Safety and Tolerability of Herpes Zoster Vaccine in Patients With Rheumatoid Arthritis Immunized Prior to Biologics and Tofacitinib Therapy Initiation
试验速览
- 阶段
- 4 期
- 入组人数
- 87
- 试验地点
- 3
- 主要终点
- Number of patients with Hypersensitivity
研究概览
简要总结
The reactivation of varicella zoster virus (VZV) (herpes zoster (HZ)) is of substantial public health concern. Updated ACR recommendations for RA treatment suggest that RA patients aged ≥ 50 years should be vaccinated before receiving biologic or tofacitinib therapy. The Investigators therefore propose a prospective study to evaluate the safety, tolerability, and immunogenicity of a zoster vaccine (Zostavax) in patients with RA, administered at least 2 weeks prior to initiation of anti-TNF biologic and tofacitinib therapy for RA.
This is a 6-week open-label prospective multi-center study evaluating the safety, tolerability, and immunogenicity of Zostavax vaccine in the RA population prior to initiation of biologic/tofacitinib therapy for RA. VZV-specific immune response to vaccine in RA patients will be compared to healthy control subjects ≥ 50 years immunized with Zostavax.
详细描述
Safety and Tolerability of Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis Immunized prior to biologics and tofacitinib therapy initiation Background The reactivation of varicella zoster virus (VZV) (herpes zoster (HZ)) is of substantial public health concern. Its predilection for the elderly and immunosuppressed make it an important cause of morbidity, causing pain, depression, and long-term disability in the form of post-herpetic neuralgia. The risk of HZ is increased by 1.5 to 2 times in patients with rheumatoid arthritis (RA) compared with the general population.This increase has been attributed to both the underlying disease process and treatments for RA, in particular, corticosteroids, TNFα blocking agents, rituximab, and tofacitinib.
A live attenuated zoster vaccine, administered as a single subcutaneous injection, reduces HZ risk by 70% and 51% among immunocompetent individuals 50 to 59 years and 60 years and older in 2 randomized blinded trials, respectively.
Updated ACR recommendations for RA treatment suggest that RA patients aged ≥ 50 years should be vaccinated before receiving biologic or tofacitinib therapy. Yet, the real world data proves that only minority of RA patients initiating biologic therapy are vaccinated for herpes zoster.
The safety concern is that these individuals may develop varicella infection from the vaccine virus strain. Recently, zoster vaccine safety, tolerability, and immunogenicity were prospectively tested in patients on chronic low-medium dose of corticosteroid therapy. Zoster vaccine was generally well tolerated and immunogenic in this patient population.
Based on the VZV incubation period, the first 42 days following vaccination was chosen as the primary safety risk window in the Shingles Prevention Study, a randomized blinded trial that preceded the FDA approval of the vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
- •Patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA scheduled for a biologic or small molecule therapy (80% candidates for etanercept or tofacitinib therapies.)
- •Only subjects who are ≥ 50 years old will be administered the zoster vaccine.
- •Subjects who are willing and able to comply with scheduled visits and other study procedures
- •Patients on biologics may participate after a washout period as indicated below :
- •Etanercept : 2 weeks
- •Infliximab, Golimumab, Adalimumab : 35 days
- •Tocilizumab and Abatacept SC : 2 weeks
- •Tocilizumab and Abatacept IV : 35 days
排除标准
- •History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.
- •Previous vaccination with any VZV-containing vaccine.
- •Any type of malignancy, ongoing chemotherapy or radiation therapy.
- •Patients who underwent solid organ transplantation.
- •Patients with AIDS or clinical manifestations of HIV
- •Patients treated with a TNFa inhibitor at the time of recruitment or patients within a year of rituximab administration.
- •Patients receiving daily corticosteroid therapy with a dose ≥10 mg/day of prednisone (or equivalent) for ≥ 14 days and/or methotrexate at the dose above 0.4 mg per kg per week.
- •Patients with an active herpes zoster infection or previous herpes zoster less than 6 months before recruitment.
- •Vaccination with any live vaccine within 4 weeks prevaccination, any inactivated vaccine within 7 days prevaccination, or either during the study period.
- •Blood products transfusion within 5 months prior to vaccination through the study period.
- •Patients with active tuberculosis.
- •History of Guillain-Barre Syndrome
- •for healthy arm: Inclusion subjects who are ≥ 50 years old will be administered the zoster vaccine.
- •History of past or present autoimmune diseases
- •History or current use of immunosuppressive drugs
- •History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine.
- •.Previous vaccination with any VZV-containing vaccine.
- •Any type of malignancy, ongoing chemotherapy or radiation therapy.
- •History of underwent solid organ transplantation.
- •Active herpes zoster infection or previous herpes zoster less than 6 months before recruitment.
- •Vaccination with any live vaccine within 4 weeks prevaccination, any inactivated vaccine within 7 days prevaccination, or either during the study period.
- •Blood products transfusion within 5 months prior to vaccination through the study period.
结局指标
主要结局
Number of patients with Hypersensitivity
时间窗: 6 weeks
collecting number of patients with hypersensitivity adverse reactions defined as: Any immediate systemic reactions such as anaphylactic reaction, fever, low blood pressure, drug induced rash or urticaria, nausea and vomiting, diarrhea data will be collected at the visit of injection administration, and by phone call 2 weeks past the vaccination
Number of patients with Injection site adverse reactions
时间窗: 6 weeks
collecting number of patients with injection site adverse reactions defined as: Local pain/erythema/swelling/pruritus/warmth/hematoma/induration will be assessed by the investigators at follow up visit, and will be asked by phone call.
number of patients with Post vaccination non-injection-site zoster-like and varicella-like rashes
时间窗: 6 weeks
collecting number of patients with non-injection-site zoster-like and varicella-like rash will be defined as adverse reaction. will be assessed by investigator by phone follow up and at 6 weeks follow up meeting.
Number of patients with Post vaccination herpes zoster occurrence
时间窗: 6 weeks
collecting number of patients with Post vaccination herpes zoster occurrence will be defined as adverse reaction. will be assessed by investigator by phone follow up and at 6 weeks follow up meeting.
次要结局
- Immunogenicity measured by varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA)(6 weeks)
- Tender and Swollen Joint Count (28 joint count)(6 weeks)
- Patient Assessment of Arthritis Pain(6 weeks)
- Physician Global Assessment of Arthritis(6 weeks)
- Health Assessment Questionnaire - Disability Index (HAQ-DI)(6 weeks)
- Patient Global Assessment of Arthritis(6 weeks)