Effect of Methotrexate Discontinuation on Immunogenicity of 20-valent Pneumococcal Conjugate Vaccine (PCV20) in Patients With Autoimmune Rheumatic Diseases
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- Seroconversion Rate After Vaccination
研究概览
简要总结
This clinical trial aims to evaluate the effect of temporary methotrexate (MTX) discontinuation on the humoral immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adult patients with autoimmune rheumatic diseases (ARDs).
Key questions:
- Does suspending MTX for 2 weeks after PCV20 enhance humoral immunogenicity?
- What is the impact of MTX discontinuation on functional opsonophagocytic activity (OPA) and cellular immunity?
- What is the risk of disease flaring with MTX withdrawal?
详细描述
Patients with autoimmune rheumatic diseases (ARDs) have an increased risk of infections, including invasive pneumococcal disease, due to underlying immune dysregulation and the frequent use of immunosuppressive therapies. Pneumococcal vaccination is strongly recommended in this population; however, methotrexate (MTX), a cornerstone therapy for ARDs, has been consistently associated with reduced vaccine immunogenicity.
Evidence from randomized clinical trials in influenza and COVID-19 vaccination has demonstrated that short-term MTX discontinuation (10-14 days post-vaccination) can significantly enhance humoral immune responses. However, this strategy may be accompanied by an increased risk of mild disease flare. Importantly, no study to date has evaluated the effect of temporary MTX discontinuation on pneumococcal vaccination, representing a critical knowledge gap in the care of immunosuppressed patients.
The 20-valent pneumococcal conjugate vaccine (PCV20) represents the most comprehensive pneumococcal conjugate vaccine currently licensed, covering 20 serotypes responsible for the majority of invasive disease. Unlike polysaccharide vaccines, conjugate vaccines generate T-cell dependent immune responses, leading to higher-quality and longer-lasting protection. Yet, the immunogenicity of PCV20 in patients with ARDs under MTX therapy has not been investigated.
This randomized, double-blind, controlled clinical trial will evaluate the impact of a 2-week MTX discontinuation following PCV20 vaccination in patients with ARDs in remission or low disease activity. A total of 192 adult patients will be enrolled and randomized 1:1 to either suspend MTX for 2 weeks after vaccination or continue MTX treatment as usual.
All participants will receive one dose of PCV20 at baseline (D0). Blood samples will be collected at baseline (D0), 4 weeks post-vaccination (D28), and 6 months post-vaccination (D180). Humoral immunogenicity will be assessed by quantifying IgG antibody concentrations against 12 vaccine serotypes using multiplex Luminex assays. In addition, we will evaluate serotype-specific opsonophagocytic activity (OPA) assays to assess functional antibody responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (>=18 years ) with confirmed ARD diagnosis (e.g., RA, PsA, axial SpA, primary Sjögren's, SLE, IIM, SSc, MCTD).
- •Stable MTX dose ≥12 weeks.
- •Prednisone ≤5 mg/day.
- •Low disease activity/remission according to specific disease activity criteria.
- •Eligible for PCV20 vaccination (no prior PCV20).
排除标准
- •Anaphylaxis to vaccine components.
- •Acute febrile illness.
- •Guillain-Barré, decompensated CHF (NYHA III-IV), demyelinating disease.
- •Live virus vaccine ≤4 weeks or inactivated vaccine ≤2 weeks before.
- •Blood products in last 6 months.
- •Severe infection in last month (including pneumococcal).
- •Hospitalization at enrollment.
- •Refusal to participate or inability to complete study procedures.
研究组 & 干预措施
MTX
Participants randomized to this arm will receive one dose of the 20-valent pneumococcal conjugate vaccine (PCV20) at baseline (D0). They will continue MTX therapy without interruption during the vaccination period, maintaining their stable immunosuppressive regimen. Prednisone up to 5 mg/day and other stable background therapies will also be maintained. Blood samples will be collected at baseline (D0), 4 weeks post-vaccination (D28), and 6 months post-vaccination (D180).
干预措施: Pneumococcal Vaccine (Biological)
MTX suspension
Participants randomized to this arm will receive one dose of the 20-valent pneumococcal conjugate vaccine (PCV20) at baseline (D0). They will be instructed to discontinue methotrexate (MTX) for 2 weeks following vaccination, then resume their regular MTX regimen. Prednisone up to 5 mg/day and other stable background therapies will be maintained. Blood samples will be collected at baseline (D0), 4 weeks post-vaccination (D28), and 6 months post-vaccination (D180).
干预措施: Pneumococcal Vaccine (Biological)
结局指标
主要结局
Seroconversion Rate After Vaccination
时间窗: Day 28 (4 weeks post-vaccination).
Proportion of participants who achieve seroconversion, defined as at least a twofold increase in IgG antibody concentrations for ≥50% of PCV20 vaccine serotypes (1, 3, 4, 5, 6B, 7F, 8, 9V, 12F, 14, 19A e 23F) compared to baseline, measured by multiplex Luminex assay.
次要结局
- Frequency of Disease Flares in Rheumatoid Arthritis(Baseline through Day 28.)
- Frequency of Disease Flares in Spondyloarthritis(Baseline through Day 28)
- Frequency of Disease Flare in Myopathies(Baseline through Day 28)
- Frequency of Disease Flares in Primary Sjögren's Syndrome(Baseline through Day 28)
- Frequency of Disease Flare in Systemic Lupus Erythematosus(Baseline through Day 28)
- Frequency of Disease Flares in Psoriatic Arthritis(Baseline through Day 28)
- Frequency of Disease Flares in Behçet's Disease(Baseline through Day 28)
- Frequency of Disease Flares in Systemic Sclerosis(Baseline through Day 28)
- Adverse events(Baseline through Day 28)
- Opsonophagocytic Activity (OPA) Response(Day 0 to Day 28)
- Persistence of Humoral Immunity(Day 180 (6 months post-vaccination).)