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Abstract: TH-PO681

Obinutuzumab in Combination with Avacopan in Rituximab-Resistant ANCA-Associated Vasculitis (AAV)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Radhakrishnan, Yeshwanter, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Specks, Ulrich, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Zand, Ladan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Introduction

Rituximab (RTX) is now considered the standard for induction (along with glucocorticoid) and maintenance therapy of patients with AAV. We report 2 patients with AAV who had active disease despite RTX therapy and were successfully treated with combination of Obinutuzumab (OBZ) (a type II anti-CD20) and Avacopan (C5aR antagonist).

Case Description

Patient 1: 80-year old female with a 10-year history of microscopic polyangiitis treated with mycophenolate (MPA) (for 6 years) and prednisone (PRED). She relapsed after being off immunosuppression for 2 years and was re-initiated on MPA therapy. Due to lack of response, she was switched to RTX induction 1g x 2 doses 2 weeks apart with PRED. At the time of RTX induction, serum creatinine (Scr) was 1.5 with MPO-ANCA titers > 8.0 U and hematuria (3-10 RBC/HPF). She was continued on RTX maintenance therapy (1g) every 6-months. However, despite RTX therapy (18 months) and CD20+ B cell of zero, she had rising Scr 2.1 mg/dL with persistent hematuria and MPO titers > 8.0 U. Repeat biopsy showed active necrotizing glomerulonephritis (GN). Therefore, she received OBZ 1g x 2 doses 2weeks apart with Avacopan 30 mg twice daily. At last follow up (9 months after OBZ), her Scr is stable at 2.0 mg/dL, hematuria completely resolved and MPO is down to 1.1 U. She has not experienced any adverse events.
Patient 2: 47-year-old female was diagnosed with AAV after presenting with a Scr of 2.6, hematuria (3-10 RBC/HPF), MPO titers > 8.0 U and a biopsy that showed pauci-immune necrotizing GN. She was initially treated with RTX 375 mg/m2 weekly for 4 doses and PRED. She was continued on RTX (1g) every 6 months. Although her Scr initially improved to 1.5 mg/dL, her MPO remained persistently > 8.0. Subsequently, she was noted to have a worsening Scr that peaked at 2.4 mg/dL with hematuria (100/HPF) and MPO > 8.0 U despite therapy with RTX. CD20+ B cells were zero. A repeat kidney biopsy showed active necrotizing GN. She received 1 dose of OBZ 1g, Avacopan 30 mg twice daily and prednisone. Six months following OBZ, Scr is stable at 2.2 mg/dL, hematuria resolved and MPO titers are down to 5.8 U.

Discussion

OBZ with Avacopan can be an effective strategy in AAV patients resistant to RTX. The efficacy of this combination should be evaluated through a randomized clinical trial to determine outcomes and adverse effects.