Inflammatory bowel disease Digestive System
Conditions
Interventions
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
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The geometric mean concentration of anti-glycoprotein E antibody at days 30-48 (post second vaccine dose) in IBD patients pausing JAK-inhibitor therapy in comparison with patients continuing JAK-inhibitor therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunogenicity endpoints: 1. The vaccine response rate (VRR) of participants in the JAK-inhibitor therapy pausing arm (defined as 4-fold increase in anti-glycoprotein E antibody) compared to the control arm at 30-48 days post second vaccine dose. 2. The VRR in the JAK-inhibitor therapy pausing arm (defined as 4-fold increase in anti-glycoprotein E antibody) compared to the control arm at 335-425 days post second vaccine dose. 3. The geometric mean concentration of anti-glycoprotein E antibody at 335 to 425 days (post second vaccine dose) in IBD patients pausing JAK-inhibitor therapy in comparison with patients continuing JAK-inhibitor therapy. 4. T cell responses measured by flow cytometry at days 30-48 (post second vaccine dose) in IBD patients pausing JAK-inhibitor therapy in comparison with patients continuing JAK-inhibitor therapy. 5. T cell responses measured by flow cytometry at 335-425 days (post second vaccine dose) in IBD patients pausing JAK-inhibitor therapy in comparison with patients continuing JAK-inhibitor therapy. Safety/Reactogenicity endpoints : 1. The rate of adverse events in IBD patients pausing JAK-inhibitor therapy and in patients continuing JAK-inhibitor therapy. 2. The rate of serious adverse events in IBD patients pausing JAK-inhibitor therapy and in patients continuing JAK-inhibitor therapy. 3. The rate of IBD flares in patients pausing JAK-inhibitor therapy and in patients continuing JAK-inhibitor therapy. 4. The rate of major IBD related adverse events (hospitalisations, IBD surgery including colectomy). 5. The rate of vaccine reactogenicity including mild (e.g. local injection site reaction) and severe (e.g. anaphylaxis) reactions to Shingrix vaccination. Time frame for safety endpoints: • for a solicited symptom timeframe is the day of vaccination and 6 additional days • for an unsolicited symptom timeframe is the day of vaccination and 29 additional days • for a SAE/pIMD and specific adverse event timeframe is the day of vaccination | — |
Countries
United Kingdom
Contacts
Public ContactMaria Moreno Morales
Outcome results
None listed