This study has been designed as a 52-week, randomized double blind placebo controlled multicenter clinical trial. The study aims to compare the efficacy and safety of two treatment strategies in IgG4-RD patients with re-elevation of serum IgG4 level during maintenance remission period: basic maintenance treatment group (continue use of basic maintenance treatment of IgG4-RD) and enhanced treatment group (use low dose mycophenolate mofetil as an add-on therapy of basic maintenance treatment of IgG4-RD).

108 IgG4-RD patients with re-elevation of serum IgG4 level to ≥30% of baseline serum IgG4 level during maintenance remission period are to be enrolled in this study after screening period, and then double blind randomly in an 1:1 ratio into two groups: basic maintenance treatment group (continue use of basic maintenance treatment of IgG4-RD plus placebo) and enhanced treatment group (use low dose mycophenolate mofetil as an add-on therapy of basic maintenance treatment of IgG4-RD). The follow-up period will be 52 weeks. During the follow-up period, clinical evaluations, laboratory tests, image examinations and IgG4-RD responder index (RI) will be recorded. The primary endpoint is the difference of relapse rate between two groups at 52 weeks. Meanwhile, this study will also explore and study different biomarkers in IgG4-RD patients, to better understand the mechanisms, as well as prognostic factors of IgG4-RD.

Inclusion Criteria:

• 1. Fulfillment of the 2019 American College of Rheumatology/European League against Rheumatology (ACR/EULAR) IgG4-related disease classification criteria or the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.
• 2. Age between 18 and 70 years.
• 3. Elevation of baseline serum IgG4 level (>1400mg/L).
• 4. Major organ involvement, including but not limited to autoimmune pancreatitis, retroperitoneal fibrosis, sclerosing cholangitis, IgG4-related Castleman disease, and involvement of the lungs, kidney, nasal sinus, and central nervous system.
• 5. Re-elevation of serum IgG4 level to ≥30% of baseline serum IgG4 level during maintenance remission period, with no evidence of relapse.
• 6. Written informed consent signed.
• 7. Agreed to take highly effective contraceptive procedures from signing of informed consent till 6 months after the end of last visit.

Exclusion Criteria:

• 1. Patients with an IgG4-RD Responder Index ≥ 2 points of any organ system.

• 2. IgG4-RD patients without major organ involvement.

• 3. Patients with severe or active infections, including but not limited to HIV, HCV, HBV, TB.

• 4. Patients with malignancies or a history of malignancies within 5 years, except:

  1. Patients with adenocarcinoma in situ (AIS) of the cervix who have received curative treatment for at least 12 months before screening.
  2. Patients with cutaneous basal or squamous cell carcinoma who have received curative treatment.
  3. Patients with prostate cancer, who have received radical prostatectomy or definitive radiotherapy for over 3 years, with no sign of relapse or ongoing treatment

• 5. Patients with immunodeficiency diseases.

• 6. Patients with severe cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neuropsychological, or constitutional comorbidities; or at risk of unacceptable complications, or having confounding factors in safety and explanation of results according to the evaluations from investigators.

• 7. Patients with other rheumatic diseases, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, sarcoidosis; or other mimickers of IgG4-RD, including but not limited to Rosai-Dorfman disease, Castleman disease.

• 8. Participating in any other clinical trials with drug interventions.

• 9. A history of alcohol or drug abuse, possibly harming patient's safety, compliance, or evaluation of study's safety or other necessary aspects according to the evaluations from investigators.

• 10. Women during pregnancy, lactation, or planning of pregnancy within 6 months of the last visit of the study.

• 11. Meeting any of the following blood test finding on screening:

  1. Hemoglobin level < 7.5g/dL.
  2. neutrophil count < 1.0×10^9/L.
  3. Platelet count < 100×10^9/L.
  4. Alanine aminotransferase (ALT) > 2 × upper limit number (ULN).
  5. Aspartate aminotransferase (AST) > 2 × ULN.
  6. Total Bilirubin (TBil) > 2 × ULN.
  7. Estimated glomerular filtration rate (eGFR) < 30ml/(min·1.73m^2), calculated using the Modification of Diet in Renal Disease (MDRD) study equation by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).