Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib

Trial details

Who runs it

Boston Medical Center

Trial code

NCT03591770

Record updated

21 February 2025

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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; Patient has a history of ulcerative colitis (UC) diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria; 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: Previous receipt of any HZ vaccine; Patient has received immunoglobulin therapy or blood products with the past month; Allergy to zoster vaccine or a component of the vaccine; Other underlying chronic medical conditions that could affect immunogenicity to vaccines (rheumatoid arthritis, psoriasis etc.); History of herpes zoster infection or post herpetic neuralgia; Patient cannot or will not provide written informed consent; Patient is on a non-licensed or experimental immunomodulator; Patient is on methotrexate; Currently pregnant.

ClinicalTrials.gov NCT03591770