Withdraw Drug in Stable IgG4-Related Disease

Study Overview
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Brief Summary
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Evaluation and prediction of relapse risk after glucocorticoid or immunosuppressant withdrawal in patients with stable IgG4 related disease: a prospective cohort study from china.

Detailed Description
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IgG4-related disease (IgG4-RD) is a chronic autoimmune disease with a relapsing-remitting course. For patients in remission, glucocorticoid (GC) and immunosuppressant are used to be maintained for a long time in fear of disease flare. Long-term GC and immunosuppressant could bring a lot of side-effects and economic burden. Whether and when patients with stable disease should withdraw GC or immunosuppressant? How about the relapse risk respectively? What are the risk factors for disease flare? All the above remain unclear. The aim of this study is to explore the relapse risk after GC or immunosuppressant withdrawal in IgG4-RD patients with stable disease and to establish a predictive model for risk stratification. Meanwhile the investigators aim to testify the effects of immunosuppressant in preventing IgG4-RD relapse. This study is a prospective cohort clinical trial.

Official Title
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Evaluation and Prediction of Relapse Risk After Glucocorticoid and Immunosuppressant Withdrawal in Patients With Stable IgG4 Related Disease: An Open-labeled Multi-centric Randomized Controlled Study From China

Conditions
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Autoimmune Diseases

Intervention / Treatment
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* Drug: Drug free, IS monotherapy and GC combined with IS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must meet the following diagnostic criteria of IgG4RD (2011): 1)Swelling, sclerosing and inflammatory involvement of one or more organ, including sclerosing pancreatitis, sialadenitis (Mikulicz disease), sclerosing cholangitis, inflammatory pseudotumors, retroperitoneal or mediastinal fibrosis, interstitial nephritis, hypophysitis, sclerosing dacryoadenitis, inflammatory aortic aneurysm, lymphadenopathy, or other inflammatory conditions; 2)Elevated serum IgG4 (>1.35 g/L); 3)Histopathologic features of fibrosis and/or lymphocytic and polyclonal plasma cell infiltration (and IgG4+ plasma cells on immunohistology when performed). Patients fulfill 1)+2)+3) are diagnosed as definite IgD4RD, 1)+2): possible IgG4RD; 1)+3): probable IgG4RD. exclusion of other diseases. Disease stabilized more than one year (Responder Index < 2 points) Dose of Glucocorticoid(GC): prednisone (or equivalent) ≤ 7.5mg/d for more than 6 months Immunosuppressant: one of the following drugs, the same dose maintain at least 3 months (Mycophenolate mate <= 1g/d or Leflunomide <=20mg/d or Methotrexate <=12.5mg/w or Azathioprine <=100mg/d). Exclusion Criteria: Patient was diagnosed other connective tissue diseases Patient with tumor Women during pregnancy or planning pregnancy Patient with active infections, including HIV, HCV, HBV, TB, etc. Patient with severe irreversible organ damage Active IgG4-RD, responder index >= 2 points Stable condition less than one year. Patient with two or more immunosuppressive agents. Biological agents (such as CD20 monoclonal antibody and TNF-a inhibitor) have been used for half a year before admission. Patient with IgG4-RD recurrence during hormone reduction in the past.

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 |
| --- | --- |
| Experimental: Drug free<br>Arm A: Drug free Glucocorticoid（GC）is tapered and stopped in 8 weeks(GCs at a dose of ≤ 2.5 mg of prednisone or equivalent for treatment of adrenal insufficiency) . Immunosuppressant is also tapered and discontinues in 8 weeks. | Drug: Drug free, IS monotherapy and GC combined with IS<br>* Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).<br>|
| Experimental: IS monotherapy<br>Arm B: Immunosuppressant only Glucocorticoid（GC）is tapered and stopped in 8 weeks. The same type and dosage of immunosuppressive agent before admission, including Mycophenolate mate(<= 1g/d) or Leflunomide (<=20mg/d) or Methotrexate (<=15mg/w) or Azathioprine (<=100mg/d) | Drug: Drug free, IS monotherapy and GC combined with IS<br>* Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).<br>|
| Experimental: GC combined with IS<br>Arm C: GC+Immunosuppressant Both Glucocorticoid(GC) (no more than 7.5mg/d) and immunosuppressant are kept as maintaining dose. | Drug: Drug free, IS monotherapy and GC combined with IS<br>* Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).<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 among three groups. | Clinical recurrence definition: any item of IgG4-RD Responder Index >=2，new organ involvement; with or without elevated serum IgG4 levels. Serum recurrence definition: Serum IgG4 level was higher than baseline level, IgG4-RD Responder Index was higher than or equal to 1 point, without clinical symptom or imaging deterioration. | One and half year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of IgG4-RD Responder Index | According to IgG4-RD responder Index Validation Study (Version: 13, December, 2015) | One and half year | 
| The changes of serum IgG4 levels | Level of serum IgG4(mg/dL) | One and half year | 
| The changes of serum IgG level | Level of serum IgG(g/L) | One and half year | 
| The changes of serum hsCRP level | Level of serum high-sensitivity C-reactive protein level(mg/L) | One and half year | 
| The changes of ESR | Serum erythrocyte sedimentation rate(mm/h) | One and half year | 
| The percentages of adverse events | Adverse effect of drugs | One and half year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulin G4-Related Disease