Assessing Sustained B-Cell Depletion and Disease Activity in a French Multiple Sclerosis Cohort Treated by Long-Term IV Anti-CD20 Antibody Therapy.

Few studies have investigated sustained B-cell depletion after long-term intravenous (IV) anti-CD20 B-cell depleting therapy (BCDT) in multiple sclerosis (MS) with respect to strict and/or minimal disease activity. The main objective of this study was to investigate how sustained B-cell depletion after BCDT influences clinical and radiological stability as defined by "no evidence of disease activity" (NEDA-3) and "minimal evidence of disease activity" (MEDA) status in MS patients at 12 and 18 months. Furthermore, we assessed the frequency of serious adverse events (SAE), and the influence of prior lymphocytopenia-inducing treatment (LIT) on lymphocyte subset counts and gammaglobulins in MS patients receiving long-term BCDT. We performed a retrospective, prospectively collected, study in a cohort of 192 MS patients of all clinical phenotypes treated by BCDT between January 2014 and September 2021. Overall, 84.2% and 96.9% of patients attained NEDA-3 and MEDA status at 18 months, respectively. Sustained CD19+ depletion was observed in 85.8% of patients at 18 months. No significant difference was observed when comparing patients achieving either NEDA-3 or MEDA at 18 months and sustained B-cell depletion. Compared to baseline levels, IgM and IgG levels on BCDT significantly decreased at 6 months and 30 months, respectively. Patients receiving LIT prior to BCDT showed significant CD4+ lymphocytopenia and lower IgG levels compared to non-LIT patients. Grade 3 or above SAEs were rare. As nearly all patients achieved MEDA at 18 months, we suggest tailoring IV BCDT after 18 months given the occurrence of lymphocytopenia, hypogammaglobulinemia, and SAE after this time point.

Biology of subjective cognitive complaint amongst geriatric patients: vitamin D involvement.

BACKGROUND: Insufficiency in vitamin D, a neurosteroid hormone, is associated with cognitive decline in older adults. The impact on the subjective perception of cognitive decline has not yet been examined. The objective of this cross-sectional hospital-based study was to determine whether vitamin D insufficiency was associated with subjective cognitive complaint amongst geriatric patients. METHODS: Ninety-nine consecutive Caucasian in- and outpatients recruited in the 'Cognition and LIPophilic vitamins' (CLIP) study, who had no advanced cognitive disorders (i.e., Mini-Mental State Examination score≥20) and who took no vitamin D supplements, were categorized into 2 groups based on vitamin D insufficiency (i.e., serum 25-hydroxyvitamin D≥75 nmol/L). Subjective cognitive complaint was examined using the Memory Complaint Questionnaire (MAC-Q; score 0-30, best). MAC-Q score<15 out of 30 defined severe cognitive complaint. Age, gender, body mass index, education level, comorbidity burden, functional autonomy, mood, and serum concentrations of parathyroid hormone, calcium, thyroid-stimulating hormone and vitamin B12, and estimated glomerular filtration rate were used as potential confounders. RESULTS: Compared to participants with serum 25OHD>75 nmol/L, those with vitamin D insufficiency (n=89) had a lower mean MAC-Q score (14.9±2.9 versus 17.1±1.6, P=0.02) and more often a MAC-Q score<15 (52.8% versus 10.0%, P=0.01). Vitamin D insufficiency was inversely associated with the MAC-Q score (adjusted ß=-2.84, P=0.03), and positively associated with severe cognitive complaint (adjusted OR=10.07, P=0.03). CONCLUSION: Vitamin D insufficiency was associated with subjective cognitive complaint in the studied cohort of geriatric patients.