Multiple sclerosis and related disorders · 2020
Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review.
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Elsbernd Paul M, Hoffman William R, Carter Jonathan L, Wingerchuk Dean M
Аннотация
BACKGROUND: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD.
OBJECTIVE: To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale.
METHODS: This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management.
RESULTS: Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months.
CONCLUSIONS: Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.
OBJECTIVE: To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale.
METHODS: This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management.
RESULTS: Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months.
CONCLUSIONS: Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.