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Variability in the biological response to anti-CD20 B-cell depletion in SLE
  1. Daniel Albert (daniel.a.albert{at}hitchcock.org)
  1. Dartmouth Medical School, United States
    1. Jonathan Dunham (jonathan.dunham{at}uphs.upenn.edu)
    1. University of Pennsylvania, United States
      1. Sadia Khan
      1. University of Pennsylvania, United States
        1. Janet Stansberry
        1. University of Pennsylvania, United States
          1. Sharon Kolasinski
          1. University of Pennsylvania, United States
            1. Donald Tsai
            1. University of Pennsylvania, United States
              1. Sally Pullman-Mooar
              1. University of Pennsylvania, United States
                1. Felicia Barnack
                1. University of Pennsylvania, United States
                  1. Christopher Striebich
                  1. University of Colorado, United States
                    1. R John Looney
                    1. Unviversity of Rochester, United States
                      1. Eline T Luning Prak
                      1. University of Pennsylvania, United States
                        1. Robert Kimberly
                        1. University of Alabama at Birmingham, United States
                          1. Yawei Zhang
                          1. University of Pennsylvania, United States
                            1. Robert Eisenberg (raemd{at}mail.med.upenn.edu)
                            1. University of Pennsylvania, United States

                              Abstract

                              Objective: To study the effects in systemic lupus erythematosus (SLE) of B-cell directed therapy with rituximab, a chimeric monoclonal antibody directed at CD20+ B cells, without concomitant immunosuppressive therapy in mild to moderate SLE.

                              Methods: Patients (n=24) with active SLE and failure of ≥1 immunosuppressive were recruited from three university centers into this Phase I/II prospective open-label study. Patients were followed for one year to assess safety, efficacy, and biologic effects.

                              Results: Eighteen of the patients scheduled to receive the full lymphoma dose of rituximab were evaluable for B-cell levels in peripheral blood. Of these, 17 had effective CD19+ B-cell depletion (<5 per μL). However, 6 of the depleted patients showed B-cell return before 24 weeks. Seventy percent of patients improved by Week 55, as defined by an SLE Disease Activity Index (SLEDAI) score improvement of ≥2 units from baseline. The degree of CD19+ B-cell depletion was correlated with SLEDAI improvement at Week 15 (r=0•84). In general, rituximab infusions were well tolerated. Approximately one-third of the patients developed human anti-chimeric antibody (HACA) titers, which correlated with poor B-cell depletion. Most patients (9 of 14) did not respond to immunizations with Pneumovax and tetanus toxoid.

                              Conclusions: Rituximab is a promising new therapy for SLE. The variability of responses in SLE patients may be related to HACA formation. The failure to respond to immunizations is surprising, in view of the apparently low risk of infections. Better biologic markers are necessary to follow these patients during treatment.

                              • B cells
                              • CD20
                              • SLE
                              • rituximab

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