Ocrelizumab in Patients with Active Primary Progressive Multiple Sclerosis: Clinical Outcomes and Immune Markers of Treatment Response
Marina Boziki,
Christos Bakirtzis,
Styliani-Aggeliki Sintila,
Evangelia Kesidou,
Evdoxia Gounari,
Aliki Ioakimidou,
Vasiliki Tsavdaridou,
Lemonia Skoura,
Asimina Fylaktou,
Vasiliki Nikolaidou,
Maria Stangou,
Ioannis Nikolaidis,
Virginia Giantzi,
Eleni Karafoulidou,
Paschalis Theotokis,
Nikolaos Grigoriadis
Affiliations
Marina Boziki
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Christos Bakirtzis
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Styliani-Aggeliki Sintila
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Evangelia Kesidou
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Evdoxia Gounari
Microbiology Laboratory, Department of Immunology, AHEPA University Hospital, 54636 Thessaloniki, Greece
Aliki Ioakimidou
Microbiology Laboratory, Department of Immunology, AHEPA University Hospital, 54636 Thessaloniki, Greece
Vasiliki Tsavdaridou
Microbiology Laboratory, Department of Immunology, AHEPA University Hospital, 54636 Thessaloniki, Greece
Lemonia Skoura
Microbiology Laboratory, Department of Immunology, AHEPA University Hospital, 54636 Thessaloniki, Greece
Asimina Fylaktou
National Peripheral Histocompatibility Center, Immunology Department, Hippokration General Hospital, 54642 Thessaloniki, Greece
Vasiliki Nikolaidou
National Peripheral Histocompatibility Center, Immunology Department, Hippokration General Hospital, 54642 Thessaloniki, Greece
Maria Stangou
Department of Nephrology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece
Ioannis Nikolaidis
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Virginia Giantzi
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Eleni Karafoulidou
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Paschalis Theotokis
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Nikolaos Grigoriadis
Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece
Ocrelizumab is a B-cell-depleting monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) and active primary progressive MS (aPPMS). This prospective, uncontrolled, open-label, observational study aimed to assess the efficacy of ocrelizumab in patients with aPPMS and to dissect the clinical, radiological and laboratory attributes of treatment response. In total, 22 patients with aPPMS followed for 24 months were included. The primary efficacy outcome was the proportion of patients with optimal response at 24 months, defined as patients free of relapses, free of confirmed disability accumulation (CDA) and free of T1 Gd-enhancing lesions and new/enlarging T2 lesions on the brain and cervical MRI. In total, 14 (63.6%) patients and 13 patients (59.1%) were classified as responders at 12 and 24 months, respectively. Time exhibited a significant effect on mean absolute and normalized gray matter cerebellar volume (F = 4.342, p = 0.23 and F = 4.279, p = 0.024, respectively). Responders at 24 months exhibited reduced peripheral blood ((%) of CD19+ cells) plasmablasts compared to non-responders at the 6-month point estimate (7.69 ± 4.4 vs. 22.66 ± 7.19, respectively, p = 0.043). Response to ocrelizumab was linked to lower total and gray matter cerebellar volume loss over time. Reduced plasmablast depletion was linked for the first time to sub-optimal response to ocrelizumab in aPPMS.
