Cd19 cell count at baseline predicts b cell repopulation at 6 and 12 months in multiple sclerosis patients treated with ocrelizumab

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics. Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation rate (FR) and those with slow repopulation rate (SR). Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0,008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six-and twelve-month follow-ups, respectively). Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients

Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: Ne-PAL a pilot randomized controlled study

Background This study analysed the impact on palliative care outcomes of a new specialist palliative care service for patients severely affected by amyotrophic lateral sclerosis (ALS/MND), multiple sclerosis, Parkinson's disease and related disorders (multiple system atrophy progressive supranuclear palsy, MSA-PSP). Methods The design followed the Medical Research Council Framework for the evaluation of complex interventions. A phase II randomised controlled trial (RCT) was undertaken comparing an immediate referral to the service (FT, fast track) to a 16-week wait (standard track (ST), standard best practice) using a parallel arm design. The main outcome measures were Quality of Life (measured with Schedule for the Evaluation of Individual Quality of Life Direct Weight, SEIQoL-DW) and burden of the carers (Caregivers Burden Inventory, CBI), with secondary outcomes of symptoms, psychosocial and spiritual issues. Results 50 patients severely affected by neurodegenerative conditions and their informal family carers were randomised: 25 FT, 25 ST. At baseline (T0), there were no differences between groups. 4 patients died during the follow-up (2 FT, 2 ST) and 2 FT patients dropped out before the end of the study. After 16?weeks (T1), FT participants scored significant improvement in the SEIQoL-DW index, pain dyspnoea sleep disturbance and bowel symptoms. Conclusions This exploratory RCT provides evidence that no harm was experienced by SPCS for patients severely affected by neurodegenerative disorders. There was an improvement in quality of life and physical symptoms for neurological patients in palliative care. Caregiver burden was not affected by the service

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

BACKGROUND AND OBJECTIVES: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. METHODS: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score 64 3 and no comorbidities) by the \u3c72 test, and the risk excess was quantified by risk ratios (RRs). RESULTS: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). DISCUSSION: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB