Avacopan or Glucocorticoids for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Rapidly Progressive Glomerulonephritis.

Introduction: The best immunosuppressive regimen to treat severe forms of antineutrophil cytoplasmic autoantibody (ANCA)-associated rapidly progressive glomerulonephritis (RPGN) remains elusive because patients with the lowest estimated glomerular filtration rate (eGFR) have been excluded from most studies, and kidney biopsy has not been a prerequisite for inclusion. Methods: In a cohort of 70 adult patients with severe ANCA-RPGN (eGFR: 0-30 ml/min per 1.73 m Results: Fifty patients received a GC regimen combined with cyclophosphamide (CYC) (30%), rituximab (RTX, 54%) or a combination of both (16%), whereas 20 patients received avacopan combined with RTX (90%) or RTX plus CYC (10%). Half of the patients in each group received plasma exchanges. The percentage of crescentic glomeruli (a reliable marker of kidney vasculitis activity) correlated with eGFR at presentation, whereas the percentage of glomerulosclerosis (a surrogate marker for chronic kidney lesions) correlated with maximal kidney improvement at month 6. After adjustment for histopathology, the induction regimen (RTX, CYC, or both) as well as the use of GCs or avacopan-based induction regimen were associated with similar kidney response at month 6, whatever end point was used. Reversible hepatitis requiring avacopan withdrawal occurred in 3 patients. No new safety signal was identified in the avacopan group. Conclusion: At months 6 and 12, patients with severe forms of ANCA-RPGN and receiving avacopan plus a short course of GCs have similar kidney recovery rates to patients receiving GC regimen.