A pair of datasets from the phase 3b CASTING study of ocrelizumab (Ocrevus; Genentech) suggest that patients treated with the agent experienced high rates of no evidence of disease activity status regardless of prior DMT exposure.
Heinz Wiendl, MD
New results from the phase 3b CASTING study (NCT02861014) suggest that a wide range of disease-related and demographic subgroups of patients with multiple sclerosis (MS) who are treated with ocrelizumab (Ocrevus; Genentech) achieve high rates of no evidence of disease activity (NEDA) status after 2 years. This status was reached regardless of prior exposure to disease-modifying therapies (DMTs).1
Additionally, a second dataset from CASTING revealed that individuals with relapsing MS who had a suboptimal response to prior treatment experienced symptom improvement after 2 years across the majority of domains measured by SymptoMScreen, a patient-reported outcome tool designed to rapidly assess symptom limitations across 12 symptoms commonly reported in MS. These gains were most pronounced for sensory, fatigue, and vision-related symptoms.2
The data were presented at MS Virtual 2020, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, the first set by Heinz Wiendl, MD, head, Weindl Lab, Clinic for Neurology, Institute for Translational Neurology, University Hospital Münster, and the second set by Ilya Kister, MD, associate professor, Department of Neurology, NYU Grossman School of Medicine, and director, Neuromyelitis Optica Treatment and Research Program, NYU Langone Health.
Wiendl and colleagues’ data included 680 patients with a baseline Expanded Disability Status Scale (EDSS) score of 2.1 (standard deviation [SD], 1.1), of which 411 (60.4%) had been treated with 1 prior oral or injectable DMT and 269 (39.6%) had been treated with 2 prior DMTs. MRI-only disease activity was the reason for enrollment for 167 patients (24.6%) while 238 (35%) had only relapse, and 275 (40.4%) had both.1
After the 2-year treatment period, 492 of 658 patients (74.8%) qualified for NEDA status (with MRI re-baselined at Week 8 of treatment). The highest rates of NEDA were observed in those who were enrolled due to only MRI activity (80.6%). Those with only relapses had NEDA at a rate of 75.1% and those with both had a rate of 70.5%.
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NEDA rates did not vary by age at baseline when patients were stratified by those aged 40 years and younger (74.7%) and those older than 40 years (75%).
Additionally, the NEDA rates across disease-related subgroups were the highest in the subgroups of those with baseline EDSS score <2.5 (77.2%), those with ≤1 relapse prior to enrollment (78.2%), and the event leading to enrollment occurring ≥6 months prior to study entry (75.8%). These groups were highest compared to their counterpart subgroups of those with EDSS scores of ≥2.5 (70.8%), with >1 relapse prior to enrollment (66.3%), and with the event leading to enrollment occurring <6 months prior to entry (71.0%).
Those who received 1 prior DMT experienced higher rates of NEDA (77.6%) than those with 2 prior DMTs (70.3%), and the rates remained generally high when stratified by the last prior DMT received before enrollment—interferons, 81.1%; glatiramer acetate, 73.9%; dimethyl fumarate, 73.8%; teriflunomide 69.8%; fingolimod, 68.9%.
Meanwhile, the dataset presented by Kister et al. included the same cohort of patients to evaluate SymptoMScreen. Each domain of the tool is scored on a 7-point Likert scale, ranging from 0 (not affected) to 6([total limitation), and domain scores are summed to calculate a total score ranging from 0 to 72. SymptoMScreen was performed at baseline, Week 48 (which made up the 1-year interim data) and Week 96 (which made up the 2-year final data).2
Their findings showed that the total SymptoMScreen mean score reflected mild symptom burden at baseline (15.19 [SD, 12.67]) and improved significantly through the second year (13.62 [SD, 12.51]; P <.001). As mentioned, there were significant improvements reported by patients for sensory symptoms (Δ-0.28; P <.001), fatigue (Δ-0.23; P <.001), and vision (Δ-0.21; P <.001). Additionally, there were marked gains in symptoms of depression (Δ-0.15; P <.01) and dizziness (Δ-0.14; P <.01).
As well, the proportion of patients with ≥1 symptom causing at least moderate limitation (defined as a domain score ≥4) decreased from 31.6% at baseline to 26.3% at Year 2.
Non-significant improvements in symptom burden after 2 years were reported in the domains of walking (Δ-0.1), cognition (Δ-0.10), anxiety (Δ-0.07), bodily pain (Δ-0.05), hand function (Δ-0.03), and bladder control (Δ-0.01). There was a non-significant worsening was observed in the spasticity domain (Δ+0.04).
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