BMI influences CD20 kinetics in multiple sclerosis patients treated with ocrelizumab

Abstract

Objectives: Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20 antigen exposed on B cells surface. Kinetic of B-cells repopulation after depletion therapy shows high intra and inter-individual variability. The aim of this study was to explore the influence of Body Mass Index (BMI) on kinetic of B-cell repopulation after treatment with OCR and on treatment response. Methods: 108 Multiple Sclerosis (MS) patients were enrolled at the time of the first dose of OCR administration and prospectively evaluated. Clinical, instrumental activity and disability progression were analyzed. According to B cells count, patients were divided into two groups: with fast (FR) and with slow (SR) repopulation rate, respectively. Results: Significant reduction of disease activity was observed in all patients and a stabilization of disease was obtained in progressive patients. Patients with FR had higher BMI compared to patients with a SR (p<0.001). Contrariwise no correlation between repopulation rate and treatment effectiveness was disclosed. Conclusions: In a real world setting we confirmed the effectiveness of OCR in relapsing remitting and progressive patients; patients with higher BMI had a FR. This suggests considering BMI for administration schedule although further investigations with longer follow up could improve treatment protocol and patient selection. MethodsThis is a retrospective analysis on collected data from the Second Division of Neurology of the University of Campania "Luigi Vanvitelli" in Naples, Italy. We included all MS patients who started OCR treatment according to clinical practice between January 2017 and June 2019. MS course was defined as Relapsing Remitting (RR) or Progressive (including primary and secondary progressive) (Lublin, 2014).Demographic data [age, sex, BMI], MS history [MS onset date, age at onset, disease duration, number of relapses, MS course, relapses one year and two years before OCR treatment, disease activity at baseline considered as MRI activity (gadolinium enhancement) or clinical relapse at the time of therapy start, previous disease modifying

CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis

“…There was again evidence that baseline BMI was associated with CD19 re-population. For each increase in BMI of 5 units, the odds of having CD19 count above 1% of total lymphocyte count increased by 2.50 (95% confidence interval: 1.45-5.20; p=0.003) as suggested previously ( Kletzl et al, 2019 , Signoriello et al, 2020 ).…”

Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness

“…A recently published study observed a significant depletion of CD19 + cells after six months and one year of treatment, but an incomplete depletion was detected in 41.8% of patients and in 24% of patients a significant reappearance of this B cells (2%) has been achieved. ( 15 ) One of the factors that may be responsible for these variations in repopulation of CD19 + cells identified in this study is body mass index.…”

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

“…As found with rituximab, naive/mature B cell repopulation will coincide with CD19 repopulation [26,97] and would take a median 62-72 weeks after three [95% confidence interval (CI) = 59•7-73•0 weeks, n = 51] or four cycles (95% CI = 59•1-85•4, range = 27-175 weeks, n = 51), respectively [105]. Such levels would require monitoring, as there is marked variability in repopulation kinetics between individuals and is, in part, a product of the ocrelizumab fixed-dosing schedule, as it is clear that the intensity of B cell depletion and repopulation speed relates to the body mass index of the individual [106,107]. This suggests that dose-adjustment for weight may have some benefit, as currently used in the treatment of people with MS with oral cladribine [107].…”