Extended dosage interval of B-cell therapy in multiple sclerosis

Introduction: Ocrelizumab is an anti-CD20 monoclonal antibody used in the treatment of multiple sclerosis (MS). Anti-CD20 therapy causes lysis of B-cells thereby immunosuppression. Safety concerns during the COVID-19 pandemic resulted in paused treatment, thereby prolonged treatment interval. Aims: The study aims are to investigate differences in disease activity, levels of neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), T-,B- and NK-cells, and their relation in patients treated with a regular six-month interval or extended dosage interval. Methods: We included patients with MS that were treated ≥12 months with ocrelizumab and with a regular (24 weeks) or delayed (>4 weeks) time interval. NFL and GFAP were measured with SIMOA™ (ng/L) prior to infusion with ocrelizumab. B-, T- and NK-cells were measured on a national validated flowcytometry (10-9/L). Confirmed progression of disability (CPD) was determined by worsening in neurostatus at 6-12 months after infusion. MRI progression was defined as new or enlarged T2-weighted or T1-weighted gadolinium-enhancing lesions. Results: We included 187 patients. 99 patients were treated with extended dosage interval and the average delay was 11.4 weeks (SD:6.2, range: 4-53 weeks). 88 patients were treated with regular dosage interval. NFL-levels were 10.0 (SD:8.2) and 7.6 (SD:3.3) in extended patients and regular scheduled patients, respectively (ns). GFAP-levels were 77.2 (SD:40.0) and 71.5 (SD:29.8) in extended patients and regular scheduled patients, respectively (ns). No correlations were found between NFL/GFAP and length of extended dosage interval. B-cell levels were 0.033 (SD:0.049) and 0.0037 (SD: 0.0072) in extended patients and regular scheduled patients, respectively (p<0.0001). No correlations were found between B-cells and levels of GFAP/NFL (ns). No differences were found when comparing levels of T- and NK-cells in the two groups. Conclusions: We found similar levels of NFL and GFAP in both groups. Levels of B-cells were higher in delayed patients but not related to levels of NFL and GFAP, suggesting early rise of B-cells, but similar levels of neuroaxonal damage despite extended dosage interval in MS patients treated with ocrelizumab. Clinical and MRI results are currently being collected and will also be presented at the conference. Extending dosage interval could be relevant in selected patients or on an individualized basis in the treatment of MS.