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

Abstract

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.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

“…These medications are associated with an increased risk of infection and long-term use can be associated with an increased risk of hematologic and skin malignancies. • IL-6 targeting treatments (e.g., tocilizumab, satralizumab) -Small case series suggest tocilizumab might be highly effective in patients with MOGAD refractory to other immunosuppressive treatments (181,182). The drug is generally administered at a dose of 8 mg/Kg monthly, for a maximum recommended dose of 800 mg/month in adults.…”

Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications

“…Furthermore, there are different highly effective approved DMTs for NMOSD, including eculizumab, satralizumab, and inebilizumab [ 93 , 94 , 95 ]. In addition, other off-label therapeutics such as rituximab and tocilizumab have been used with success [ 96 , 97 ]. With respect to eculizumab, 94% patients were relapse-free in the extension study of the pivotal trial, even after more than 3.5 years [ 97 ].…”

“…In addition, other off-label therapeutics such as rituximab and tocilizumab have been used with success [ 96 , 97 ]. With respect to eculizumab, 94% patients were relapse-free in the extension study of the pivotal trial, even after more than 3.5 years [ 97 ]. However, this therapy in particular is extremely costly; hence, from a socioeconomic point of view and taking into account the burden on quality of life due to strictly required regular infusions, a possibly one-time stem-cell transplantation offers advantages [ 98 ].…”

Serum and Cerebrospinal Fluid Biomarkers in Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Associated Disease

“…The importance of studies on cytokines, and in particular interleukin-6 (IL-6), underlies the success of the recent randomized clinical trial on satralizumab, which was found to be more effective in AQP4-IgG NMOSD, but less effective for seronegative NMOSD ( 75 ). Similarly, tocilizumab was found to reduce the risk of relapses in both in AQP4-IgG NMOSD and MOGAD ( 76 , 77 ).…”