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PRO-MSACTIVE Data Highlights Efficacy, Safety, and Patient-Reported Outcomes of Ocrelizumab in Relapsing MS

More than half of the cohort achieved no evidence of disease activity and few patients showed disability progression after 48 weeks of treatment with ocrelizumab.

Findings from the PRO-MSACTIVE study, a phase 4 trial (NCT03589105) tended to mimic current practice, confirmed the treatment benefit of ocrelizumab (Ocrevus; Genentech) in patients with relapsing multiple sclerosis (MS). Safety data was reassuring and consistent with results from previous trials and the known safety profile of ocrelizumab since commercialization.

Using a cohort of 376 patients with relapsing-remitting MS (RRMS) and 46 with secondary progressive MS (SPMS), 63.3% (95% CI, 58.5-67.9) of the total cohort were free of disease activity at week 48, including 62.2% (95% CI, 57.1-67.2) of those in the relapsing group and 71.7% (95% CI, 56.5-84.0) in the secondary progressive group. Overall, 58.5% (95% CI, 53.7-63.3) of patients achieved no evidence of disease activity at week 48, with a higher proportion of patients achieving this in the SPMS group (65.2%; 95% CI, 49.8%-748.6) than the relapsing MS group (57.7%; 95% CI, 52.5-62.8).

Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in Europe for the treatment of relapsing and primary progressive MS on the basis of the phase 3 OPERA I and II studies (NCT01247324; NCT01412333); however, there had been limited data on the agent’s efficacy in relapsing MS according to the Lublin definition of activity. Senior investigator Christine L. Frenay, MD, PhD, FAAN, head, Inflammatory Neurological Disorders Clinical Research Unit, Centre Hospitalier de Gonesse, and colleagues aimed to provide additional data on ocrelizumab’s efficacy, safety, and patient-reported outcome (PRO) measures in those with relapsing MS in a pragmatic setting.

In terms of disease activity, 10.9% (46 of 4222) of patients experienced at least 1 protocol-defined or clinical relapse up to week 48. Among these patients, 78.3% (n = 36) experienced a single relapse, and the majority of relapses occurred within 6 months following ocrelizumab initiation. At week 48, the overall adjusted annualized relapse rate (ARR) was 0.14, and was higher in patients with RRMS than then SPMS group (0.15 and 0.09, respectively).

Additional findings from the study showed that 67.8% (286 of 422) of the cohort had no evidence of MRI activity; however, the proportion was higher in the SPMS group (76.1%) than the RRMS group (66.8%). After excluding missing data from the analysis, the proportion of patients with no evidence of MRI activity increased (73.3%). Disability progression, observed at week 24 and confirmed at week 48, was found in only 13.0% (95% CI, 10.0-16.6) of patients, and was higher in the SPMS group (17.4% vs 12.5%).

In terms of safety, 89.3% (n = 377) of patients experienced at least 1 emergent adverse event (AE), the most common of which were infusion-related reactions related ocrelizumab or to the pre-medication prophylaxis with methylprednisolone and/or antihistamine drug (47.6%). Headache (14.7%), nasopharyngitis (11.4%), and urinary tract infection (10.0%) rounded out the other top observed AEs. Serious AEs were found in 8.5% (n = 36) of the population, with a higher proportion seen in patients with SPMS (15.2%) than RRMS (7.7%).

Patients completed several self-reported PRO questionnaires during the study, including the MS symptoms’ severity scale (SymptoMScreen), Modified Fatigue Impact Scale (MFIS), EuroQol 5-dimension 5-level version (EQ-5D-5L with visual analog scale), Multiple Sclerosis International Quality of Life questionnaire, Work Productivity and Activity Impairment scale: Specific Health Program (WPAI:SHP), and Treatment Satisfaction Questionnaire for Medication (TSQM-14). PRO questionnaires that assessed aspects of quality of life showed a similar trend: the total score and per dimension of each scale remained broadly stable from baseline to week 48, regardless of the type of relapsing MS.

Overall, the impact of MS on patient daily life was stronger at week 48 in those with a high Expanded Disability Status Scale (EDSS) score at baseline, regardless of the PRO used. Additionally, patient satisfaction, assessed using the TSQM-14, showed a mean global score of 60.3 (±19.5) at D15 that slightly improved until week 48. Additionally, scores per dimension on the TSQM-14 slightly improved as well, in particular in RRMS for effectiveness (median change, 11.1) and in patients with a low EDSS baseline score (median change of 20.0 when EDSS <2.0).

REFERENCES
1. Manchon E, Laplaud D, Vukusic S, et al. Efficacy, safety, and patient-reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: final results from the PRO-MSACTIVE study. Mult Scler & Relat Disor. 2022;104109. doi:10.1016/j.msard.2022.104109