Impact of extended interval dosing of ocrelizumab on immunoglobulin levels in multiple sclerosis

Abstract

Long-term B cell depletion with ocrelizumab in multiple sclerosis (MS) is associated with severe side effects such as hypogammaglobulinemia and infections. Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing (EID) scheme. Immunoglobulin levels of 51 patients with ≥24months of treatment with ocrelizumab were analyzed. After ≥4 treatment cycles, patients chose to either continue on the standard interval dosing (SID) regimen (n= 14) or, in the case of clinically and radiologically stable disease, switch to B cell-adapted EID (n= 12, next dose at CD19+ Bcells >1% of peripheral blood lymphocytes). Levels of immunoglobulin M (IgM) declined rapidly under ocrelizumab treatment. Risk factors for IgM and IgA hypogammaglobulinemia were lower levels at baseline and more previous disease-modifying therapies. B cell-adapted EID of ocrelizumab increased the mean time until next infusion from 27.3 to 46.1weeks. Ig levels declined significantly in the SID group over 12months but not in the EID group. Previously stable patients remained stable under EID as measured by expanded disability status scale (EDSS), neurofilament light chain, timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT), symbol digit modalities test (SDMT), and multiple sclerosis impact scale (MSIS-29). In our pilot study, B cell-adapted EID of ocrelizumab prevented the decline of Ig levels without affecting disease activity in previously stable patients with MS. Based on these findings, we propose a new algorithm for long-term ocrelizumab treatment. This study was supported by the Deutsche Forschungsgemeinschaft (SFB CRC-TR-128, SFB 1080, and SFB CRC-1292) and the Hertie Foundation.