Optimizing Herpes Zoster VAccinaTion in ImmunOsuppressed patieNts with Inflammatory Bowel Disease
Inflammatory bowel disease
Following a baseline visit, participants will be instructed to either continue or pause JAK-inhibitor therapy according to their study arm allocation. The experimental intervention group will be asked to pause JAK-inhibitor therapy for seven days around Shingrix vaccination (3 days before and 3 days after) each vaccine dose. The control intervention group will be asked to continue JAK-inhibitor therapy as normal throughout the vaccination process. All participants will receive two doses of Shingrix vaccine 6-8 weeks apart according to the vaccine license. Participants will be followed up after each vaccine dose to check for IBD flares and other adverse events. Blood samples will be collected at baseline and at 30-48 days and 335-425 days after the second vaccine dose. Study follow up ends at 52 weeks after the second vaccine dose (approximately 61 weeks after study entry). Randomisation is parallel-group and open-label.
1. Adults (aged ≥18 years). 2. 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. 3. Established diagnosis of CD or UC or IBD-unclassified using standard definitions of IBD. 4. Established on JAK-inhibitor therapy (either upadacitinib, tofacitinib or filgotinib) for at least 12 weeks. 5. IBD in stable remission* and able to temporarily pause JAK-inhibitor therapy for two periods of 7 days in the opinion of patients’ hospital team without the risk of substantial increase in disease activity. 6. Able to give informed consent. 7. Willing and able to meet all protocol requirements and procedures (including pausing of JAK-inhibitor therapy). *Definition of IBD in stable remission: I. Stable remission defined as having completed 8 weeks induction with JAK-inhibitor therapy, maintained for a minimum of an additional 4 weeks, according to retrospective assessment of the patients' medical files. To be confirmed by a faecal calprotectin measurement <250 μg/g and/or colonoscopy showing no active inflammation after the end of induction and within 4 weeks of screening. II. The following clinical criteria will apply at screening: o UC: PRO2 ≤ 1 with Rectal Bleeding score = 0 and Stool Frequency score ≤ 1. o CD: A modified$ Harvey Bradshaw Index (HBI) score <5. ^Calprotectin result signifying remission is assay specific. <250 μg/g used here as indicative of assay used at Imperial College Healthcare NHS Trust. $HBI without the ‘abdominal mass’ question.
1. Previous receipt of any HZ vaccine including Shingrix. 2. History of a confirmed anaphylactic reaction to any component of the vaccine. 3. History of herpes zoster or post herpetic neuralgia within the past year. 4. Primary reason for JAK-inhibitor therapy is a non-IBD immune mediated inflammatory disorder (e.g. for rheumatoid arthritis or psoriasis). Patients who are receiving JAK-inhibitor for IBD and also have other immune mediated inflammatory disorders may be included. 5. Currently receiving other immunosuppressive drug in addition to JAK-inhibitor therapy (N.B. 5-ASA therapies are not considered immunosuppressive). List to include: • Adalimumab • Infliximab • golimumab • certolizumab • vedolizumab • ustekinumab • Risankizumab • mirikizumab • guselkumab • etrasimod • ozanimod • mycophenolate • tacrolimus • thalidomide • ciclosporin. • cyclophosphamide. • hydroxychloroquine. • leflunomide. • methotrexate. 6. Current use of oral or intravenous steroids (dose equivalent to >Prednisolone 10mg od) within 30 days. 7. Patient has received polyclonal immunoglobulin therapy or blood products within the last year. 8. Receiving cancer chemotherapy or immunotherapy within last 6 months. 9. Patient is currently pregnant or planning pregnancy, or currently breastfeeding. 10. Already participating in a CTIMP (clinical trial of an investigational medicinal product).