Efficacy and Safety of Ocrelizumab in Patients with Relapsing-Remitting Multiple Sclerosis with Suboptimal Response to Prior Disease-Modifying Therapies: Primary Analysis from the Phase 3b CASTING Single-Arm, Open-Label Trial.

BACKGROUND Using the treatment goal of 'no evidence of disease activity' (NEDA) incorporating MRI rebaselining, we assessed the efficacy of ocrelizumab in patients with relapsing-remitting multiple sclerosis with a prior suboptimal response, defined by MRI or relapse criteria, to one or two disease-modifying therapies (DMTs). METHODS CASTING was a prospective, international, multicenter, single-arm, open-label phase III trial (NCT02861014). Patients (Expanded Disability Status Scale [EDSS] score ≤4.0; discontinued prior DMT of ≥6 months duration due to suboptimal disease control) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. The primary endpoint was NEDA (defined as: absence of relapses, disability progression, and inflammatory MRI measures, with prespecified MRI rebaselining at Week 8) over 96 weeks. RESULTS A total of 680 patients were enrolled, 167 (24.6%) based on MRI activity only. At Week 96, 74.8% (95% CI, 71.3-78.0; n/N=492/658) of patients had NEDA. NEDA was highest among patients enrolled due to MRI activity alone (80.6% [68.6-89.6] n/N=50/62) versus for relapse (75.1% [69.0-80.6] n/N=172/229) or relapse with MRI (70.5% [60.0-79.0] n/N=74/105). NEDA across subgroups was highest in patients with baseline EDSS score <2.5 (77.2% [72.8-81.2] n/N=315/408). NEDA was higher in patients receiving one prior DMT (77.6% [73.2-81.6] n/N=312/402) versus two (70.3% [64.3-75.8] n/N=180/256). CONCLUSIONS In patients switching therapy due to suboptimal disease control, treatment with ocrelizumab led to an overall high NEDA rate across a wide range of disease-related and demographic subgroups, regardless of prior treatment background, with no new safety signals detected.