Ocrelizumab
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Lack of efficacy: case report An approximately 36-year-old man exhibited lack of efficacy during treatment with ocrelizumab for relapsing-remitting multiple sclerosis (RRMS). The man presented with an episode of numbness in the right arm and torso in April 2009. He developed intermittent lower extremity weakness in the following months, requiring bilateral assistance to ambulate. He had been diagnosed with RRMS in June 2010. His thoracic and cervical MRI showed diffuse cord T2 hyperintensity. A lumbar puncture (LP) revealed 17 oligoclonal bands. He received treatment with SC interferon beta-1a but the treatment was changed to cyclophosphamide after 3 months after requiring wheelchair assistance and developing bladder and bowel incontinence. While on cyclophosphamide, his brain MRIs revealed a small enhancing left corona radiata lesion and 8 new enhancing lesions. In October 2013, the treatment was changed to dimethyl fumarate. In September 2015, a brain MRI indcated new non-enhancing FLAIR hyperintensities. He then switched the treatment to ocrelizumab 300mg [route not stated] in October 2017. He received two 300mg doses 2 weeks apart and then received a 600mg maintenance dose in May 2018. His preinfusion serum CD19 concentration was 0.6% lymphocytes. He had next scheduled infusion in November 2018; however, one day before the infusion in November 2018, he experienced incoordination, difficulty concentrating, and exacerbated weakness. He received scheduled ocrelizumab infusion and the preinfusion serum CD19 concentration was 0.7% lymphocytes. He developed intermittent weakness in his left upper extremity in the following weeks (indicative of lack of efficacy of ocrelizumab). He further experienced generalised tonic-clonic seizures in the emergency department. He was therefore admitted. He was then sedated, and was intubated. Following caseation of the seizure activity and extubation, he was transferred to another institution. His neurologic examination showed ataxia with finger-nose-finger testing and increased weakness in the left upper extremity. An MRI revealed heterogeneous right parietal lobe hyperintensity, which exhibited peripheral enhancement on T1 sequences after gadolinium administration. Magnetic resonance (MR) perfusion imaging found decreased cerebral blood volume (CBV) in the area of interest. An LP found glucose 63 mg/dL, protein 81 mg/dL, 16 white cells and no red cells. His JC virus (JCV) PCR assay was negative. No malignant cells were detected. A stereotactic-guided brain biopsy of the lesion was done and the pathology was consistent with active demyelinating lesion. Immunohistochemistry study for polyoma virus was negative, excluding progressive multifocal leukoencephalopathy (PML). He then received treatment with methylprednisolone and methotrexate. Moreira Ferreira VF, et al. Tumefactive demyelination in a patient with relapsing-remitting MS on ocrelizumab. Neurology: Neuroimmunology and NeuroInflammation 6: 1-3, 803507246 No. 5, Sep 2019. Available from: URL: http://doi.org/10.1212/NXI.0
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