Presentation: Relapses in Rituximab-Treated Wegener’s Granulomatosis Patients Despite Peripheral B Cell Depletion (2007)

2020 Relapses in Rituximab-Treated Wegener’s Granulomatosis Patients Despite Peripheral B Cell Depletion

Purpose: Wegener’s granulomatosis (WG) is a chronic relapsing disorder, with significant disease- and treatment-related morbidity, emphasizing the need for safer, more effective therapies. Rituximab (RIT), an anti-CD20 monoclonal antibody that leads to B cell depletion, has demonstrated encouraging safety and efficacy in uncontrolled series of WG patients. A multicenter, randomized, controlled trial is currently underway investigating the efficacy and safety of RIT for the treatment of WG. We describe the occurrence of relapse in WG patients treated with open-label RIT.
Methods: Patients were included if they had a WG relapse despite depletion of circulating B cells following RIT treatment. Four such patients were identified by retrospective chart review. All 4 fulfilled the ACR classification criteria for WG. Disease activity was assessed by BVAS/WG.
Results: Median age was 36.5 years (range 23-57); three patients were female; all were Caucasian. Mean disease duration was 8 years (range 4-15); patients had previously been treated with a median of 3 immunosuppressive drugs in addition to prednisone (range 3-4). All were cANCA-PR3 positive at diagnosis; one was positive at the time of RIT treatment. Three patients were treated with 4 weekly RIT doses of 375mg/m2; and one with 2 doses of 1g, 2 weeks apart. All received concomitant intravenous methylprednisolone (≤500mg) with each RIT infusion, as well as oral prednisone. None received concomitant cyclophosphamide. One received RIT for immune-mediated thrombocytopenia concurrent with WG; this resolved with RIT treatment. The other 3 patients were treated with RIT for active WG, all of whom had a good initial response to RIT; median BVAS/WG prior to RIT was 4 (range 3-7); this had reduced to a median of 1 (range 1-4) 1 month after RIT. However, all 4 patients had a WG relapse at a median interval of 2 months (range 1.5-8 months) following initiation of RIT treatment. All 4 had peripheral B cell depletion at the time of relapse. Median BVAS/WG at the time of relapse was 4 (range 3-6). The items scored for each patient included 1. sinusitis, arthralgias and enlarging pulmonary nodules; 2. sinusitis, arthritis, conjunctivitis/lacrimal duct inflammation and new pulmonary nodules; 3. sinusitis, arthritis, new sensory peripheral neuropathy; and 4. sinusitis, epistaxis, fatigue/weight loss and enlarging pulmonary nodules.
Conclusions: In this small cohort of WG patients, clinical improvement and B cell depletion occurred in all patients after treatment with RIT. However, all 4 relapsed despite B cell depletion. These cases demonstrate that absence of detectable peripheral blood B cells does not preclude the possibility of WG relapse. Whether such relapses were related to the influence of B cells in lymphoid organs or bone marrow mediating injury or yet other pathways of immune-mediated disease is unknown.

 E.S. Molloy, None; C.L. Koening, None; J. Hernandez-Rodriguez, None; T.M. Clark, None; C.A. Langford, None; G.S. Hoffman, None.