Withdraw Drug in Stable IgG4-Related Disease

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

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

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: Drug free, IS monotherapy and GC combined with IS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 138
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: linyi peng, MD.; Phone Number: +8615810395901; Email: drpenglinyi@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital
      • Contact: Yanying Liu, MD; Phone Number: 13581746850; Email: liuyanying20030801@msn.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Disease stabilized more than one year (Responder Index < 2 points)
3. Dose of Glucocorticoid(GC): prednisone (or equivalent) ≤ 7.5mg/d for more than 6 months
4. 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:

1. Patient was diagnosed other connective tissue diseases
2. Patient with tumor
3. Women during pregnancy or planning pregnancy
4. Patient with active infections, including HIV, HCV, HBV, TB, etc.
5. Patient with severe irreversible organ damage
6. Active IgG4-RD, responder index >= 2 points
7. Stable condition less than one year.
8. Patient with two or more immunosuppressive agents.
9. Biological agents (such as CD20 monoclonal antibody and TNF-a inhibitor) have been used for half a year before admission.
10. Patient with IgG4-RD recurrence during hormone reduction in the past.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug free; 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; Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).
EXPERIMENTAL: IS monotherapy; 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; Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).
EXPERIMENTAL: GC combined with IS; 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; Follow-up intervals: Every 3 months (3th, 6th, 9th, 12th, 15th, 18th month).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University People's Hospital; Chinese PLA General Hospital; Tongji Hospital; Shengjing Hospital; The People's Hospital of Hebei Province
• Investigators: Principal Investigator: Wen Zhang, MD., Peking Union Medical College Hospital; Study Director: Yunyun Fei, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 23, 2020
• Primary Completion (ANTICIPATED): December 30, 2022
• Study Completion (ANTICIPATED): June 30, 2023

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (ACTUAL): October 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Immunoglobulin G4-Related Disease
• Additional Relevant MeSH Terms: Immune System Diseases; Immunoglobulin G4-Related Disease; Autoimmune Diseases
• Other Study ID Numbers: Withdraw drug in IgG4-RD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No