Impact of Time Since Diagnosis on Inebilizumab Efficacy: Post-hoc Phase 3 MINT Trial Data Analysis

ObjectiveTo determine if response to inebilizumab, a monoclonal antibody targeting CD19+ B cells, differs by time since diagnosis of generalized myasthenia gravis in the MINT phase 3 trial. BackgroundGeneralized myasthenia gravis (gMG) is characterized by autoreactive B cells producing anti–acetylcholine receptor antibodies (AChR+), anti–muscle-specific kinase antibodies (MuSK+), or other autoantibodies. The MINT primary endpoint (change in Myasthenia Gravis Activities of Daily Living [MG-ADL] score) was achieved, supporting the efficacy of inebilizumab in gMG. Design/MethodsParticipants with AChR+ or MuSK+ seropositive gMG were enrolled in MINT (NCT04524273). Participants underwent a protocol-specified glucocorticoid taper to ≤5 mg/day and were randomized 1:1 to 300mg inebilizumab or placebo for 26 (MuSK+) or 52 (AChR+) weeks. Changes from baseline (CFBs) in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores by time since diagnosis (date of first dose in the randomized, controlled period minus gMG diagnosis date) were examined in this post hoc analysis. ResultsOverall, 238 participants (AChR+, 190; MuSK+, 48) were enrolled and randomized to inebilizumab or placebo. The least squares mean (LSM) CFB in MG-ADL score was overall numerically greater for inebilizumab vs placebo at week (W) 26 for participants with time since diagnosis of <1 year (–5.4 vs –3.0), ≥1y–<4y (–4.3 vs –1.8), and ≥4y (–3.7 vs –2.5); the LSM CFB in QMG score was also numerically greater for inebilizumab vs placebo at W26 (<1y, –5.2 vs –4.0; ≥1y–<4y, –6.4 vs –2.2; ≥4y, –4.0 vs –1.9). Significant improvements from baseline with inebilizumab vs placebo were observed at W52 for MG-ADL (AChR+: <1y, –5.7 vs –2.3; ≥1y–<4y, –5.0 vs –2.7; ≥4y, –4.0 vs –1.5) and QMG (AChR+: <1y, –7.4 vs –1.8; ≥1y–<4y, –8.3 vs –2.9, ≥4y, –3.9 vs –0.5) scores. ConclusionsThe efficacy of inebilizumab appears independent of time since diagnosis, although the small size of subgroups limits firm conclusions.