Withdraw Drug in Stable IgG4-Related Disease

Not Applicable

• Conditions: Autoimmune Diseases
• Interventions: Drug: Drug free, IS monotherapy and GC combined with IS

• Registration Number: NCT04124861
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-02-13
• Study First Submitted QC: 2019-10-10
• Study First Posted: 2019-10-11
• Study Start: 2020-06-23
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-21
• Last Update Posted: 2022-02-07
• Primary Completion: 2022-12-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 138

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IS monotherapy	Drug free, IS monotherapy and GC combined with IS	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)
GC combined with IS	Drug free, IS monotherapy and 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 free	Drug free, IS monotherapy and GC combined with IS	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.

Primary Outcome Measures

Name	Time	Method
The difference of recurrent rate of IgG4-RD among three groups.	One and half year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beijing Friendship Hospital; 🇨🇳 Beijing, Beijing, China