Predictors of disease relapse in IgG4-related disease following rituximab

Rheumatology (Oxford). 2016 Jun;55(6):1000-8. doi: 10.1093/rheumatology/kev438. Epub 2016 Feb 16.


Objective: IgG4-related disease (IgG4-RD) is a relapsing-remitting condition responsible for fibroinflammatory lesions that can lead to organ damage and life-threatening complications at nearly any anatomical site. The duration of remission following treatment varies and predictors of relapse are unclear. The objectives of this study were to review our experience with rituximab as remission induction in IgG4-RD, to clarify the duration of efficacy and to identify predictors of flare following treatment.

Methods: In this retrospective cohort study, all patients were treated with two doses of rituximab (1 g) separated by 15 days. Clinical, radiographic and laboratory data pertaining to rituximab response and disease relapse were collected from the electronic medical record. Kaplan-Meier curves were constructed to estimate the time to disease relapse. Log-rank analyses were performed to compare times to relapse among subgroups. Potential relapse predictors were evaluated with Cox regression analysis.

Results: Fifty-seven of 60 patients (95%) had clinical responses to rituximab. Forty-one patients (68%) were treated without glucocorticoids. Twenty-one patients (37%) experienced relapses following treatment at a median time from the first infusion of 244 days. Baseline concentrations of serum IgG4, IgE and circulating eosinophils predicted subsequent relapses, with hazard ratios of 6.2 (95% CI: 1.2, 32.0), 8.2 (95% CI: 1.4, 50.0) and 7.9 (95% CI: 1.8, 34.7), respectively. The higher the baseline values, the greater the risk of relapse and the shorter the time to relapse. Only 10% of the patients had elevations of all three major risk factors, underscoring the importance of measuring all three at baseline.

Conclusion: Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently.

Keywords: IgE; IgG4; IgG4-related disease; IgG4RD Responder Index; biomarker; eosinophil; relapse; remission; rituximab.

MeSH terms

  • Adult
  • Aged
  • Autoimmune Diseases / blood*
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Biomarkers / blood
  • Eosinophils / metabolism
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Immunologic Factors / administration & dosage*
  • Kaplan-Meier Estimate
  • Leukocyte Count
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Recurrence
  • Remission Induction / methods
  • Retrospective Studies
  • Risk Factors
  • Rituximab / administration & dosage*
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Immunoglobulin G
  • Immunologic Factors
  • Immunoglobulin E
  • Rituximab