An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index

Zachary Wallace¹, Arezou Khosroshahi², Mollie Carruthers³, Campochiaro Corrado⁴, Hyon K. Choi⁵, Emma Culver⁶, Frank Cortazar⁷, Mikael Ebbo⁸, Ana Fernandes⁹, Luca Frulloni¹⁰, Omer Karadag¹¹, Shigeyuki Kawa¹², Mitsuhiro Kawano¹³, MH Kim¹⁴, Marco Lanzillotta¹⁵, Shoko Matsui¹⁶, Cory Perugino¹⁷, Kazuichi Okazaki¹⁸, Philip Hart¹⁹, Jay H. Ryu²⁰, Takako Saeki²¹, Nicolas Schleinitz²², Paula Tanasa²³, Hisanori Umehara²⁴, George Webster²⁵, Wen Zhang²⁶ and John H. Stone²⁷, ¹Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, ²Medicine, Emory University School of Medicine, Atlanta, GA, ³Rheumatology, University of British Columbia, Vancouver, BC, Canada, ⁴San Raffaele Scientific Institute, Milan, Italy, ⁵Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ⁶Translational Gastroenterology Unit and NDM Oxford University, Translational Gastroenterology Unit and NDM Oxford University, John Radcliffe Hospital/Oxford University, Oxford, United Kingdom, ⁷Department of Nephrology, Massachusetts General Hospital, Boston, MA, ⁸Internal Medicine, Aix-Marseille Université, AP-HM, Marseille, France, ⁹Rheumatology Unit, Massachusetts General Hospital, Boston, MA, ¹⁰Gastroenterology, University of Verona, Verona, Italy, ¹¹Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey, ¹²Center for Health, Safety and Environmental Management, Shinshu University, Matsumoto, Japan, ¹³Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan, ¹⁴University of Ulsan College of Medicine, Seoul, Korea, The Republic of, ¹⁵Vita-Salute San Raffaele University, Milan, Italy, ¹⁶University of Toyama, Toyama, Japan, ¹⁷Rheumatology, Massachusetts General Hospital, Boston, MA, ¹⁸Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan, ¹⁹Ohio State University Wexner Medical Center, Columbus, OH, ²⁰Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, ²¹Nagaoka Red Cross Hospital, Niigata, Japan, ²²La Timone University Hospital, Marseille, France, ²³Rheumatology, Emory University, Atlanta, GA, ²⁴Kyoto University, Kyoto, Japan, ²⁵University College Hospital, London, United Kingdom, ²⁶Rheuamtology, Peking Union Medical College Hospital, Beijing, China, ²⁷Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston, MA

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Disease Activity, IgG4 Related Disease and treatment

Session Information

Date: Sunday, November 13, 2016

Title: Miscellaneous Rheumatic and Inflammatory Diseases I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: IgG4-related disease (IgG4-RD) is an immune-mediated condition responsible for fibro-inflammatory lesions that can affect nearly any organ and lead to irreversible damage. To evaluate the efficacy of treatments, a tool understood and adopted by many types of specialists that can assess disease activity accurately and reliably across various organs is necessary. The IgG4-RD Responder Index (RI) was developed for this purpose. We sought to validate the RI among an international, multi-specialty group of IgG4-RD experts.

Methods: The RI requires participants to assess disease activity in 25 domains (24 disease sites and 1 domain for constitutional symptoms). Completing the instrument takes approximately three minutes per patient visit. Scoring incorporates higher weights for “urgent” manifestations and those that worsened despite treatment. After completing a training exercise, 25 participants were asked to review 12 written cases describing patients with diverse manifestations of IgG4-RD. The vignettes were supplemented by photographs, radiology images, and pictures of pathology findings. For each case, participants calculated the RI as well as a physician global assessment (PGA) of disease activity on a 100mm scale. We then assessed: 1) consistency (the inter-observer reliability) of the RI and PGA using intra-class correlation coefficients (ICCs); 2) precision (the inter-observer variation) by applying the signed rank test to the differences between the coefficients of variation for the RI and PGA of each case; 3) construct validity by determining the correlation between the RI and the PGA using the Spearman’s rank correlation coefficient; 4) and sensitivity to change (discriminant validity) using a paired T-test comparing RI scores before and after treatment in six consecutive real-life cases as well as by assessing the Spearman’s rank correlation coefficient when comparing the change in RI and PGA before and after treatment.

Results: Twenty five participants completed the study, including 11 rheumatologists, 5 gastroenterologists, 4 immunologists, 2 pulmonologists, 2 nephrologists, and 1 internist. Experts from the Canada, China, Italy, France, Japan, South Korea, Turkey, the UK, and the US participated. Correlations (construct validity) between the RI and PGA were high (r=0.9, P<0.0001). The consistency (interobserver reliability) was higher for the RI (r=0.88) than the PGA (r=0.83) as assessed using ICCs. The precision (interobserver variation) of the RI and PGA was similar (P=1). The RI was sensitive to change (discriminant validity). Following treatment (median 46.5 days, IQR 38-54 days), there was a significant improvement in the RI (P=0.007) and a high correlation between the change in RI and PGA (r=0.8, P=0.04).

Conclusion: In this international, multi-specialty study, we found that the RI is a valid and reliable disease activity assessment tool for IgG4-RD. The performance of the RI was assessed in patients with diverse manifestations of IgG4-RD in both cross-sectional and longitudinal phases. The RI can be used to determine the response to treatment and will be an important tool for international studies investigating the effectiveness of IgG4-RD treatment.

Disclosure: Z. Wallace, None; A. Khosroshahi, None; M. Carruthers, None; C. Corrado, None; H. K. Choi, None; E. Culver, None; F. Cortazar, None; M. Ebbo, None; A. Fernandes, None; L. Frulloni, None; O. Karadag, Pfizer Inc, 2,Abbvie, 2,Abbvie, 5,BMS, 5,MSD, 5,Pfizer Inc, 5,Roche Pharmaceuticals, 5,UCB, 5,Sanofi-Aventis Pharmaceutical, 5; S. Kawa, None; M. Kawano, None; M. Kim, None; M. Lanzillotta, None; S. Matsui, None; C. Perugino, None; K. Okazaki, None; P. Hart, None; J. H. Ryu, None; T. Saeki, None; N. Schleinitz, None; P. Tanasa, None; H. Umehara, None; G. Webster, None; W. Zhang, None; J. H. Stone, Genentech/Roche, 2,Xencor, 2,Xencor, 5,Genentech/Roche, 5.

To cite this abstract in AMA style:

Wallace Z, Khosroshahi A, Carruthers M, Corrado C, Choi HK, Culver E, Cortazar F, Ebbo M, Fernandes A, Frulloni L, Karadag O, Kawa S, Kawano M, Kim M, Lanzillotta M, Matsui S, Perugino C, Okazaki K, Hart P, Ryu JH, Saeki T, Schleinitz N, Tanasa P, Umehara H, Webster G, Zhang W, Stone JH. An International, Multi-Specialty Validation Study of the IgG4-Related Disease Responder Index [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/an-international-multi-specialty-validation-study-of-the-igg4-related-disease-responder-index/. Accessed .

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-international-multi-specialty-validation-study-of-the-igg4-related-disease-responder-index/