A multicenter, open label, single-arm, phase 3b study (CONSONANCE) to assess efficacy of ocrelizumab in patients with primary and secondary progressive multiple sclerosis: year 1 interim analysis of cognition outcomes
Ralph Benedict1, Maria Pia Sormani2, Marisa McGinley3, Douglas Arnold4, Amit Bar-Or5, Robert Bermel3, Pavan Bhargava6, Declan Chard7, Guy Gherardi8, Roland Henry9, Owain Howell10, Christine Lebrun-Frenay11, Letizia Leocani12, Catherine Lubetzki13, Agne Kazlauskaite8, Thomas Kuenzel8, Xavier Montalban14, Finn Sellebjerg15, Giancarlo Comi16, Licinio Craveiro8, Helmut Butzkeuven17
1University at Buffalo, 2University of Genoa, 3Cleveland Clinic, 4McGill University and NeuroRx, 5University of Pennsylvania, 6John Hopkins University, 7NMR Research Unit, University College London and National Institute for Health Research, University College London Hospitals, 8Roche, 9University of California, 10Swansea University, 11Centre Hospitalier Universitaire de Nice, Université Côte d’Azur UR2CA, 12Vita Salute San Raffaele University, 13APHP Sorbonne University, 14Vall d'Hebron University Hospital, 15Copenhagen University Hospital, 16Vita Salute San Raffaele University, Casa di Cura del Policlinico, 17Monash University
Objective:
To report year 1 interim analysis of cognitive outcomes in the single-arm, phase 3b CONSONANCE study (NCT03523858) designed to evaluate effectiveness and safety of ocrelizumab in patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS).
Background:
Cognitive impairment is very common in patients with MS and negatively affects quality of life. CONSONANCE is the first trial to explore the effect of ocrelizumab on cognitive outcomes in both forms of progressive MS. 
Design/Methods:
Eligible patients receive ocrelizumab 600 mg every 24 weeks for up to 4 years. Yearly cognitive assessments include: oral response version of the Symbol Digit Modalities Test (SDMT), and three immediate recall trials of the Brief Visuospatial Memory Test-Revised (BVMT-R). Mean percentage change from baseline (CfB) and change in SDMT ≥4 points were calculated.
Results:
The analysis included 629 (SPMS 325; PPMS 304) patients (mean age 48.5 years, 52.3% female). At baseline, mean (SD) BVMT-R total score was 18.8 (8.1) points (SPMS 18.6 [8.0]; PPMS 18.9 [8.2]), and at year 1, a mean (SD) CfB of +14.9% (69.8%) (SPMS 15.0% [71.1%]; PPMS 14.7% [68.4%]) was observed. At baseline, mean (SD) SDMT score was 42.3 (13.8) (SPMS 42.0 [13.7]; PPMS 42.6 [13.9]), and 45.3% (269/594) of patients had a score <43 points. At year 1, a mean (SD) CfB of +10.7% (72.8%) (SPMS 12.6% [93.3%]; PPMS 8.6% [39.1%]) was reported. Clinically meaningful improvement (increase of ≥4 points) and worsening (decrease of ≥4 points) in SDMT was observed in 34.4% (186/540) (SPMS 34.8%; PPMS 34.1%) and 30.0% (162/540) (SPMS 33.0%; PPMS 26.7%) of patients, respectively. 
Conclusions:
Patients with progressive MS enrolled into CONSONANCE exhibit moderate-to-severe dysfunction in information processing speed and visuospatial memory. At year 1, treatment with ocrelizumab was associated with stable or improved cognitive function in most patients, and observations were similar in patients with SPMS and PPMS.