Validation of the Finnish version of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and evaluation of the applicability of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and the Fatigue Scale for Motor and Cognitive Functions (FSMC)

Objectives Cognitive impairment is frequent in multiple sclerosis (MS) as approximately half of the patients manifest some degree of cognitive impairment. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been designed for brief cognitive evaluation. The purpose of the study was to validate the BICAMS along with the Finnish versions of one self-rating questionnaire each for cognition and fatigue. Methods A total of 65 MS patients and 45 healthy controls (HC) were assessed with the BICAMS, the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), and the Fatigue Scale for Motor and Cognitive Functions (FSMC) twice, approximately within nine days. Results MS patients scored markedly lower than the HCs on each of the three tests of the BICAMS. Of the patients, 60% scored at least 1.5 SD below the mean of the HCs on at least one test; 49% on the SDMT, 26% on the CVLT-II, and 28% on the BVMT-R. Correlation coefficients for the repeated measurement were between 0.75 and 0.89 for the three tests in the whole study sample. MS patients reported more cognitive symptoms and more fatigue than the HCs. Cronbach's alpha was 0.94 for the MSNQ and 0.98 for the FSMC. Correlation coefficient for the repeated measurement was 0.91 for the MSNQ and between 0.92 and 0.94 for the FSMC scores for the whole study sample. Conclusions The present study supports the validity of the Finnish version of the BICAMS. The SDMT was the most sensitive of the three BICAMS tests and showed cognitive impairment in half of the patients. The Finnish versions of the MSNQ and the FSMC proved useful tools in approaching concerns related to cognition and fatigue.Peer reviewe

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis : APLIOS, a randomized phase-2 study

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion