First Proof for Rituximab in IgG4-Related Disease

Alice Goodman

November 01, 2013

SAN DIEGO — Rituximab (Rituxan, Genentech) is a potential treatment option in the multiorgan fibroinflammatory disorder known as immunoglobulin G4-related disease (IgG4), according to researchers reporting first evidence.

"New therapeutic strategies are needed for IgG4," said lead investigator John Stone, MD, from Massachusetts General Hospital in Boston, who has worked on much of the research on this recently recognized disorder. "Glucocorticoids can be effective in many cases, but they do not cure the disease or lead to long-standing remissions in most cases."

IgG4 is known to comprise more than a dozen conditions formerly regarded as single-organ problems, explained Dr. Stone. It can mimic Sjogren's syndrome, granulomatosis with polyangitis, systemic lupus erythematosus, and sarcoidosis, as well as infections and malignancies.

Dr. Stone presented the results of the study during a plenary session here at the American College of Rheumatology 2013 Annual Meeting.

Treatment with rituximab makes sense, but this is the first time it has been studied.

The prospective open-label trial involved 28 patients with confirmed IgG4 disease affecting various areas, including the eyes, salivary glands, hypopharynx, lungs, lymph nodes, pericardium, pancreas, biliary tract, retroperitoneum, kidneys, and prostate. Most of the patients were male, with a median age of 63 years.

Patients received 2 doses of rituximab 1000 mg, 2 weeks apart, as well as methylprednisolone 100 mg with each rituximab treatment. The primary end point was disease response, measured by at least a 2-point decrease in IgG4 Responder Index and the ability to remain off steroids.

The majority of patients, 92%, achieved the primary end point and had no disease flares or steroids for 6 months.

Two patients required an increase in prednisone after month 1. Two patients were hospitalized, 1 for Legionnaire's disease that was present at baseline, and 1 for autoimmune hemolytic anemia. No serious unexpected adverse effects were attributed to rituximab.

New Biomarker

The investigators also looked at mechanistic parameters associated with IgG4, and identified elevated plasmablasts as a potential biomarker.

This is important, said Dr. Stone, because a proportion of patients will have normal serum concentrations of IgG4. The disease has been difficult to diagnose, and elevated plasmablasts might be a way to identify patients with the disorder and spare them from prolonged steroid treatment, he added.

"This disorder explains myriad previously undiagnosed patients," said Arthur Kavanaugh, MD, from the University of California, San Diego, who discussed this abstract at a highlights session. "IgG4 is the hippest diagnosis around. Look for it and you can find it."

He noted that "this study is a major advance. Treatment with rituximab makes sense, but this is the first time it has been studied. These data give us some support and we look forward to more."

Dr. Stone and Dr. Kavanaugh have disclosed no relevant financial relationships.

ACR 2013 Annual Meeting: Abstract 2649. Presented October 29, 2013.


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