Zachary S Wallace1, Hamid Mattoo2, Vinay S Mahajan2, Maria Kulikova2, Leo Lu3, Vikram Deshpande4, Hyon K Choi5, Shiv Pillai6, John H Stone7. 1. Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital. 2. Massachusetts General Hospital Cancer Center, The Ragon Institute of the Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University. 3. Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Boston University School of Medicine. 4. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 5. Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 6. 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. 7. Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA jhstone@mgh.harvard.edu.
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. CONCLUSION: Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently.
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.
Authors: Mollie N Carruthers; Arezou Khosroshahi; Tamara Augustin; Vikram Deshpande; John H Stone Journal: Ann Rheum Dis Date: 2014-03-20 Impact factor: 19.103
Authors: Vikram Deshpande; Yoh Zen; John Kc Chan; Eunhee E Yi; Yasuharu Sato; Tadashi Yoshino; Günter Klöppel; J Godfrey Heathcote; Arezou Khosroshahi; Judith A Ferry; Rob C Aalberse; Donald B Bloch; William R Brugge; Adrian C Bateman; Mollie N Carruthers; Suresh T Chari; Wah Cheuk; Lynn D Cornell; Carlos Fernandez-Del Castillo; David G Forcione; Daniel L Hamilos; Terumi Kamisawa; Satomi Kasashima; Shigeyuki Kawa; Mitsuhiro Kawano; Gregory Y Lauwers; Yasufumi Masaki; Yasuni Nakanuma; Kenji Notohara; Kazuichi Okazaki; Ji Kon Ryu; Takako Saeki; Dushyant V Sahani; Thomas C Smyrk; James R Stone; Masayuki Takahira; George J Webster; Motohisa Yamamoto; Giuseppe Zamboni; Hisanori Umehara; John H Stone Journal: Mod Pathol Date: 2012-05-18 Impact factor: 7.842
Authors: Arezou Khosroshahi; Lynn A Cheryk; Mollie N Carruthers; Judith A Edwards; Donald B Bloch; John H Stone Journal: Arthritis Rheumatol Date: 2014-01 Impact factor: 10.995
Authors: Phil A Hart; Terumi Kamisawa; William R Brugge; Jae Bock Chung; Emma L Culver; László Czakó; Luca Frulloni; Vay Liang W Go; Thomas M Gress; Myung-Hwan Kim; Shigeyuki Kawa; Kyu Taek Lee; Markus M Lerch; Wei-Chih Liao; Matthias Löhr; Kazuichi Okazaki; Ji Kon Ryu; Nicolas Schleinitz; Kyoko Shimizu; Tooru Shimosegawa; Roy Soetikno; George Webster; Dhiraj Yadav; Yoh Zen; Suresh T Chari Journal: Gut Date: 2012-12-11 Impact factor: 23.059
Authors: Hyon K Choi; John H Stone; Zachary S Wallace; Yuqing Zhang; Cory A Perugino; Ray Naden Journal: Ann Rheum Dis Date: 2019-01-05 Impact factor: 19.103
Authors: Mark A Matza; Cory A Perugino; Liam Harvey; Ana D Fernandes; Zachary S Wallace; Hang Liu; Hugues Allard-Chamard; Shiv Pillai; John H Stone Journal: Lancet Rheumatol Date: 2021-12-01
Authors: Zachary S Wallace; Arezou Khosroshahi; Mollie D Carruthers; Cory A Perugino; Hyon Choi; Corrado Campochiaro; Emma L Culver; Frank Cortazar; Emanuel Della-Torre; Mikael Ebbo; Ana Fernandes; Luca Frulloni; Phil A Hart; Omer Karadag; Shigeyuki Kawa; Mitsuhiro Kawano; Myung-Hwan Kim; Marco Lanzillotta; Shoko Matsui; Kazuichi Okazaki; Jay H Ryu; Takako Saeki; Nicolas Schleinitz; Paula Tanasa; Hisanori Umehara; George Webster; Wen Zhang; John H Stone Journal: Arthritis Care Res (Hoboken) Date: 2018-11 Impact factor: 4.794