Effects of BMI on B-Cells in Ocrelizumab-Treated Multiple Sclerosis

Real-world data published in Multiple Sclerosis and Related Disorders confirmed the effectiveness of ocrelizumab in relapsing-remitting and progressive multiple sclerosis (MS) and revealed that body mass index (BMI) has a significant influence on B-cell repopulation.

Ocrelizumab, a monoclonal antibody targeting the CD20 antigen on B-cells’ surfaces, was approved as treatment for relapsing and progressive MS. While ocrelizumab causes depletion of CD20+ cells and lymphocytes, there are limited data on factors influencing their repopulation and hence, the efficacy of treatment.

The goal of the current study was to assess the effectiveness of ocrelizumab in a real-world cohort of patients with MS and the influence of BMI on kinetic B-cell repopulation and response to therapy.

The study cohort enrolled 108 patients (mean age, 44.5 years, 55.5% women) at the time of the first dose of ocrelizumab, including 34 patients with relapsing-remitting MS, 55 patients with secondary progressive disease, and 19 patients with primary progressive disease.

Before each infusion of ocrelizumab, clinical and instrumental evaluations were performed in addition to blood samples. According to B-cell count, patients were separated into two groups: with fast repopulation (FR) and with slow repopulation (SR) rate, based respectively on whether CD19 reappeared or not at a 6-month follow-up.

The results confirmed the effectiveness of ocrelizumab in patients with relapsing-remitting MS as there was a significant 89% reduction of annualized relapse rate (0.55 pretherapy vs 0.06 posttherapy, P=.002), a 16% reduction of expanded disability status scale (EDSS) score (2.19 baseline vs 1.84 after 1 year; P=.032), as well as significant reduction of active lesions at 6 months (1.09 vs 0.23, respectively; P =.009) and 1 year (1.09 vs 0.00, respectively; P =.001).

Overall, the treatment in progressive patients had a positive effect on disease activity, with reduction of annualized relapse rate and active lesions on imaging. Furthermore, there was a nonsignificant reduction trend on Timed 25 foot walk Test (T25FW), and a mild stabilization of 9-HolePEG Test.

Analyzing baseline factors that may influence B-cell repopulations, including age at initiation of ocrelizumab treatment, disease duration, age at diagnosis, basal lymphocytes, and BMI, revealed that only the latter had a significant affect after 6 months. Patients with FR had higher BMI, compared to subjects with a lower BMI (mean BMI, 25.8 kg/m² in patients with FR with23.6 kg/m² in those with SR; P=.03).

The researchers found no correlation between repopulation rate and treatment effectiveness. In addition, they found that ocrelizumab had a favorable safety profile, as only 22 adverse events were documented.

The researchers acknowledged several study limitations, including the short follow-up, small sample size, observational and retrospective design, and the absence of standardized MRI procedures.

“This finding requires confirmation in large and longer studies and could be helpful in clinical practice to personalize treatment dose and to verify whether CD19 depletion could be used as biomarker to monitor disease activity and treatment efficacy,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Signoriello E, Bonavita S, Di Pietro A, et al. BMI influences CD20 kinetics in multiple sclerosis patients treated with ocrelizumab [published online 2020 May 17]. Mult Scler Relat Disord. doi:10.1016/j.msard.2020.102186