Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review

Carter, Jonathan L; Hoffman, William; Carter, Jonathan L.; Wingerchuk, Dean M.

doi:10.1016/j.msard.2020.102696

Cited by 55 publications

(33 citation statements)

References 32 publications

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“…Our findings are in line with those of a recent study, which showed that TCZ therapy was associated with clinical and radiographic relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids in a cohort of 10 patients with MOGAD over an average treatment duration of 28.6 months. 33 Overall, when considering disease activity, including ARR, as well as suspected side effects during TCZ therapy, we did not observe a clear advantage of add-on treatments, supporting the use of TCZ as monotherapy.…”

Section: Discussionmentioning

confidence: 53%

“…13,14 As AQP4-IgG+ NMOSD and MOGAD both display antibody-and complement-mediated CNS injury and similar inflammatory CSF profiles (with elevated IL-6), 27,28 IL6-blockade may also be beneficial in MOGAD, supported by recent case reports. 23,25,26,[29][30][31][32][33] This retrospective multicenter study explored the safety and efficacy of TCZ in patients with MOGAD and is able to connect these findings with the effects of TCZ in classical (i.e., AQP4-IgG+) or double-seronegative NMOSD.…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

Ringelstein

Ayzenberg

Lindenblatt

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesTo evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD).MethodsAnnualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab.ResultsPatients received TCZ for 23.8 months (median; interquartile range 13.0–51.1 months), with an IV dose of 8.0 mg/kg (median; range 6–12 mg/kg) every 31.6 days (mean; range 26–44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5–5) to 0 (range 0–0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0–5] to 0 [range 0–4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0–3.0] to 0.2 [range 0–2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy.DiscussionThis study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

Ringelstein

Ayzenberg

Lindenblatt

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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“…Another antibody-mediated autoimmune disease of the central nervous system, i.e. anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD), also appears to be responsive to anti-IL-6Rα antibody treatment [88] .…”

Section: Il-6 In T Cell-mediated Autoimmunitymentioning

confidence: 99%

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

Korn

Hiltensperger

2021

Cytokine

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“…Case series data indicate that CD20 B cell depletion can be effective in MOGAD; however, refractory cases occur more frequently than in AQP4 NMO and relapses can be seen in up to 50% of patients (n = 121) despite efficient B cell depletion [124,145,146]. Anti-IL-6 therapy with tocilizumab in small case series of 3 and 10 patients has shown that treated patients remained relapsefree for an average of 23 to 28 months [139,147]. Common side effects included neutropenia, low platelet count, and liver enzyme elevations apart from infections (https:// www.…”

Section: Myelin Oligodendrocyte Glycoprotein Antibody-related Diseasementioning

confidence: 99%

Evolution of Anti-B Cell Therapeutics in Autoimmune Neurological Diseases

Stathopoulos

Dalakas

2022

Neurotherapeutics

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B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antigen-presenting cells facilitating antibody production but also as sensors, coordinators, and regulators of the immune response. In particular, B cells can regulate the T cell activation process through their participation in antigen presentation, production of proinflammatory cytokines (bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such an important interplay between B and T cells makes therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B cell therapies using monoclonal antibodies against B cell surface molecules have evolved into a rational approach for successfully treating autoimmune neurological disorders, even when T cells seem to be the main effector cells. The paper summarizes basic aspects of B cell biology, discusses the roles of B cells in neurological autoimmunities, and highlights how the currently available or under development anti-B cell therapeutics exert their action in the wide spectrum and immunologically diverse neurological disorders. The efficacy of the various anti-B cell therapies and practical issues on induction and maintenance therapy is specifically detailed for the treatment of patients with multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis and hyperexcitability CNS disorders, autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies. The success of anti-B cell therapies in inducing long-term remission in IgG4 neuroautoimmunities is also highlighted pointing out potential biomarkers for follow-up infusions.

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Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review

Cited by 55 publications

References 32 publications

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG–Associated Disease and Neuromyelitis Optica Spectrum Disorders

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

Evolution of Anti-B Cell Therapeutics in Autoimmune Neurological Diseases

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