title: Predictors of disease relapse in IgG4-related disease following rituximab.
abstract: 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.
  
  
  CONCLUSIONS
  Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently.
authors.affiliation: Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Wallace
authors.affiliation: Massachusetts General Hospital Cancer Center, The Ragon Institute of the Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mattoo
authors.affiliation: Massachusetts General Hospital Cancer Center, The Ragon Institute of the Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University.
authors.forename: Vinay S
authors.initials: VS
authors.lastname: Mahajan
authors.affiliation: Massachusetts General Hospital Cancer Center, The Ragon Institute of the Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University.
authors.forename: Maria
authors.initials: M
authors.lastname: Kulikova
authors.affiliation: Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Boston University School of Medicine.
authors.forename: Leo
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Hyon K
authors.initials: HK
authors.lastname: Choi
authors.affiliation: Massachusetts General Hospital Cancer Center, The Ragon Institute of the Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University, Harvard Medical School, Boston, MA, USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA jhstone@mgh.harvard.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007073:Immunoglobulin E; D000069283:Rituximab
keywords: IgE; IgG4; IgG4-related disease; IgG4RD Responder Index; biomarker; eosinophil; relapse; remission; rituximab