Document resource
Objectives Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody that induces potent and sustained B-cell depletion, is approved for active lupus nephritis. The Phase III, multicenter, randomized, double-blind, placebo-controlled ALLEGORY trial ( NCT04963296) evaluated obinutuzumab compared with placebo when added to standard therapy (ST) in adults with active systemic lupus erythematosus (SLE).Methods Patients on ST (antimalarial and/or immunosuppressant and/or prednisone [or equivalent]) were randomized 1:1 to receive 1000 mg intravenous obinutuzumab or placebo on Day 1 and Weeks (W) 2, 24 and 26. The primary endpoint was SLE Responder Index-4 (SRI-4) response at W52.Results Of 303 patients, 151 received obinutuzumab and 152 received placebo. Mean baseline SLE Disease Activity Index 2000 scores were 13.1 and 13.2 in the obinutuzumab and placebo groups, respectively; approximately 65% had scores >=12. At W52, a significantly higher proportion of the obinutuzumab versus placebo group achieved an SRI-4 response (76.7% vs 53.5%; adjusted difference, 23.1 percentage points; 95% confidence interval [CI], 12.5 to 33.6; P<0.0001). Obinutuzumab was superior to placebo with statistically significant benefit in all key secondary endpoints ( table 1): British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment response, sustained glucocorticoid reduction, sustained SRI-4 response, SRI-6 response and time to BILAG flare. More patients in the obinutuzumab versus placebo group achieved the prespecified additional (non-type 1 error controlled) endpoints of Definition of Remission in SLE (35.1% vs 13.8%; adjusted difference, 21.2 percentage points; 95% CI, 11.8 to 30.5) or Lupus Low Disease Activity State (57.6% vs 25.0%; adjusted difference, 32.6 percentage points; 95% CI, 22.3 to 43.0) at W52. In the obinutuzumab versus placebo groups, respectively, grade >=3 adverse events (AEs) were observed in 25 (16.6%) and 21 (13.9%) patients, and serious AEs occurred in 24 (15.9%) and 18 (11.9%) patients (table 2), with the most frequent being pneumonia (2.0%) and upper respiratory tract infection, urinary tract infection and infusion-related reactions (1.3% each) among obinutuzumab-treated patients.Abstract LBS1:01 Table 1Primary and secondary efficacy endpoint results in the ALLEGORY intention-to-treat populationAbstract LBS1:01 Table 2Adverse events through week 52 in the ALLEGORY safety populationConclusions Obinutuzumab was superior to placebo in achieving the primary and five key secondary endpoints. No new safety signals were identified. ALLEGORY provides evidence that obinutuzumab, when added to ST, is more effective for active SLE than ST alone.