DX67
Impact of Ocrelizumab on Cognition in Patients at Increased Risk of Developing Progressive Disease
Cognitive impairment is common in patients with multiple sclerosis (MS) and considerably impacts quality of life. The probability of cognitive deficits increases with progressive disease. In a pooled analysis of two identical Phase III studies in patients with relapsing MS (RMS) (OPERA I; OPERA II), ocrelizumab treatment was associated with significant improvements in cognitive performance over 96 weeks vs interferon (IFN) β-1a using the Symbol Digit Modalities Test (SDMT).
Objectives:
To determine the impact of ocrelizumab vs IFN β-1a on cognition using the SDMT in patients with RMS at increased risk of progressive disease, with or without baseline cognitive impairment.
Methods:
Patients in the OPERA trials received ocrelizumab 600 mg every 24 weeks or subcutaneous IFN β-1a 44 μg three times weekly for 96 weeks. Patients with a baseline Expanded Disability Status Scale score ≥4 and a pyramidal Kurtzke Functional Systems Score ≥2 were considered to be at increased risk of developing progressive disease. The SDMT was administered at baseline and every 12 weeks, and scores ≥2 SD below population norms were considered moderate impairment. Analyses included mean change in SDMT score and the proportion of patients achieving clinically meaningful improvements (defined as a ≥4-point increase) over 96 weeks.
Results:
Ocrelizumab-treated (n=186) and IFN β-1a−treated (n=180) patients at increased risk of developing progressive disease had mean (SE) baseline SDMT scores of 39.4 (1.6) and 39.5 (1.6), respectively. Over 96 weeks, a significantly greater mean (SE) improvement from baseline SDMT score was observed with ocrelizumab (6.2 [1.2]) vs IFN β-1a (2.6 [1.2]; p=0.023). Among the subgroup of patients with baseline SDMT impairment (ocrelizumab: n=116, mean [SE] SDMT score=27.9 [1.0]; IFN β-1a: n=107, mean [SE] SDMT score=28.2 [0.9]), ocrelizumab demonstrated a significantly greater mean (SE) improvement from baseline (10.5 [1.4]) vs IFN β-1a (6.0 [1.4]; p=0.011). A significantly greater proportion of ocrelizumab- vs IFN β-1a-treated patients at increased risk of developing progressive disease experienced improvements of ≥4 points on the SDMT by 48 weeks (51.2% vs 39.4%; p=0.040); benefits of ocrelizumab were maintained at 96 weeks (62.2% vs 46.5%; p=0.009).
Conclusions:
Ocrelizumab demonstrated a positive impact on cognition as measured by the SDMT in patients with RMS at increased risk of developing progressive disease, including those with baseline SDMT impairment.
Disclosures
Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA.