Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab

Phase 4

Completed

Conditions: Herpes Zoster
Inflammatory Bowel Diseases
Ulcerative Colitis
Crohn Disease

Interventions: Biological: Shingrix

Registration Number: NCT03798691

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract(1) affecting 1.6-3.1 million people in the United States. Patients with IBD are treated with immunosuppressants that increase their risk of herpes zoster (HZ), also known as shingles.

Those with IBD have a two-fold increased risk for HZ compared to age matched controls. Because most IBD patients are treated with systemic immunosuppressants, which are an independent risk factor for HZ, the live attenuated HZ vaccine was not recommended. However, the release of the new inactivated HZ vaccine, Shingrix (GlaxoSmithKline), presents new opportunities for preventive care.

Detailed Description: The purpose of this study is to determine the immunogenicity of the herpes zoster subunit vaccine in inflammatory bowel disease patients on vedolizumab compared to those on anti-tumor necrosis factor (TNF) monotherapy.

The study will evaluate humoral and cell mediated immunity in patients with IBD on vedolizumab who receive the two-dose herpes zoster vaccine. The investigators will evaluate short term, one month after second vaccination dose and sustained immunogenicity at 6 and 12 months post vaccination.

The central hypothesis of this proposal is that IBD patients on vedolizumab should be able to mount a normal vaccine response comparable to those on anti-TNF monotherapy who might benefit from a third dose of the subunit vaccine as has been evaluated in HIV and transplant populations. The hypothesis is that IBD patients on vedolizumab will be able to mount a superior response to those on anti-TNF therapy. A recent study showed that hepatitis B vaccine immunogenicity was not affected by vedolizumab.

The study population will include adult patients aged 50 or older with IBD(diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at University of Wisconsin Hospital and Clinics or Boston Medical Center. There is no randomization or use of placebo in this study. Two study groups (each containing 15 subjects) will be established Group A: Patients with IBD on anti-TNF monotherapy and Group B patients with IBD on vedolizumab monotherapy.

Methods: Eligible patients with IBD will be recruited from the University of Wisconsin Hospital and Clinics or from Center for Digestive Diseases at Boston Medical Center.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

Inclusion Criteria

Patient is between the ages of 18-70 years, inclusive.
History of primary varicella infection (chicken pox) Confirmed by a previous history of positive varicella zoster virus (VZV) Immunoglobulin G antibody or history of chicken pox
Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria.
Patient is receiving one of the following treatments for their IBD Group A: Anti-TNF monotherapy (adalimumab, certolizumab, golimumab, infliximab) Group B: Vedolizumab monotherapy
Patient has been on stable treatment for IBD for at least three months.

Exclusion Criteria

Previous receipt of any HZ vaccine
Allergy to zoster vaccine or a component of it
Other underlying chronic medical condition that could affect immunogenicity to vaccines (rheumatoid arthritis, etc.)
History of herpes zoster or post herpetic neuralgia within the past year.
Patient cannot or will not provide written informed consent.
Patient is being administered immunomodulators currently or within the past three months
Patient has been taking any dose of oral or intravenous steroids within 30 days prior to immunization.
Patient has received polyclonal immunoglobulin therapy or blood products within the last year.
Patient is pregnant per self-reporting or older than age 70 years
Unable to provide appropriate informed consent due to being illiterate or impairment in decision-making capacity.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti-TNF monotherapy	Shingrix	Patients with IBD on Anti-TNF monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
Vedolizumab	Shingrix	Patients with IBD on vedolizumab monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.

Primary Outcome Measures

Name	Time	Method
Change in Cell Mediated Immunity	It will be measured from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization.	The primary objective will be the change in cell mediated immunity (CMI) as measured by ELISPOT from pre-immunization to one month after receiving second dose of vaccine.

Secondary Outcome Measures

Name	Time	Method
Percent of Participants With Sustained Cell Mediated Immunity Measured Via ELISPOT After Immunization.	Baseline to 6 months post-immunization 2nd dose of vaccine.	Sustained change in CMI at 6 months will be assessed after receiving a second dose of booster vaccine post-immunization. CMI will be measured via ELISPOT
Percent of Participants With a Change in Antibody Concentration Post Immunization	pre-immunization to one month 2nd dose post-immunization	A secondary outcome will be the change in varicella zoster virus (VZV) antibody concentration comparing pre-immunization to post immunization antibody concentration.
Percent of Participants With a Change in Antibody Concentration That is Sustained at 6 Months	Baseline to 6 months post-immunization	Sustained change in VZV antibody concentration at 6 months after receiving a second dose of booster vaccine post-immunization will be assessed.
Number of Participants Who Experienced Vaccine Related Adverse Events After Dose 1	Dose 1 (Month 0)	To evaluate for adverse effects following immunization patients will receive phone calls from study personnel to ascertain vaccine-related adverse effects. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
Number of Participants Who Experienced Vaccine Related Adverse Events After Dose 2	Dose 2 (anytime from Month 2 to Month 6)	To evaluate for adverse effects following immunization patients will receive phone calls from study personnel to ascertain vaccine-related adverse effects. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
Number of Participants Experiencing a Change in Disease Activity Post Immunization Reported	at the baseline visit and one month after receipt of each vaccine	The Simple Clinical Colitis Activity Index (SCCAI) will be used to measure disease activity. It is a questionnaire with six subscore topics with scores defined by UC signs and symptoms from 0 to 4 for a range of scores from 0 to 17. Total scores are interpreted as: Remission = score of 0 to 4 points, Mild Activity = score of 5 to 7 points, Moderate Activity = Score of 8 to 16 points, and Severe Activity = Score of \> 16 points. Number of participants experiencing a change will be reported.