Background/Purpose:
IgG4-related disease (IgG4-RD) is a multi-organ, fibro-inflammatory disorder. An open label pilot trial of rituximab (RTX) in IgG4-RD conducted at twocentershas enrolled 29 of the targeted 30 patients. We report preliminary results on28 patientsfollowed for a minimum of one month.
Methods:
The trial was approved by institutional review boards at the Massachusetts General Hospital and Mayo Clinic. All patients had histopathologically-proven diagnoses of IgG4-RD, includingat least two out of the three major featuresoflymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis AND immunoperoxidase staining >10 IgG4+ plasma cells per HPF and a >40% IgG4/IgG ratio.All patients had active disease, based on the IgG4-RD Responder Index (IgG4-RD RI). Patients were treated with RTX(1000 mg) times two doses (days 0 and 15) but not treated with maintenance RTX. Patients received methylprednisolone 100 mg with each RTX dose. Trial visits were performed at 1, 3, 5, 6, 8, 10, and 12 months after the first rituximab infusion. The primary outcome was defined by three measures: 1) disease response (decrease of responder index of ≥2 points from baseline); 2) no disease flares before month 6; and, 3) no glucocorticoids between months 2 and 6. Complete remission was defined as an IgG4-RD RI disease activity score of zero.
Results:
The organ system involvement among patients in the trial spanned the full spectrum of IgG4-RD, including the orbits, salivary glands, hypopharynx, lungs, lymph nodes, pericardium, pancreas, biliary tree, retroperitoneum, kidney, prostate, and others. The mean IgG4-RD RI at baseline was 12.7 (range: 5 – 36).The mean serum IgG4 concentration was 534 mg/dL (normal < 121; range: 22 – 4780), but 12 patients (43%) had normal values at baseline. Prednisone was used concomitantly with RTX at baseline for remission induction in only 2 of the 28 patients. Twenty-six of the 28 patients followed for at least one month and 22 of 24 followed for three months achieved steroid-free achieved disease responses (93% and 92% at these two timepoints, respectively). Among the 23 patients completing six months of follow-up to date, 20 (87%) have achieved the primary outcome. Only 2 of the 28 patients required an increase in prednisone dose after Month 1. Two patients were hospitalized during the study, one for Legionnaire’s disease (pre-baseline infection) and the other for a cold agglutinin-mediated autoimmune hemolytic anemia. No serious adverse events related to rituximab were reported.
Conclusion:
Rituximab has promise as a safe, effective treatment for IgG4-RD.Excellent disease responses have been observed to date despite the absence of concomitant glucocorticoid use in this trial.
Disclosure:
M. Carruthers,
None;
M. Topazian,
None;
A. Khosroshahi,
None;
T. Witzig,
None;
J. Oakley,
None;
P. Hart,
None;
L. Kelly,
None;
L. Bergstrom,
None;
S. Chari,
None;
J. Stone,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rituximab-for-the-treatment-of-igg4-related-disease-a-prospective-clinical-trial/