P021 Obinutuzumab induces histological remission and deep kidney parenchymal B-cell depletion in patients with lupus nephritis: exploratory analyses from the REGENCY trial

Abstract Background/Aims The REGENCY trial (NCT04221477) demonstrated superiority of obinutuzumab (OBI) plus standard therapy (+ST) vs placebo (PBO) +ST in achieving complete renal response (CRR) at week 76 (W76) in adults with active lupus nephritis (LN). These exploratory analyses aimed to evaluate histological remission and kidney tissue-level B-cell depletion at W76 in patients treated with OBI+ST vs PBO+ST. Methods Paired baseline and W76 kidney biopsies from REGENCY participants with biopsy-proven proliferative LN were analysed. Histological analysis: 64 biopsies (32 OBI+ST, 32 PBO+ST) were evaluated using the 2018 ISN/RPS LN classification, along with the NIH activity (AI) and chronicity indices. The proportion of patients achieving histological or near-histological remission (AI = 0 or ≤ 1) was determined. B-cell analysis: 29 participants (14 OBI+ST, 15 PBO+ST) were assessed. CD79a+/CD138− B cells were quantified by immunofluorescence microscopy and digital whole-slide analysis. Changes in B-cell counts at W76 were compared using an ANCOVA model, adjusting for baseline B-cell counts and stratification factors. Results Baseline characteristics were balanced, despite higher tissue B-cell levels in the OBI+ST group (Table 1). At W76, significantly more patients achieved AI = 0 or ≤ 1 with OBI+ST vs PBO+ST. Among patients not achieving CRR, 52.6% (10/19) in the OBI+ST group had an AI = 0 at W76, vs 8.3% (2/24) in the PBO+ST group. Most patients in the OBI+ST group had substantial drops in kidney tissue B-cell counts by W76. The adjusted mean change in B-cell counts from baseline to W76 was −28.5 (95% CI, −33.3 to − 23.6) for OBI+ST vs − 11.9 (95% CI, −16.6 to − 7.2) for PBO+ST, a significant difference of − 16.6 (95% CI, −23.4 to − 9.7; P