Baricitinib Plus Glucocorticoid for Eosinophilia in IgG4-RD

Study Overview
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Brief Summary
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Evaluation of efficacy and safety of Baricitinib combined with glucocorticoid in patients of IgG4-related disease with eosinophilia.

Detailed Description
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This is a multicenter, 52-week prospective, randomized controlled study to compare the efficacy and safety of Baricitinib combined with glucocorticoid and glucocorticoid monotherapy in proliferative IgG4-RD patients with eosinophilia.

Official Title
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A Prospective, Randomized Controlled Study to Compare the Efficacy and Safety of Baricitinib Combined With Glucocorticoid and Glucocorticoid Monotherapy in Proliferative IgG4-RD Patients With Eosinophilia

Conditions
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IgG4-related Disease With Eosinophilia

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must meet the following diagnostic criteria of IgG4RD (2020): 1) and radiological features: One or more organs show diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD. In single organ involvement, lymph node swelling is omitted. 2) serological diagnosis: Serum IgG4 levels greater than 135 mg/dl. 3) diagnosis diagnosis: Positivity for two of the following three criteria: a. Dense lymphocyte and plasma cell infiltration with fibrosis. b. Ratio of IgG4-positive plasma cells /IgG-positive cells greater than 40% and the number of IgG4-positive plasma cells greater than 10 per high powered field. c. Typical tissue fibrosis, particularly storiform fibrosis, or obliterative phlebitis. Patients fulfill (1) + (2) + (3) are diagnosed as definite IgD4RD; (1) + (2): possible IgG4RD; (1) + (3): probable IgG4RD. exclusion of other diseases. Active IgG4-RD (Responder Index ≥ 2 points for each involved organ) The counts of peripheral blood eosinophil cells ≥0.75×109/L Exclusion Criteria: Patients who is not able to discontinue GC Pregnancy or breastfeeding or planning to get pregnant within 2 years Received glucocorticoids, immunosuppressants, biological agents or JAK inhibitors within 3 months Allergic to Baricitinib Concomitant other autoimmune diseases Malignancy Chronic HBV infection, latent tuberculosis, or active infection Server liver or renal dysfunction, or heart failure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Prednisolone monotherapy<br>Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months. | Drug: Prednisolone<br>* Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months.<br>|
| Experimental: Prednisolone plus Baricitinib<br>Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months. Oral Baricitinib 2mg daily for 12 months. | Drug: Prednisolone<br>* Oral prednisolone 0.6-0.8mg/kg daily for 4 weeks, then tapered and withdrawal in 4 months.<br>Drug: Baricitinib<br>* Oral Baricitinib 2mg daily for 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of recurrent rate of IgG4-RD between the two groups | Clinical recurrence definition: any item of IgG4-RD Responder Index ≥2 (without treatment), or ≥ 3 (with treatment) or new organ involvement; with or without elevated serum IgG4 levels. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time of recurrence | Clinical recurrence definition: any item of IgG4-RD Responder Index ≥2 (without treatment), or ≥ 3 (with treatment) or new organ involvement; with or without elevated serum IgG4 levels. | 0-52 weeks | 
| The changes of IgG4-related disease Responder Index | According to international multispecialty validation study of IgG4-related disease Responder Index (Version: 13, December, 2015), Responder Index ≥ 0, and higher scores mean a worse outcome. | 52 weeks | 
| The changes of blood Eosinophil cells | Percentages (%) and counts (109) of peripheral eosinophil cells | 52 weeks | 
| The changes of serum IgG levels | Level of serum IgG(g/L) | 52 weeks | 
| The changes of serum IgG4 levels | Level of serum IgG4(mg/dL) | 52 weeks | 
| The changes of serum hsCRP level | Level of serum high-sensitivity C-reactive protein level(mg/L) | 52 weeks | 
| The changes of ESR | Serum erythrocyte sedimentation rate(mm/h) | 52 weeks | 
| The percentages of adverse events | Adverse effect of drugs | 52 weeks | 
| The changes of PGA | Changes of patient global assessment from baseline, score (0-10, higher is worse) | 52 weeks | 
| The results of High-throughput analysis | The changes of results from baseline in High-throughput analysis, including GWAS, single cell sequencing of B cell receptor. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgG4-related disease, eosinophilia