Progressive Multifocal Leukoencephalopathy during Tocilizumab Treatment for Rheumatoid Arthritis

Abstract

A 61-year-old woman was diagnosed with rheumatoid arthritis 12 years ago and received multiple treatment regimens before achieving symptomatic stability with methotrexate plus tocilizumab, a humanized monoclonal antibody against the IL-6 receptor, about 2 years prior to the current presentation. Sixteen months after tocilizumab initiation, she exhibited dysarthria and disorientation; five months later, she was hospitalized with movement difficulties. Her neurological symptoms deteriorated thereafter, accompanied by enlarged cerebral white matter lesions on magnetic resonance imaging. A biopsy of the right frontal lesion confirmed progressive multifocal leukoencephalopathy (PML). While several therapeutic monoclonal antibodies have been linked to PML, this is the first case associated with tocilizumab.

Role of IL-6 in the commitment of T cell subsets

“…In a mouse model of west nile virus (WNV) infection, IL-17A-deficient mice show diminished cytotoxic CD8 + T cell responses that can be rescued by application of recombinant IL-17A as late as 6 days after infection [71] . Interestingly, IL-6 dependent T cell responses might also be relevant for proper immune surveillance of the central nervous system in humans as a case of progressive multifocal leukencephalopathy, a lytic infection of oligodendrocytes with JC virus, has recently been reported in a patient that was treated with an antibody to IL-6Rα for rheumatoid arthritis [72] . On the other hand, antigen-specific Th17 responses in Theiler virus infection increase the resistance of infected cells to cytotoxic CD8 + T cell responses and prevent clearance of the virus resulting in chronic demyelination [73] .…”

John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis

“…For instance, PML has been associated with chemotherapy-induced lymphocytopenia in solid tumors and it has been recorded in a case with follicular lymphoma treated with anti-CD20 monoclonal antibodies, and another spontaneous report was on a patient undergoing treatment for advanced ductal breast carcinoma and systemic sclerosis who developed the disease, whereas it has been discussed that atypical findings should not exclude diagnosis in cases that are not likely to have classical PML [49][50][51][52]. PML has been documented in people with various autoimmune-supposed conditions-apart from MS-who follow immunomodulation therapy, like Systemic Lupus Erythematosus (SLE) in parallel with cancer complications or not, Rheumatoid Arthritis (RA), ANCA-associated vasculitis, autoimmune hepatitis, myositis, ulcerative colitis, lupus nephritis, ankylosing spondylitis and Crohn's disease [53][54][55][56][57][58][59][60][61][62]. Also, PML has possibly been evident in a case with Coronavirus Disease 2019 (COVID-19) as well as in a patient with Hepatitis B virus-induced CD4 lymphocytopenia, while the disease may occur in the context of systemic sarcoidosis without immunosuppression in which it can even be the first sign, and it can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis [63][64][65].…”

Docking and Molecular Dynamics Study to Identify Novel Phytobiologics from Dracaena trifasciata against Metabolic Reprogramming in Rheumatoid Arthritis

“…The existing medications against RA, on more than one occasion, have produced undesirable fallouts [ 15 ]. Moreover, the existing biological therapy against the disorder bears financial restraints.…”