Six Refractory Lupus Patients Treated With Rituximab: A Case Series JOANN ZELL GILLIS, MARIA DALL’ERA, ANDREW GROSS, JINOOS YAZDANY, AND JOHN DAVIS Introduction Systemic lupus erythematosus (SLE) is characterized by the loss of B cell tolerance with resultant autoantibody production directed toward self antigen. The pathogenic properties of autoantibodies in patients with SLE include direct cell-mediated destruction, interruption of normal cellular processes, and the formation of immune com- plexes that activate complement. For years, most research efforts in SLE focused on the T cell–triggering arm of the inflammatory response. However, recent interest has shifted to explore the potential pathogenic role of the B cell. B cell– directed therapy with rituximab, initially used for the treatment of non-Hodgkin’s lymphoma (1), has been reported to be effective in the treatment of several autoimmune conditions such as rheumatoid arthritis, sys- temic vasculitis, Sjo ¨ gren’s syndrome, and autoimmune thrombocytopenia (2– 4). Initially, rituximab was thought to treat autoimmune conditions by limiting the production of autoantibodies; however, the precise mechanism is un- clear. In fact, some open-label clinical studies show mod- est to little effect on circulating autoantibodies and quan- titative immunoglobulin (5–7). In lymphoma, rituximab causes rapid depletion of CD20+ cells in the peripheral blood, often within weeks of initial infusion. However, duration of B cell suppression is variable, lasting 2–12 months on average (1). There have been reports of several open-label studies of rituximab in patients with SLE (2,5– 8). Indications range from inability to tolerate other medications to intractable disease. These trials demonstrate improvement in most domains of SLE, including renal and central nervous sys- tem disease. Rituximab dosing has shown great variability with regard to 1) actual drug dose, 2) scheduling, and 3) concomitant or conditioning regimens. At this time, it remains unclear which dosing schema offers the safest and most efficacious profile. In this report, we describe 6 pa- tients with aggressive and refractory SLE treated with rit- uximab and illustrate how rituximab can be safely admin- istered to patients with several dosing regimens. Patients and Methods Patients were seen at the University of California San Francisco Lupus Clinic, an academic practice. Patients received rituximab if they either demonstrated significant disease activity despite available therapies or were unable to tolerate therapeutic alternatives. Risks of using an off- label medication were thoroughly explained to all pa- tients. All of the patients included in this series met 4 of the American College of Rheumatology revised classifica- tion criteria for SLE (9). Although dosing schedule differed in our series, all pa- tients were pretreated with acetaminophen, diphenhydra- mine, and steroids (either oral or intravenous [IV]). For each patient, a baseline physical examination and basic SLE laboratory tests were performed, and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (10) was administered. Each patient was evaluated at 2- month intervals for a total of at least 6 months (range 8 –21 months). Samples were obtained from patients at each visit to assess CD19+ lymphocyte levels, SLE serologies, creatinine level, complete blood count, liver function, qualitative immunoglobulin, and urinalysis. Statistical ana- lysis was performed by fitting linear mixed-effects models with random slopes and intercepts (11). These models assessed patient-to-patient variation by measuring the magnitude of both change over time and average response. STATA software, version 8.0 was used for analysis (Stata- Corp, College Station, TX). Results Clinical outcome. Patients were followed for a mini- mum of 6 months. Five of the 6 patients showed improve- Supported by the Lupus Clinical Trials Consortium, the State of California Lupus Funds, and the Rosalind Russell Medical Center for Arthritis. JoAnn Zell Gillis, MD, Maria Dall’Era, MD, Andrew Gross, MD, Jinoos Yazdany, MD, John Davis, MD, MPH: University of California, San Francisco. Dr. Davis serves as a primary investigator and Dr. Dall’Era serves as a co-investigator for 2 lupus studies with rituximab at the University of California San Francisco. Address correspondence to John Davis, MD, MPH, Asso- ciate Professor of Medicine, Division of Rheumatology, Uni- versity of California San Francisco, 533 Parnassus Avenue, Room U383, Box 0633, San Francisco, CA 94143. E-mail: jdavis@medicine.ucsf.edu. Submitted for publication January 5, 2006; accepted in revised form August 8, 2006. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 57, No. 3, April 15, 2007, pp 538 –542 DOI 10.1002/art.22629 © 2007, American College of Rheumatology TRAINEE ROUNDS 538