Evaluating the Safety and Efficacy of Rituxmab for IgG4-Related Disease

San Diego—Preliminary results of a prospective, open-label, pilot trial showed that rituximab may be a safe and effective treatment option for patients with immunoglobulin G4-related disease (IgG4-RD), a multi-organ, fibro-inflammatory disorder, according to study results presented at the ACR/ARHP meeting.

Although most patients with IgG4-related disease respond to steroids, they do not cure the disease and few patients are able to discontinue steroids completely. Data show that only 63% of patients achieve complete remission, and most will have a disease flare at some point. Data indicating the efficacy of traditional steroid-sparing medications does not currently exist.

Investigators from Massachusetts General Hospital and Mayo Clinic conducted an open-label, 2-center, prospective trial to examine the efficacy of rituximab in 30 patients during a 6-month period.

The study specifically examined minimizing steroid use and measuring the efficacy of rituximab alone when possible. Three measures were used for the primary outcome: (1) disease response (decrease of responder index of >2 points from baseline); (2) no disease flares before 6 months; and (3) no use of glucocorticoids between months 2 and 6 of the study period. Patients who achieved disease activity score of 0 were considered to be in complete remission.

The patients in the study had histopathologically-proven diagnosis of IgG4-RD, at least 2 out of the 3 major features (ie, lymphoplasmacytic infiltrate, storiform fibrosis, as well as obliterative phlebitis and immunoperoxidase staining >10 IgG4+ plasma cells per HPF and a >40% IgG4/IgG ratio), and had active disease based on the IgGr-RD responder index (IgG4-RD RI).

All patients were treated with rituximab 1000 mg with 2 doses on days 0 and 15 as well as methylprednisolone 100 mg with each rituximab dose. No patients received maintenance rituximab.

Overall, most patients in the study were men (87%) and a mean age of 63 years (range, 42-82 years). At baseline, the mean IgG4-RD RI was 12.7 (range, 5-36), and the mean IgG4-RD concentration was 534 mg/dL (normal <121; range, 22-4780 mg/dL). Among patients in the trial, the organ system involved included the entire spectrum of IgG4-RD (eg, biliary tree, hypopharynx, kidney, lungs, lymph nodes, orbits, pancreas, pericardium, prostate, orbits, retroperitoneum, salivary glands).

Overall, steroid-free disease responses were achieved in 26 patients (93%) followed for at least 1 month and 22 of 24 patients (92%) followed for 3 months. Of the 23 patients who completed 6 months of rituximab, 20 (87%) achieved the primary outcome.

After the first month, only 2 of 28 patients needed an increased dose of prednisone. John Stone, MD, MPH, director, clinical rheumatology, Massachusetts General Hospital, Boston, Massachusetts, said the results suggest rituximab may be a highly effective treatment for patients with IgG4-RD, and may play an important role for patients in with IgG4-RD refractory disease and in patients where steroids are contraindicated.