Treatment Strategies for IgG4-RD Patients With Internal Organ Involvement

Study Overview
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Brief Summary
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This study has been designed as a 12-month, open-label randomized controlled clinical trial. The study aims to compare the efficacy and safety of two treatment strategies in active IgG4-RD patients with internal organ involvement during maintenance remission period: low dose mycophenolate mofetil group and leflunomide group.

Detailed Description
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60 active IgG4-RD patients with internal organ involvement are enrolled in this study and accept the combination treatment of glucocorticoids and mycophenolate mofetil in remission induction period (6 months), during which glucocorticoids are tapered regularly and discontinued in 3 months. During remission maintenance period, pateints are randomly divided into two groups at a 1:1 ratio: patients in group I are treated with low dose mycophenolate mofetil (0.5-1g/day) and patients in group Ⅱ accept the treatment of leflunomide (10-20 mg/day). Patients in two groups will be followed up for another 6 months, and clinical evaluations, laboratory tests, image examinations and IgG4-RD responder index (RI) will be recorded during follow up. The primary endpoint is the difference of relapse rate between two groups at 12 months. The secondary endpoints are relapse time, response rate and side effects.

Official Title
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Efficacy of Mycophenolate Mofetil Versus Leflunomide as Maintenance Treatment for IgG4-RD Patients With Internal Organ Involvement

Conditions
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Autoimmune Diseases

Intervention / Treatment
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* Drug: Prednisone and Mycophenolate Mofetil
* Drug: Mycophenolate Mofetil
* Drug: Leflunomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Fulfillment of the 2019 American College of Rheumatology/European League against Rheumatology (ACR/EULAR) IgG4-related disease classification criteria; 2. Newly-onset or relapsed patients who requires initiation or continuation of glucocorticoids treatment; 3. The addition of glucocorticoids was started at lower than 10 mg/d. Exclusion Criteria: 1. Patients who were diagnosed as other autoimmune diseases; 2. Patients who were diagnosed as malignant diseases; 3. Pregnant and lactating women； 4. Active infection: HIV, HCV, HBV, TB； 5. Severe irreversible damage of organ function; 6. Receipt of any biologic therapy or immunosuppressive agent other than GCs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Group I<br>Patients are treated with glucocorticoids and mycophenolate mofetil in remission induction period (6 months), during which glucocorticoids are tapered regularly and discontinued in 4 months. Afterwards, patients are treated with low dose mycophenolate (0.5-1g/day) during remission maintenance period for 9 months. | Drug: Prednisone and Mycophenolate Mofetil<br>* Patients are treated with glucocorticoids and mycophenolate mofetil in remission induction period (6 months), during which glucocorticoids are tapered regularly and discontinued in 4 months.<br>Drug: Mycophenolate Mofetil<br>* Patients are treated with low dose mycophenolate (0.5-1g/day) during remission maintenance period for 9 months.<br>|
| Experimental: Group II<br>Patients are treated with glucocorticoids and mycophenolate mofetil in remission induction period (6 months), during which glucocorticoids are tapered regularly and discontinued in 4 months. Afterwards, patients are treated with leflunomide (10-20 mg/day) during remission maintenance period for 9 months. | Drug: Prednisone and Mycophenolate Mofetil<br>* Patients are treated with glucocorticoids and mycophenolate mofetil in remission induction period (6 months), during which glucocorticoids are tapered regularly and discontinued in 4 months.<br>Drug: Leflunomide<br>* Patients are treated with leflunomide (10-20 mg/day) during remission maintenance period for 9 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of relapse rate of IgG4-RD between two groups in 12 months. | The definition of relapse: elevation of IgG4-RD Responder Index ≥ 2 points; new organ involvement or recurrence, with or without elevation of serum IgG4 levels. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of the time at baseline to first relapse between two groups. |  | 12 months | 
| Response rate to the treatment of the two groups. | Complete response rate; Partial response rate; No response | 12 months | 
| Side effects | Any side effects caused by treatments for IgG4-RD. | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulin G4-Related Disease, treatment strategies, relapse, leflunomide, mycophenolate mofetil