L. Ramió I Torrentà
Neuroimmunology and Multiple Sclerosis Unit of Girona Neurology Department of Josep Trueta University HospitalAuthor Of 2 Presentations
PS01.05 - Rituximab treatment for MS: an observational multicentric dose comparison
Abstract
Background
Rituximab (RTX) is an anti-CD20 monoclonal antibody, widely used as an off-label treatment for multiple sclerosis (MS). Despite well-known efficacy and safety, RTX regimen has not yet been standardized.
Objectives
We aimed to compare efficacy and safety data of two different rituximab doses at two large Catalan multiple sclerosis centres.
Methods
A two-centre ambispective study considering all MS patients that have received at least one RTX cycle until February 2020 was conducted. In Barcelona centre (BC), RTX regimen used was 2g intravenously (IV), at least during 3 cycles, followed by 1g every 6 months, while in Girona centre (GC), was 2g IV, at least the first cycle, followed by 500mg every 6 months. Patients were clinically followed every 6 months with lab tests, and brain MRI scans were performed at baseline and yearly thereafter. Baseline clinical, radiological and demographic characteristics were collected. Annual relapse rate (ARR), contrast-enhancing lesions (CELs) and new T2 lesions at one and third year on treatment, as well as EDSS changes at last follow-up visit, were evaluated. Also, the dynamics of CD19% lymphocytes and IG immunoglobulin (IgG) values in serum, as well as the incidence of adverse events (AE) were described.
Results
A total of 303 patients (249 at BC and 54 at GC) were included. Main reason to start RTX was clinical progression plus inflammatory activity (clinical, radiological or both) (45.8% BC vs 79.6% GC). No differences on age at RTX onset, gender and disease duration were found between both centres. At baseline, mean ARR was 0.37±0.6 (BC) vs. 0.33±0.5 (GC); median EDSS was 5.5 (1-9.0) (BC) vs. 6.0 (1-8.0) (GC); and proportion of MRI with CELs was 32.4% (BC) vs. 42.6% (GC). ARR decrease to 0.05 (87.5%, p<0.001) for BC vs. 0.03 (90.3%, p=0.018) for GC at first year, and to 0.08 (88.3%, p=0.016) vs. 0 (100%, p=0.172) at third year. Considering only progressive MS phenotypes, 79.4% vs. 71.4% of patients remained stable or improved the EDSS. Regarding MRI findings, percentages of patients with CELs and new T2 lesions (BC vs GC) were 2.7% vs. 8% and 19% vs. 16% at one year; and 0% vs. 0% and 12% vs. 0% at third year. AE incidence was higher at BC during the first year (14.8% vs 4.1%). No difference in the dynamics of CD19% lymphocytes was found, while IgG values decreased significantly in the BC cohort throughout the first 3 years.
Conclusions
In the treatment of multiple sclerosis, low doses of rituximab seem to offer similar effectiveness with better safety profile than high doses.
PS09.03 - Predictive biomarkers of the development of autoimmunity in patients treated with alemtuzumab
Abstract
Background
Alemtuzumab has proven to be an effective treatment for patients with highly active multiple sclerosis (MS). However, its use has been limited by adverse events (AEs) as secondary autoimmunity, being the most frequent those involving the thyroid gland, observed in around 40% of patients.
Objectives
To explore whether patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity.
Methods
A multicentre prospective longitudinal study was performed, including fifty‐four Relapsing-Remitting MS (RRMS) patients diagnosed in five Spanish hospitals. Patient blood samples were collected before initiating treatment with alemtuzumab. Autoimmune AEs were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia and/or autoimmune nephropathy. Differences were assessed using Man-Whitney U tests. Cut-off values were established using ROC curves to predict autoimmune AEs. Odds ratios were calculated by Fisher tests.
Results
Fifty‐four RRMS patients, 36 (66.7%) women, with a median (range) age of 28 (13–67) years and median (range) follow-up of 6 (0-20) years. Fourteen patients (25.9%) experienced autoimmune AEs, and all of them were dysthyroidism. No immune thrombocytopenia or nephropathies were observed. No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune AEs and those who did not. Patients who experienced autoimmune AEs before treatment onset had a higher percentage of blood CD19+ B cells (p=0.001), with a higher relative percentage of naïve B cells and plasmablasts. When explored total cell numbers, only plasmablast levels remained significant (p=0.02). A lower risk of autoimmune AEs after alemtuzumab was observed among patients with less than 7.6% of blood CD19+ B cells [odds ratio (OR) 16, confidence interval (CI) 3.86–58.95, p<0.0001] or less than 0.13% of plasmablast cells [OR 9.33, CI 2.17–42.65, p=0.002].
Conclusions
A low percentages of blood CD19+ B cells or plasmablasts before Alemtuzumab treatment predicted a lower risk of autoimmune AEs.