The study highlights tocilizumab's potential benefits and safety, even during SARS-CoV-2 infection.
Giuseppe Salemi
A published case report of a women with myelin oligodendrocyte glycoprotein associated disease (MOGAD) revealed that treatment with tocilizumab may be an effective therapy for drug-resistant forms of the disease. The woman, who experienced progressive and cognitive worsening associated with white matter lesions mimicking leukodystrophy, showed improvement in cognitive performance, walking ability, and brainstem functions after switching to tocilizumab treatment.1
In the case study, a 56-year-old Caucasian woman presented with a history of recurrent episodes of visual loss, diplopia, and gait abnormality initially followed by a full recovery. A subsequent lumbar puncture and brain MRI with gadolinium administration revealed an absence of oligoclonal bands and bilateral demyelinating lesions of frontal, temporal, parietal white mater, and other lesions in the cerebellum, midbrain, at the level of the cerebellar peduncles, at the bulbar-medullary junction, and in the medulla at the level of D5.
Given the relapsing-remitting course, the patient was originally diagnosed with multiple sclerosis and started on interferon-beta-1a until July 2018, when she presented a new relapse characterized by diplopia and postural imbalance. The patient was then switched to natalizumab treatment until July 2019 when she presented with severe cognitive impairment and limb ataxia together with severe motor impairment. Following negative results of multi-focal leukoencephalopathy, a new brain MRI revealed confluent demyelinating lesions, further prompting a new diagnosis.
Led by Giuseppe Salemi, an associate professor at the University of Palermo, in Italy, the presence of anti-MOG antibodies in December 2019 and March 2020 ultimately confirmed a diagnosis of MOGAD. Subsequently, the patient underwent plasma exchange after steroid therapy failed, with no significant improvements observed. On a brain MRI, clinicians observed a widespread leukoencephalopathy pattern with a post-contrast T1-weighted imaging enhancement.
From 2020 to 2022, the patient was treated with rituximab, a common immunosuppressant; however, she began to experience sudden symptom worsening with spatial agnosia, prosopagnosia, and pseudobulbar syndrome. In February 2022, she began tocilizumab at a dose of 8 mg/kg every 4 weeks.
Overall, the therapy was considered well tolerated, with no adverse events (AEs) or life-threatening conditions seen. Despite briefly testing positive for SARS-CoV-2 in May 2022, the patient continued on a new course of tocilizumab, where she continued to show no clinical events or AEs until January 2023. In the last examination, clinicians detected a moderate recovery of cognitive function, indicated by Mini Mental State Exam scores of 15, and walking capacity, being the patient able to walk with bilateral assistance.
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In October 2022, a new MRI revealed reduction lesion load at the level of the middle cerebellar peduncle and right middle-superior frontal gyrus in the absence of gadolinium-positive lesions or new T2 lesions. A follow-up MRI conducted at the end of September 2023 reported no increase in lesion load. At the date of the last follow-up in October 2023, no new relapse or signs of disease progression were documented.
The study authors noted that, "In leukodystrophy-MOGAD, a differential diagnosis between MOGAD and leukodystrophy could be challenging. The confirmed presence of anti-MOG antibodies, especially if determinate by a cell-based assay, a history of recurrent optic neuritis, progressive cognitive and psychiatric manifestations, observation of spinal cord lesions, absence of positive familiar history, and genetic screening with negative results for leukodystrophies when necessary, is elements in favor of MOGAD. Moreover, our MRIs documented lesions of cortical regions and subcortical U-fibers, areas usually preserved in patients with leukodystrophies."
Tocilizumab was also found to be safety administered in the occurrence of a SARS-CoV-2 infection. The 8 mg/kg dose of the therapy used to treat COVID-19 pneumonia is the same administered to treat MOGAD. "Therefore, it appears evident that treatment with tocilizumab since it acts on a common target to the pathogenesis of COVID-19 and MOGAD, as suggested by an analogous previous case report, should not be stopped in case of SARS-CoV-2 infection and can be considered safe."