A multicentre, open label, single-arm, phase 3b study (CONSONANCE) to assess the effectiveness and safety of ocrelizumab in patients with primary and secondary progressive multiple sclerosis: year-1 interim analysis
Giancarlo Comi1, Robert Bermel2, Amit Bar-Or3, Marisa McGinley2, Douglas Arnold4, Roland Henry5, Ralph Benedict6, Pavan Bhargava7, Helmut Butzkueven8, Declan Chard9, Guy Gherardi10, Owain Howell11, Christine Lebrun-Frenay12, Letizia Leocani13, Agne Kazlauskaite10, Thomas Kuenzel10, Xavier Montalban14, Maria Pia Sormani15, Finn Sellebjerg16, Licinio Craveiro10, Catherine Lubetzki17
1Vita Salute San Raffaele University, Casa di Cura del Policlinico, 2Cleveland Clinic, 3University of Pennsylvania, 4McGill University and NeuroRx, 5University of California, 6University at Buffalo, 7John Hopkins University, 8Monash University, 9NMR Research Unit, University College London and National Institute for Health Research, University College London Hospitals, 10Roche, 11Swansea University, 12Centre Hospitalier Universitaire de Nice, Université Côte d’Azur UR2CA, 13Vita Salute San Raffaele University, 14Vall d'Hebron University Hospital, 15University of Genoa, 16Copenhagen University Hospital, 17APHP Sorbonne University
Objective:
To report year-1 interim analysis results of 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:
Few treatment options are available for patients with progressive MS, with ocrelizumab being the only approved treatment for PPMS. CONSONANCE is the first trial to explore the effect of ocrelizumab in both forms of progressive MS.
Design/Methods:
Eligible patients receive ocrelizumab 600 mg every 24 weeks for up to 4 years. Primary endpoints include (1) No Evidence of Progression (NEP) defined as absence of 24‐week confirmed clinical progression (as measured by increase in EDSS score; ≥20% increase in 25-foot walk test [25FWT]; ≥20% increase in nine-hole peg test [9HPT]) and (2) No Evidence of Progression or Active Disease (NEPAD) defined as NEP plus absence of protocol-defined relapses, new/enlarging T2 lesions (N/E-T2) or T1 gadolinium-enhancing lesions. 
Results:
The analysis included 629 (SPMS 325; PPMS 304) patients (mean age 48.5 years, 52.3% female). At baseline, median (interquartile-range) EDSS score was 5.5 (4.0–6.0), and times for 9HPT and 25FWT were 32.6 (15.7) and 14.9 (17.0) seconds, respectively. During year 1, 457/610 (74.9%) patients showed NEP (SPMS 78.2%; PPMS 71.3%) and 361/615 (58.7%) had NEPAD (SPMS 58.9%; PPMS 58.4%). Progression was mostly driven by 25FWT (16.1%), and activity by N/E-T2 (19.3%, detected almost exclusively in the first 6 months). In total, 473/629 (75.2%) patients had ≥1 adverse event (AE), and 42/629 (6.7%) experienced ≥1 serious AE. One death was reported.
Conclusions:

Effectiveness and safety were similar for patients with SPMS and PPMS and outcomes were consistent with results from the phase 3 trial ORATORIO, suggesting treatment with ocrelizumab over 1 year is associated with low levels of disease progression and activity in both forms of progressive MS. Longer-term treatment in CONSONANCE is ongoing.