Whilst hunting through the ECTRIMS 2020 meeting I came across this presentation. We have made a hypothesis that ocrelizumab may act as an immune reconstitution therapy with long term-benefit form a short term treatment cycle. We don’t have the data because we don’t have the trial. The manufacturers have little incentive to do such a trial and neuros probably dont want to tread on the manu
P0110. Modulation of cerebrospinal fluid immunoglobulins by ocrelizumab treatment
M. Weber et al.Background: Intrathecal production of immunoglobulin (Ig) and the presence of cerebrospinal fluid (CSF)–specific oligoclonal bands (OCBs) are hallmarks of multiple sclerosis (MS) that persist throughout the disease course and treatment. Objectives: To describe baseline (BL) correlations of CSF IgM and IgG production with CSF biomarkers and to assess the pharmacodynamic effects of ocrelizumab (OCR) treatment on these parameters in patients with relapsing MS (RMS) from the Ocrelizumab Biomarker Outcome Evaluation (OBOE) study (NCT02688985). Methods: Seventy-nine of 100 total patients with RMS had available BL CSF samples for assessment of IgG OCBs, IgG and IgM (measured at University Medical Center Göttingen), with demographic, MRI and clinical parameters representative of the total RMS population. CSF samples at either 12 (n=22), 24 (n=24) or 52 (n=17) weeks postdose and from a 12-week reference arm (no OCR; n=16) were assessed for longitudinal changes. Results: Median (interquartile range [IQR]) CSF levels at BL were as follows: IgG index, 0.79 (0.63–1.28); IgM index, 0.19 (0.11–0.33); CD3+ T cell number, 2.52 (0.80–5.61) cells/µL; CXCL13, 9.89 (3.91–31.50) pg/mL; CCL19, 47.95 (31.09–70.86) pg/mL; neurofilament light chain (NfL) 1280.0 (828.1–2968.9) pg/mL. At BL, IgG index and IgM index correlated moderately with levels of B cells (r=0.65, r=0.4 respectively), T cells (r=0.54, r=0.3 respectively) and CXCL13 (r=0.58, r=0.43 respectively), but not CCL19 or NfL. IgG index tended to decrease with OCR treatment and was significantly reduced by 52 weeks (n=17/79; median [IQR] change from BL −9.5% [−20.4% to −0.1%]; p<0.02) compared with stable levels in the reference arm. While IgG OCBs were detected at BL in all patients, IgG OCBs tended to decrease with OCR treatment, with three of 17 patients having no detectable IgG OCBs at 52 weeks. Reductions in IgM index were not observed with OCR treatment. Conclusions: Baseline CSF levels of B cells, T cells and CXCL13 correlated with IgG index and to a lesser degree IgM index in patients with RMS from the OBOE study. Significant reductions were observed in IgG index with OCR treatment, along with a trend toward reduced OCBs, with three patients showing no detectable OCBs. These data suggest that OCR impacts CSF Ig production, a hallmark of MS not previously thought to be affected by B-cell depletion therapy. These 1-year observations need to be confirmed with longer-term data and correlated with clinical response
Disclaimer: Please note that the opinions expressed here are those of author and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
See comments from Prof Freedman
“Sometimes Ig levels can fall below the level of detection in gels used to determine OCB. Therefore lack of detection with a low Index might not mean absence of banding. We have observed the same in our HSCT patients who, 3 years out had very low Ig levels and OCB no longer could be resolved”.