A comparative study of tolerability and effects on immunoglobulin levels and CD19 cell counts with ocrelizumab vs low dose of rituximab in multiple sclerosis.

BACKGROUND: Rituximab (RTX) and ocrelizumab (OCR) are two anti-CD20 biologics used in MS; however, comparisons on safety and efficacy are rare. OBJECTIVE: To compare treatment outcomes over the first year with RTX and OCR. METHODS: Retrospective cohort study comprising MS patients initiating RTX at the Karolinska University Hospital (Sweden; n = 311) and OCR at Rocky Mountain MS Clinic (Utah, USA; n = 161), respectively. RESULTS: Levels of immunoglobulin G measured in blood dropped 0.16 g/L (95% confidence interval 0.01 to 0.31) with each OCR infusion, but remained stable with RTX. In contrast, levels of immunoglobulin M decreased to a similar extent with both drugs. Ten and 15% of patients discontinued treatment with RTX and OCR, respectively (n.s), however, adverse events leading to treatment discontinuation were more common with OCR (6.8% vs 2.6%; p = 0.026). Only 3.1 and 1.6% discontinued OCR and RTX, respectively, due to lack of effect (n.s). The degree of B cell depletion was superior with OCR. CONCLUSION: Overall, differences between the two treatments were small. Although the study design precludes robust conclusions regarding the risk-benefit with the studied therapies, our findings indicate that the tolerability and safety with RTX is not inferior to OCR.

Pharmacodynamics of natalizumab extended interval dosing in MS.

OBJECTIVE: To determine if the concentration and saturation of natalizumab (NTZ) administration at extended interval dosing (EID; every 5-8 weeks) over 18 months is able to be maintained in the range considered adequate to sustain the clinical efficacy of NTZ. METHODS: In a cross-sectional assessment of patients with multiple sclerosis (MS) who received standard interval dosing (every 4 weeks) or EID, serum NTZ concentrations were measured using ELISA, and α4-integrin receptor saturations were analyzed via cytometry, in blood samples obtained at trough timepoints. RESULTS: Trough serum concentration was above the "therapeutic" concentration of 2.0 µg/mL in 72% of EID patients. Trough saturation was above the "therapeutic" 50% threshold in 79% of EID-treated patients. Our model predicted that at least 9 NTZ infusions/year are required to maintain adequate trough saturation and concentration levels. Higher body mass index (BMI) was a predictor of suboptimal trough saturation on EID NTZ. CONCLUSIONS: Trough α4-integrin receptor saturation >50% correlated with high clinical efficacy of NTZ in previous studies. A continual treatment with EID maintains receptor saturation and concentration that are in the "therapeutic range" for most patients. This finding provides biological plausibility for the clinical efficacy of NTZ EID. Patients with higher BMI may require closer clinical and MRI follow-up.