Rituximab in IgG4-RD: A Phase 1-2 Trial

Inclusion Criteria: Patients will be included in the trial based on the following disease-specific criteria: * Age 18 or older * Diagnosis of IgG4-RD, based upon either pathological criteria\* (for those who have undergone biopsies) or clinical criteria.\*\* The criteria for pathological and clinical diagnoses are specified below. * The subject can be either steroid-naive, in relapse, steroid dependent, or refractory to steroids. Subjects who are steroid dependent or refractory are eligible for enrollment if steroid dose has not been increased in the past 2 weeks, and their treating physician plans to withdraw steroids completely (by dose taper) within 8 weeks of starting rituximab. * Pathological diagnosis: * Histopathologic features consisting of a lymphoplasmacytic infiltrate and storiform fibrosis within involved organs. Other histopathologic features consistent with IgG4-RD (e.g., obliterative phlebitis) may be present but are not required. * Either an IgG4/IgG plasma cell ratio of \> 50% within the affected organs or more than 10 IgG4-bearing plasma cells per high-power field. All patients with pathologic diagnoses will have their specimens reviewed by pathology investigators. \*\*Clinical diagnosis: • Organ involvement in a pattern consistent with IgG4-RD. This must include dysfunction of one of the following organs: pancreas (autoimmune pancreatitis); salivary glands (chronic sclerosing sialadenitis); lacrimal glands; orbital pseudotumor; kidneys; lungs; lymph nodes; meninges; aorta (including aortitis/periaortitis and/or retroperitoneal fibrosis); thyroid gland (Riedel's thyroiditis). If a patient is enrolled with a clinical diagnosis alone, the diagnosis must be accompanied by both an imaging finding compatible with IgG4-RD and a 1.5-fold elevation in the serum IgG4 concentration. Exclusion Criteria: Patients will be excluded from the study based on the following criteria: Disease-Specific Concerns: Excessive fibrosis within organs, such that a disease response to rituximab would not be expected. General Medical Concerns: * Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment), or lactating. * Inability to comply with study and/or follow-up procedures. Rituximab-Specific Concerns: * History of HIV. * Presence of active infection. * New York Heart Association Classification III or IV heart disease (See Appendix D). * Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. * At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization. * Positive hepatitis B or C serology is considered a potential exclusion criterion. Hepatitis B screening should include hepatitis B antibody and surface antigen for a patient with no risk factors. For patients with risk factors or previous history of hepatitis B, add core antibodies and e-antigen. * Allergies: History of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein. * Uncontrolled disease: They show evidence of other uncontrolled disease, including drug and alcohol abuse, which that could interfere with participation in the trial according to the protocol. * History of anti-human anti-chimeric antibody formation.