Tocilizumab Effective in Patients With Inadequate Response to Intravenous Immunoglobulin for MOGAD

In patients with highly relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) who responded poorly to therapy with intravenous immunoglobulin (IVIG), tocilizumab (Actemra; Genetech) offered therapeutic benefits, suggesting the drug may be a viable alternative to IVIG.¹

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These results, published in Multiple Sclerosis and Related Disorders, highlight a potential new alternative for those who relapse with MOGAD. A considerable portion of MOGAD cases relapse, including those reported by Ramanathan et al.^1,2

Furthermore, there is a lack of a standardized treatment strategy to treat the disease, leading to clinicians adopting a wide range of therapeutic options extrapolated from another disorder, neuromyelitis optica spectrum disorder. IVIG has recently emerged as a promising therapy, but some patients experience relapses despite treatment, emphasizing the importance of investigating alternatives.^1,2

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor. It has demonstrated benefits in refractory patients with MOGAD in multiple case studies; importantly, in these case studies, the most prominent reason for initiating the drug was relapses. Despite this, there are limited reports focusing specifically on tocilizumab following relapses of IVIG.¹

The investigators sorted through 99 patients diagnosed with MOGAD at the National Cancer Center to find 9 that received at least a single dose of tocilizumab. They focused on patients who were treated with the drug for at least 6 months following a relapse while being treated with IVIG maintenance therapy. In total, they included 4 patients in the analysis.¹

All patients had received 2 or more immunotherapies prior to transitioning to tocilizumab. After originally being treated with a series of immunotherapies, such as rituximab, azathioprine, mycophenolate mofetil, and interferon-beta, all 4 patients eventually switched to maintenance therapy with IVIG at some point during their treatments.¹

IVIG was administered at a dose of 0.4/kg every 4 weeks. After a median of 2 relapses while on IVIG, the patients transitioned to tocilizumab; the median duration of IVIG maintenance was 21.9 months (range, 21.3-49.6 months). Median annualized relapse rate (ARR) on IVIG was 0.91 (range, 0.57-1.14), and the median ARR for any treatment prior to tocilizumab was 1.25 (range, 1.16-1.36).¹

The key result was that, following the initiation of tocilizumab therapy, all patients enrolled in the study remained relapse-free for a median follow-up duration of 25.0 months (range, 9.8-51.3). Importantly, there were no adverse events reported.¹

MOGAD has been shown to lead to substantial disabilities, especially after cumulative damage from recurrent attacks. Pache et al. and Duchow et al. documented several severe effects on patients with MOGAD. These include retinal neuro-axonal damage and visual impairment after optic neuritis, as well as distinctive disability progression associated with relapse, though Duchow et al. cautioned that this was less severe in MOGAD.^3,4

Both sets of authors cite these effects while emphasizing the need for “more efficacious treatment in MOGAD, especially for those with high disease activity.” These changes in treatment can include the timely initiation and close monitoring of immunosuppressive treatment, in addition to an early diagnosis.^1,3,4

The study authors noted that, although patient 1 was stable for 2 years with IVIG treatment, the remaining 3 patients experienced relapses within several months of treatment initiation. Unfortunately, a direct comparison between tocilizumab and IVIG is not possible due to the lack of controlled studies available, but “the successful application of tocilizumab in cases where IVIG has failed is noteworthy and merits further investigation.”¹

It was uncertain whether the dosage of IVIG impacted relapse in the patients. However, the investigators discussed the prolonged infusion time and significant expenses associated with high-dose IVIG treatment—and the lack of a standardized dosing protocol for MOGAD—in suggesting that tocilizumab may offer both practical advantages and therapeutic benefits.¹

REFERENCES

1. Kang YR, Kim KH, Hyun JW, et al. Efficacy of tocilizumab in highly relapsing MOGAD with an inadequate response to intravenous immunoglobulin therapy: a case series. Multiple Sclerosis & Related Disorders. 2024;91:105859. doi:10.1016/j.msard.2024.105859

2. Ramanathan S, Mohammad S, Tantsis E, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. Journal of Neurology, Neurosurgery & Psychiatry. 2018;89:127-137. doi:10.1136/jnnp-2017-316880

3. Pache F, Zimmermann H, Mikolajczak J, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation. 2016;13:282. doi:10.1186/s12974-016-0720-6

4. Duchow A, Bellmann-Strobl J, Friede T, et al. Time to disability milestones and annualized relapse rates in NMOSD and MOGAD. Annals of Neurology. 2023. doi:10.1002/ana.26858