ABSTRACT
Introduction: The approval of ocrelizumab (OCR) for the treatment of primary progressive MS (PPMS) showed that the course of progressive MS (PMS) can be altered with effective treatment;however, direct evidence across the spectrum of PMS, including secondary progressive MS (SPMS), is still lacking. Objective(s): CONSONANCE (NCT03523858) is a single-arm, phase 3b, 4-year study designed to evaluate for the first time the effectiveness and safety of OCR in patients with SPMS or PPMS. Year 2 results are reported. Method(s): Patients with active or non-active PMS but showing disability progression in the past 2 years were enrolled. Primary outcomes are (1) proportion of patients with no evidence of progression (NEP) defined as no progression confirmed for >=24 weeks on Expanded Disability Status Scale (EDSS), no >=20% increase in timed 25-foot walk test (T25FWT), no >=20% increase in nine-hole peg test (9HPT) time, and no MS-related death or treatment discontinuation due to efficacy failure;(2) proportion of patients with no evidence of progression and no active disease (NEPAD) defined as NEP plus no protocol-defined relapse, no new/enlarging T2 lesions (N/E-T2, re-baselined at week 24), and no T1 gadolinium-enhanced lesions. Result(s): Patients (n=629;SPMS n=324, PPMS n=305) had mean (SD) age of 48.5 (9.2) years and 52.3% were female. At baseline (BL), median (IQR)/mean (SD) EDSS scores were 6.0 (4.5- 6.0)/5.3 (1.3) for patients with SPMS and 5.0 (4.0-6.0)/4.8 (1.3) for PPMS. Overall median times for 9HPT and T25FWT were 27.9 and 9.4 seconds, respectively. Over 2 years, 311/586 (53.1%) patients had NEP (SPMS 55.8%;PPMS 50.2%;progression was mostly driven by increases in T25FWT) and 283/588 (48.1%) had NEPAD (SPMS 49.5%;PPMS 46.7%;acute activity predominantly driven by N/E-T2 lesions). Overall EDSS remained stable from BL to year 2 (mean [SD] change of +0.07 (0.79) points). In patients with EDSS >=2.0 at BL (n=526), 24-week confirmed disability improvement in any of the components (EDSS, T25FWT, 9HPT) was observed in 29.8% of cases. Rates of serious AEs and serious infections were 7.6/100PY and 3.2/100PY, respectively. Eight deaths were reported (COVID=6, pulmonary embolism=1, non-small cell lung cancer=1). Conclusion(s): Over a 2-year period, treatment with OCR was associated with comparable rates of NEP and NEPAD in patients with SPMS and PPMS, and with functional improvement in about one-third of patients. Safety outcomes were consistent with known safety profile.