Development of an IgG4-RD Responder Index

IgG4-related disease (IgG4-RD) is a multiorgan inflammatory disease in which diverse organ manifestations are linked by common histopathological and immunohistochemical features. Prospective studies of IgG4-RD patients are required to clarify the natural history, long-term prognosis, and treatment approaches in this recently recognized condition. Patients with IgG4-RD have different organ manifestations and are followed by multiple specialties. Divergent approaches to the assessment of patients can complicate the interpretation of studies, emphasizing the critical need for validated outcome measures, particularly assessments of disease activity and response to treatment. We developed a prototype IgG4-RD Responder Index (IgG4-RD RI) based on the approach used in the development of the Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG). The IgG4-RD RI was refined by members of the International IgG4-RD Symposium Organizing Committee in a paper case exercise. The revised instrument was applied retrospectively to fifteen IgG4-RD patients at our institution. Those scores were compared to physician’s global assessment scale for the same visits. This paper describes the philosophy and goals of the IgG4-RD RI, the steps in the development of this instrument to date, and future plans for validation of this instrument as an outcome measure. 1. Introduction Measurement of disease activity is critical for longitudinal assessments in both observational studies and clinical trials. In the field of rheumatology, more than 250 assessment tools have been developed and validated to evaluate pathology, symptoms, function, and health status of patients with rheumatic diseases [1]. Such instruments should be compatible with regulatory requirements of the Food and Drug Administration (FDA) and generally require prospective studies for completion of the validation process [2]. IgG4-related disease (IgG4-RD) is an increasingly recognized immune-mediated disease that is characterized by a lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells and a distinctive storiform fibrosis of affected organs [3]. Commonly involved organs include the pancreas, biliary tree, orbits, salivary glands, and retroperitoneum, among many others. Organ involvement usually occurs in a metachronous but overlapping fashion. The serum IgG4 level is often but not always elevated [4]. Because of the novelty of IgG4-RD, little effort to date has been devoted to the development of outcome measures for this newly recognized condition. A disease responder index is a