Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Colitis, Colitis, Irritable Bowel Syndrome (IBS), Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 50 - Any |
| Updated: | 3/28/2019 |
| Start Date: | April 2019 |
| End Date: | August 2020 |
| Contact: | Sharmeel K Wasan, MD |
| Email: | sharmeel.wasan@bmc.org |
| Phone: | (617) 638-6116 |
The Immunogenicity and Safety of Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
Patients with ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), have been
shown to be at increased risk of developing certain infections, such as shingles from the
Herpes Zoster (HZ) virus, as a result of their underlying disease. Patients with UC are also
often treated with immunosuppressants, and research has shown that IBD patients on
immunosuppressants have an impaired immune response to vaccination in comparison to
immunocompetent controls. Because UC patients are often treated with immunosuppressants, the
live HZ vaccine was not recommended in these patients. Shingrix, however, is a new
inactivated vaccine recently approved by the FDA for prevention of HZ in adults age 50 and
older, and Shingrix should be safe to administer in IBD patients because it does not contain
live HZ virus. Data on efficacy of the Shingrix vaccine also appears promising in
immunocompromised patients.
Tofacitinib citrate (Xeljanz), an immunosuppressant that works by inhibiting the Janus kinase
pathway, is currently approved for treatment of certain inflammatory diseases such as
rheumatoid arthritis and psoriasis. The drug is currently awaiting FDA-approval for use in
moderate-to-severe UC but has been used off-label in various settings. Notably, tofacitinib
was associated with an increased risk of HZ in patients with rheumatoid arthritis and
psoriasis.
The research hypothesis is that UC patients on tofacitinib will mount an adequate response
and that the response will be slightly diminished compared to non-immunosuppressed IBD
patients, comparable to those on anti-tumor necrosis alpha (anti-TNF) monotherapy, and
superior to those on anti-TNF therapy in combination with a thiopurine. Strong cell mediated
immunity is shown to prevent reactivation of HZ, and demonstrating a robust immune response
to Shingrix may serve as a surrogate for a reduced risk of developing shingles and might
alleviate prescribers' concerns regarding the use of tofacitinib. The results will also serve
as pilot data to inform larger future studies evaluating the actual risk of developing
shingles in patients on tofacitinib who receive Shingrix.
shown to be at increased risk of developing certain infections, such as shingles from the
Herpes Zoster (HZ) virus, as a result of their underlying disease. Patients with UC are also
often treated with immunosuppressants, and research has shown that IBD patients on
immunosuppressants have an impaired immune response to vaccination in comparison to
immunocompetent controls. Because UC patients are often treated with immunosuppressants, the
live HZ vaccine was not recommended in these patients. Shingrix, however, is a new
inactivated vaccine recently approved by the FDA for prevention of HZ in adults age 50 and
older, and Shingrix should be safe to administer in IBD patients because it does not contain
live HZ virus. Data on efficacy of the Shingrix vaccine also appears promising in
immunocompromised patients.
Tofacitinib citrate (Xeljanz), an immunosuppressant that works by inhibiting the Janus kinase
pathway, is currently approved for treatment of certain inflammatory diseases such as
rheumatoid arthritis and psoriasis. The drug is currently awaiting FDA-approval for use in
moderate-to-severe UC but has been used off-label in various settings. Notably, tofacitinib
was associated with an increased risk of HZ in patients with rheumatoid arthritis and
psoriasis.
The research hypothesis is that UC patients on tofacitinib will mount an adequate response
and that the response will be slightly diminished compared to non-immunosuppressed IBD
patients, comparable to those on anti-tumor necrosis alpha (anti-TNF) monotherapy, and
superior to those on anti-TNF therapy in combination with a thiopurine. Strong cell mediated
immunity is shown to prevent reactivation of HZ, and demonstrating a robust immune response
to Shingrix may serve as a surrogate for a reduced risk of developing shingles and might
alleviate prescribers' concerns regarding the use of tofacitinib. The results will also serve
as pilot data to inform larger future studies evaluating the actual risk of developing
shingles in patients on tofacitinib who receive Shingrix.
The purpose of this study is to determine the immune response from the new Shingrix vaccine
in UC patients on tofacitinib monotherapy in comparison to other UC therapies. the
investigators plan to determine this by vaccinating IBD patients on (a) tofacitinib
monotherapy, (b) anti-TNF monotherapy, (c) anti-TNF combination therapy with a thiopurine, or
(d) aminosalicylates or other non-immunosuppressive therapy with the new Shingrix vaccine and
measuring markers of cell-mediated immunity before vaccination and at one and six months
after the last vaccine dose. Cell-mediated immunity will be measured with an interferon gamma
(IFNγ) enzyme linked immunospot (ELISPOT) test to assess T-cell response. Humoral immunity
will also be measured with an enzyme-linked immunosorbent assay (ELISA) kit to quantify
antibody concentrations of Varicella Zoster Virus (VZV), the pathogen that when reactivated
results in shingles.
The study population will include adult patients aged 50 or older with UC (diagnosed by
standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at
Boston Medical Center, Hospital of the University of Pennsylvania, or University of Wisconsin
Hospital and Clinics. There is no randomization or use of placebo in this study. Four study
groups (each containing 25 subjects) will be established -- 1. Group A - UC patients on
tofacitinib monotherapy. 2. Group B - UC patients receiving anti-TNF monotherapy (adalimumab,
golimumab, infliximab). 3. Group C - UC patients on an anti-TNF agent and a thiopurine
(6-mercaptopurine, azathioprine). Group D - UC patients on non-immunosuppressive therapy or
5-aminosalicylates. For each subject, 3 total samples will be collected.
Methods: Eligible patients with UC will be recruited from the Center for Digestive Diseases
at Boston Medical Center, the Hospital of the University of Pennsylvania, or the University
of Wisconsin Hospital and Clinics. Patients will be screened for participation in the study
and recruited by their primary gastroenterologist. In clinic, a handout of the risks and
benefits of the clinically indicated vaccine (Shingrix) will be given to each patient from
their primary gastroenterologist for their review. Patients will have the opportunity to opt
in or out of the study early in the consent process upon review of the handout. If a patient
elects to participate in the study, patients will sign the consent, be entered into the study
with assignment of a Subject ID number, and complete the initial study assessments:
Subject contacts:
- 1 - Baseline/Enrollment Visit 1 (Day 0): Subjects will have a comprehensive medical
history and physical exam performed, including vaccination history and all medications
over past 30 days. They will also complete a Simple Clinical Colitis Activity Index
(SCCAI) questionnaire. A baseline blood sample of approximately 20mL (4 tablespoons)
will then be obtained. If proof of past varicella infection is met by appropriate
history, subjects will receive the Shingrix vaccine indicated based on their vaccination
history as recommended by their gastroenterologist; otherwise subjects will follow-up in
1 week to review confirmatory serology results and receive vaccine if indicated. The
Shingrix vaccine will be given in a two-dose series (0.5 mL each) administered
intramuscularly -first dose at Month 0 followed by a second dose anytime between 2 and 6
months later. Subjects will be instructed to call the study team for any concerns or any
development of fever, chills, rash or other concerning symptom.
- 2- Follow up Visit 2 (approximately day 7): This visit is only needed for patients who
require serologic confirmation of past varicella infection, therefore patients who meet
proof for past varicella infection by appropriate history do not require serologic
confirmation and will NOT be scheduled for this visit. Subjects will review results of
the VZV antibody level test with their provider. If VZV antibody levels are positive,
subjects will receive the Shingrix vaccine indicated based on their vaccination history
as recommended by their gastroenterologist. Subjects will be instructed to call the
study team for any concerns or any development of fever, chills, rash or other
concerning symptom.
- 3 - Follow up Phone Call 1 (approximately day 14): Subjects will receive a follow-up
phone call to identify any adverse effects including fevers or chills, rash, and visits
to the emergency room or to their primary care physicians. They will also be reminded
about their follow up visit.
- 4 - Follow up Visit 3 (approximately day 60): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. The 2nd dose of the Shingrix vaccine will be administered.
- 5 - Follow up Phone Call 2 (approximately day 72): Subjects will receive a follow-up
phone call to identify any adverse effects including fevers or chills, rash, and visits
to the emergency room or to their primary care physicians. They will also be reminded
about their follow up visit.
- 6 - Follow up Visit 4 (approximately day 90): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. A blood sample of approximately 20mL (4 tablespoons) will then be
obtained.
- 7 - Follow up Visit 5 (approximately day 240): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. A blood sample of approximately 20mL (4 tablespoons) will then be
obtained.
The entire procedure will be identically performed at the additional sites outside of Boston
Medical Center. Subjects' duration of participation will range from 8 to 12 months, depending
on when the 2nd vaccine dose is administered.
in UC patients on tofacitinib monotherapy in comparison to other UC therapies. the
investigators plan to determine this by vaccinating IBD patients on (a) tofacitinib
monotherapy, (b) anti-TNF monotherapy, (c) anti-TNF combination therapy with a thiopurine, or
(d) aminosalicylates or other non-immunosuppressive therapy with the new Shingrix vaccine and
measuring markers of cell-mediated immunity before vaccination and at one and six months
after the last vaccine dose. Cell-mediated immunity will be measured with an interferon gamma
(IFNγ) enzyme linked immunospot (ELISPOT) test to assess T-cell response. Humoral immunity
will also be measured with an enzyme-linked immunosorbent assay (ELISA) kit to quantify
antibody concentrations of Varicella Zoster Virus (VZV), the pathogen that when reactivated
results in shingles.
The study population will include adult patients aged 50 or older with UC (diagnosed by
standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at
Boston Medical Center, Hospital of the University of Pennsylvania, or University of Wisconsin
Hospital and Clinics. There is no randomization or use of placebo in this study. Four study
groups (each containing 25 subjects) will be established -- 1. Group A - UC patients on
tofacitinib monotherapy. 2. Group B - UC patients receiving anti-TNF monotherapy (adalimumab,
golimumab, infliximab). 3. Group C - UC patients on an anti-TNF agent and a thiopurine
(6-mercaptopurine, azathioprine). Group D - UC patients on non-immunosuppressive therapy or
5-aminosalicylates. For each subject, 3 total samples will be collected.
Methods: Eligible patients with UC will be recruited from the Center for Digestive Diseases
at Boston Medical Center, the Hospital of the University of Pennsylvania, or the University
of Wisconsin Hospital and Clinics. Patients will be screened for participation in the study
and recruited by their primary gastroenterologist. In clinic, a handout of the risks and
benefits of the clinically indicated vaccine (Shingrix) will be given to each patient from
their primary gastroenterologist for their review. Patients will have the opportunity to opt
in or out of the study early in the consent process upon review of the handout. If a patient
elects to participate in the study, patients will sign the consent, be entered into the study
with assignment of a Subject ID number, and complete the initial study assessments:
Subject contacts:
- 1 - Baseline/Enrollment Visit 1 (Day 0): Subjects will have a comprehensive medical
history and physical exam performed, including vaccination history and all medications
over past 30 days. They will also complete a Simple Clinical Colitis Activity Index
(SCCAI) questionnaire. A baseline blood sample of approximately 20mL (4 tablespoons)
will then be obtained. If proof of past varicella infection is met by appropriate
history, subjects will receive the Shingrix vaccine indicated based on their vaccination
history as recommended by their gastroenterologist; otherwise subjects will follow-up in
1 week to review confirmatory serology results and receive vaccine if indicated. The
Shingrix vaccine will be given in a two-dose series (0.5 mL each) administered
intramuscularly -first dose at Month 0 followed by a second dose anytime between 2 and 6
months later. Subjects will be instructed to call the study team for any concerns or any
development of fever, chills, rash or other concerning symptom.
- 2- Follow up Visit 2 (approximately day 7): This visit is only needed for patients who
require serologic confirmation of past varicella infection, therefore patients who meet
proof for past varicella infection by appropriate history do not require serologic
confirmation and will NOT be scheduled for this visit. Subjects will review results of
the VZV antibody level test with their provider. If VZV antibody levels are positive,
subjects will receive the Shingrix vaccine indicated based on their vaccination history
as recommended by their gastroenterologist. Subjects will be instructed to call the
study team for any concerns or any development of fever, chills, rash or other
concerning symptom.
- 3 - Follow up Phone Call 1 (approximately day 14): Subjects will receive a follow-up
phone call to identify any adverse effects including fevers or chills, rash, and visits
to the emergency room or to their primary care physicians. They will also be reminded
about their follow up visit.
- 4 - Follow up Visit 3 (approximately day 60): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. The 2nd dose of the Shingrix vaccine will be administered.
- 5 - Follow up Phone Call 2 (approximately day 72): Subjects will receive a follow-up
phone call to identify any adverse effects including fevers or chills, rash, and visits
to the emergency room or to their primary care physicians. They will also be reminded
about their follow up visit.
- 6 - Follow up Visit 4 (approximately day 90): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. A blood sample of approximately 20mL (4 tablespoons) will then be
obtained.
- 7 - Follow up Visit 5 (approximately day 240): Subjects will complete a SCCAI
questionnaire, and information will be collected to identify any adverse effects
including fevers or chills, rash, and visits to the emergency room or to their primary
care physician. A blood sample of approximately 20mL (4 tablespoons) will then be
obtained.
The entire procedure will be identically performed at the additional sites outside of Boston
Medical Center. Subjects' duration of participation will range from 8 to 12 months, depending
on when the 2nd vaccine dose is administered.
Inclusion Criteria:
1. Proof of primary varicella infection (chicken pox) either by appropriate history (as
defined by ACIP) or otherwise confirmed with a positive VZV IgG antibody level
2. Patient has a history of ulcerative colitis (UC) diagnosed by standard clinical,
radiographic, endoscopic, and histopathologic criteria
3. Patient is receiving one of the following treatments for their UC:
Group A: Tofacitinib monotherapy, Group B: Anti-TNF monotherapy (adalimumab, golimumab,
certolizumab pegol, infliximab), Group C: Anti-TNF combination therapy with a thiopurine (6
mercaptopurine, azathioprine), Group D: 5-aminosalicylates or other non-immunomodulatory
therapy.
Exclusion Criteria:
1. Previous receipt of any HZ vaccine
2. Allergy to zoster vaccine or a component of the vaccine
3. Other underlying chronic medical conditions that could affect immunogenicity to
vaccines (rheumatoid arthritis, psoriasis etc.)
4. History of herpes zoster infection or post herpetic neuralgia
5. Patient cannot or will not provide written informed consent
6. Patient is on a non-licensed or experimental immunomodulator
7. Patient is on methotrexate
8. Patient has received immunoglobulin therapy or blood products with the past month
9. Currently pregnant
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