DMT17
Safety of Ocrelizumab in Patients with Relapsing-Remitting Multiple Sclerosis with Suboptimal Response to Prior Disease-Modifying Therapies: Data from the CASTING Study
Patients with relapsing-remitting multiple sclerosis (RRMS) often experience disease activity despite receiving a disease-modifying therapy (DMT). The Phase IIIb CASTING study (NCT02861014) evaluated the efficacy/safety of ocrelizumab (OCR) in patients with RRMS who had a suboptimal response to ≥6 months’ treatment with 1 or 2 prior DMTs.
Objectives:
To evaluate CASTING 2-year safety outcomes by subgroups, including age and prior DMT.
Methods:
Patients (N=680; Expanded Disability Status Scale score ≤4.0; discontinued prior DMT due to suboptimal response) received intravenous OCR 600 mg every 24 weeks for 96 weeks. Safety outcomes included adverse events (AEs), serious AEs (SAEs), AEs ≥Grade 3, discontinuations for AEs, infections, serious infections (SIs), and lymphocyte count.
Results:
Safety outcomes were comparable between patients with 1 prior DMT vs 2 prior DMTs (% of patients with an event): AEs, 89.3% vs 88.8%; SAEs, 7.5% vs 6.7%; AEs ≥Grade 3, 11.9% vs 11.9%; AEs leading to discontinuation, 1.2% vs 0.7%; infections, 67.6% vs 65.8%; SIs, 1.9% vs 1.1%. Safety outcomes were also comparable between patients aged ≤40 years vs >40 years (% of patients with an event): AEs, 88.8% vs 89.9%; SAEs, 7.4% vs 6.5%; AEs ≥Grade 3, 11.4% vs 13.6%; AEs leading to discontinuation, 1.4% vs 0%; infections, 66.3% vs 68.6%; SIs, 1.8% vs 1.2%. Last DMT before OCR had little impact on the safety outcomes (% of patients with an event [interferons vs glatiramer acetate vs dimethyl fumarate vs teriflunomide vs fingolimod]): AEs, 87.4% vs 89.7% vs 91.7% vs 92.3% vs 86.0%; SAEs, 8.1% vs 9.5% vs 3.6% vs 12.3% vs 6.2%; AEs ≥Grade 3, 11.6% vs 11.2% vs 11.9% vs 18.5% vs 10.1%; AEs leading to discontinuation, 1.0% vs 1.7% vs 1.2% vs 1.5% vs 0%; infections, 66.2% vs 68.1% vs 69.0% vs 67.7% vs 62.8%; SIs, 2.0% vs 0.9% vs 1.8% vs 3.1% vs 0.8%. At Week 96, median (range) lymphocyte count (x109/L) was comparable between patients with 1 prior DMT (1.60 [0.39–3.60]) vs 2 prior DMTs (1.57 [0.69–3.51]), patients aged ≤40 years (1.60 [0.69–3.60]) vs >40 years (1.50 [0.39–3.07]) and last DMT before OCR: interferons (1.64 [0.39–3.30]); glatiramer acetate (1.63 [0.70–3.60]); dimethyl fumarate (1.58 [0.70–2.97]); teriflunomide (1.71 [0.80–3.51]); fingolimod (1.34 [0.69–3.10]). No hematological abnormalities were seen in patients treated with OCR, regardless of previous DMTs or age.
Conclusions:
The safety profile was comparable between subgroups, including age and number/type of prior DMTs. No new safety signals were identified.