Clinical Trial: Safety and Tolerability of Herpes Zoster Vaccine Rheumatologic Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety and Tolerability of Herpes Zoster Vaccine in Patients With Rheumatoid Arthritis Immunized Prior to Biologics and Tofacitinib Therapy Initiation

Brief Summary:

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.


Detailed Summary:

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
Sponsor: HaEmek Medical Center, Israel

Current Primary Outcome:

  • Number of patients with Injection site adverse reactions [ Time Frame: 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 Hypersensitivity [ Time Frame: 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 Post vaccination non-injection-site zoster-like and varicella-like rashes [ Time Frame: 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 [ Time Frame: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Immunogenicity measured by varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) [ Time Frame: 6 weeks ]
    of 15 cc blood only will be taken at two visits: pre-vaccination and post-vaccination (6 weeks). Serum will be separated, aliquoted and stored frozen at -20°C until analysis. The serum samples will be stored and tested in the TASMC Laboratory for Arthritis Research. VZV antibody titers will be measured by commercially available ELISA kits. Any other analyses of the serum samples in the future will only be performed after obtaining permission from the institutional ethics committee, as required by law. No genetic test will be performed. The serum samples will not be taken outside of the Tel Aviv Medical Center, unless specific permission is obtained from the institutional ethics committee in the future. Samples of 15 cc blood only will be taken at two visits: pre-vaccination and post-vaccination (6 weeks). Serum will be separated, aliquoted and stored frozen at -20°C until analysis. The serum samples will be stored and tested in the TASMC Laboratory for Arthritis Research. VZV antibody
  • Tender and Swollen Joint Count (28 joint count) [ Time Frame: 6 weeks ]

    Twenty-eight (28) joints will be assessed by a physician to determine the number of joints that are considered tender/painful. The response to pressure/motion on each joint will be assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial joints). These joints will be further assessed for swelling using the same scale.

    The 28 joints to be assessed are the shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees. Artificial joints will not be assessed.

  • Patient Assessment of Arthritis Pain [ Time Frame: 6 weeks ]
    Participants will assess the severity of their arthritis pain using a 100 mm visual analog scale (VAS) placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponds to the magnitude of their pain.
  • Patient Global Assessment of Arthritis [ Time Frame: 6 weeks ]
    Participants will answer the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" The subject's response will be recorded using a 100 mm VAS
  • Physician Global Assessment of Arthritis [ Time Frame: 6 weeks ]
    The physician will assess how the subject's overall arthritis appears at the time of the visit. This is an evaluation based on the subject's disease signs, functional capacity and physical examination, and should be independent of the Patient's Global Assessment of Arthritis. The Investigator's response will be recorded using a 100 mm VAS.
  • Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: 6 weeks ]
    The HAQ-DI assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities.13 Each activity category consists of 2-3 items. For each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 0 representing "no difficulty," 1 as "some difficulty," 2 as "much difficulty," and 3 as "unable to do". Any activity that requires assistance from another individual or requires the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. The form should then be checked by the site staff for completeness.


Original Secondary Outcome: Same as current

Information By: HaEmek Medical Center, Israel

Dates:
Date Received: January 1, 2017
Date Started: January 2017
Date Completion: May 2019
Last Updated: February 5, 2017
Last Verified: February 2017