B-cells, T-cells and inflammatory CSF biomarkers in primary progressive MS and relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) trial

Objective: To assess longitudinal changes in B cells, T cells, neurofilament light (NfL) and soluble inflammatory markers in patients with primary progressive (PPMS) and relapsing (RMS) multiple sclerosis following ocrelizumab (OCR) treatment. Background: OCR, an anti-CD20 molecule, reduces progression in MS. Less is known about biomarkers and mechanisms of anti-CD20 action in PPMS than in RMS. Presence of T1 gadolinium–enhancing lesions has been associated with higher baseline cerebrospinal fluid (CSF) NfL and serum NfL (sNfL) in PPMS and RMS and significant sNfL reductions in PPMS (ORATORIO trial, n=347; p Design/Methods: Twenty-eight patients with PPMS in OBOE received 600-mg OCR infusions every 24 weeks. CSF was collected at baseline and 52 weeks. Blood was collected at baseline and 6 postdose time points. Samples were assessed for NfL (Quanterix Advantage), CXCL13 and CCL19 (immunoassay) and CSF B and T cells (flow cytometry). Data were compared with previously reported RMS data. Results: Baseline CSF B cells, T cells and CCL19 levels were indistinguishable between patients with PPMS and RMS, while CSF NfL (p=0.012) and CXCL13 (p=0.020) were decreased in patients with PPMS. PPMS CSF B cells (n=15; median percent change, −100 [IQR −100, −91.4]; p Conclusions: Baseline CSF B cells, T cells and inflammatory biomarkers were similar in PPMS and RMS. In PPMS, similar to RMS, CSF B and T cells and CXCL13 were reduced following OCR treatment. Disclosure: Amit Bar-Or has participated as a speaker in meetings sponsored by, and received consulting fees from, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, Janssen/Actelion, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. Grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme.Dr. Bennett has received personal compensation from Alexion, Chugai, Clene Nanomedicine, Equillium, Frequency Therapeutics, Genentech, Roche, MedImmune/Viela Bio, Novartis. Dr. Bennett has received royalty, license fees, or contractual rights payments from Aquaporumab. Dr. Bennett has received research support from EMD Serono, Novartis.Dr. Von Budingen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of F. Hoffmann-La Roche Ltd. Dr. Carruthers has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, EMD Serono, Sanofi, Biogen, Novartis, and Teva. Dr. Carruthers has received research support from Teva Innovation Canada, Roche Canada and Vancouver Coastal Health Research Institute. Dr. Edwards has received research support from Genzyme.Dr. Fallis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD Serono. Dr. Fiore has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Gelfand has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Alexion, and Alkem Laboratory. Dr. Gelfand has received personal compensation in an editorial capacity for Dynamed Plus and Neurology Neuroimmunology and Neuroinflammation. Dr. Gelfand has received research support from Genentech and MedDay.Dr. Giacomini has nothing to disclose. Dr. Greenberg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Roche/Genentech, Celgene, EMD Serono, Novartis. Dr. Greenberg has received research support from CLENE Nanomedicine, Chugai, Medimmune.Dr. Hafler has nothing to disclose. Dr. Longbrake has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting fees from Alexion, Biogen, EMD Serono, Genentech, and Genzyme. Dr. Longbrake has received research support from received research support from the Nancy Davis Center Without Walls and NIH NINDS K23-NS107624..Dr. Assman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech Inc, and F. Hoffmann-La Roche Ltd.Dr. Ionete has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi. Dr. Ionete has received research support from Biogen, Roche, and Sanofi. Dr. Kaunzner has received research support from Biogen. Dr. Lock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen; Sanofi Genzyme; EMD Serono; InterX Inc; Diagnose Early. Dr. Ma has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Musch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Genentech, Inc., and a shareholder of F. Hoffmann-La Roche Ltd.. Dr. Pardo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, Celgene, EMD Serono, Roche/Genentech, Novartis, and Sanofi Genzyme.. Dr. Pei has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. fees for clinical trials (serving as Chair of data monitoring committee with Parexel). Research grants (Genzyme, Merck KGaA, and Novartis) and fees for clinical trials (serving as Chair of data monitoring committee with Parexel).Dr. Weber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with M. S. Weber received travel funding and/or speaker honoraria from Biogen-Idec, Merck Serono, Novartis, Roche, TEVA, Bayer and Genzyme.. Dr. Weber has received personal compensation in an editorial capacity for M.S.Weber serves as an editor for PLoS One. Dr. Weber has received research support from M. S. Weber receives research support from the Deutsche Forschungsgemeinschaft (DFG; WE 3547/5-1), from Novartis, TEVA, Biogen-Idec, Roche, Merck and the ProFutura Programm of the Universitatsmedizin Gottingen.. Consulting and/or speaking fees (Almirall, Bayer, Biogen, Merck, Novartis, Roche, Sanofi, and Teva) grant/research support (Biogen, Novartis, Sanofi, and Teva)Dr. Herman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Dr. Harp has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech. Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis and TG Therapeutics not outside of multi-center clinical trials