 mg [controls in the study]
- •a safe preventive method for women before menopause
- •is able to sign a consent
排除标准
- •age <18years
- •pregnancy (women of childbearing potential, WOCBP need to declare the using a safe contraceptive method)
- •allergy/intolerability of any component in the vaccine
- •acute disease and/or fever at the time of vaccination. Fever is defined as temperature ≥ 37.5°C by oral route. (The preferred route for recording temperature in this study will be oral). Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator
- •received Shingrix vaccine previously
- •ongoing treatment with any immunosuppressive drug for other disease with exception for prednisolone in a daily dose corresponding max 5 mg before the inclusion
- •participates or has participated in the other interventional clinical study within 3 months before the inclusion
- •taking concurrently medication which is not approved in EU
研究组 & 干预措施
all participants will be vaccinated with two doses Shingrix vaccine
all participants will be vaccinated but the difference in the antibody and T cells responses to vaccination will be compared between the grupp of patients treated with immunomodulating drigs and patients not receiving such treatments
干预措施: Shingrix (Drug)
all participants will be vaccinated with two doses Shingrix vaccine
all participants will be vaccinated but the difference in the antibody and T cells responses to vaccination will be compared between the grupp of patients treated with immunomodulating drigs and patients not receiving such treatments
干预措施: vaccination with 2 doses of Shingrix vaccine (Drug)
结局指标
主要结局
Pre-and post-vaccination anti-gE antibody levels (geometric mean antibody levels, GML) in patients and controls
时间窗: before vaccination and 4-6 vecks after the second vaccine dose
Measurement of pre-and post-vaccination anti-gE antibody (g/L) in patients and controls which will be used for calculating the proportion of individuals in different treatments group and controls with ≥4-fold increase in anti-gE antibody measured 4-6 weeks following the second vaccine dose (vaccine response rate)
次要结局
- Number and function of antigen (vaccine) specific T cells(before vaccination and 4-6 weeks after second vaccine dose)
- long-term immunogenicity(3 and 5 years after inclusion)
- the tolerability of the vaccine(from inclusion to 6 months after the inclusion of last patient)
- number of HZ infections in vaccinated individuals(from 1 months after the second vaccine dose to the study end 2034)