Presence of cytokines linked to NMOSD activity
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Key takeaways:
- There is limited information on cytokine levels in neromyelitis optica spectrum disorder.
- Cytokine levels in those with NMOSD were reduced, compared with baseline, after inebilizumab treatment.
Presence of cytokine proteins in those with neuromyelitis optica spectrum disorder was linked to disease activity, which was lessened after treatment with inebilizumab, according to a presentation from ECTRIMS 2023.
“Neuromyelitis optica spectrum disorder is a chronic, autoimmune disease characterized by recurrent attacks on the central nervous system causing permanent neurological damage and cumulative disability,” Sean J. Pittock, MD, director of Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology, and colleagues wrote. “Cytokine levels are known to be elevated in rheumatologic diseases, but there is limited information regarding these levels in NMOSD.”
Pittock and colleagues sought to evaluate the relationship between cytokine levels and disease activity in NMOSD patients from N-MOmentum, a randomized, double-blind, placebo-controlled study which was conducted in specialty clinics in 25 countries.
They analyzed protein biomarkers related to cytokine signaling and inflammatory processes from 211 individuals given either inebilizumab or placebo, via a multiplex immunoassay panel and biomarker panel. The Mann-Whitney U test with a 10% false discovery rate cutoff was used to identify dysregulated proteins. Cytokine profiles were also evaluated for correlation to longitudinal clinical endpoints such as attack rate, MRI findings, hospitalizations and disability throughout the study interval.
Results showed that protein measurements were dysregulated significantly in 18 of the 92 proteins measured.
In evaluating the association of baseline cytokines with disease activity, the researchers found a weak correlation of interleukin-6 with Expanded Disability Status Scale score at baseline, (R = 0.27, P > 0.0001) and the SF36 PCS, (R = -0.21, P = 0.002). High and low marker levels and evaluating for attack rate and new/enlarging T2 MRI findings over the course of the trial showed no difference for interleukin-6 while interleukin-17a and IFN- were associated with increased new T2 findings at higher levels.
Data further showed the attack rate decreased throughout the open-label portion of the study in the inebilizumab group, regardless of baseline cytokine levels.
"As expected, some patients showed striking elevation in certain immunologic biomarkers in particular IL-17a, IL6 and INF-gamma," Bruce A. Cree, MD, PhD, study co-author and professor of clinical neurology at the Weill Institute for Neurosciences at the University of California, San Francisco, told Healio in an email. "Importantly, inebilizumab was effective in suppressing NMOSD clinical attacks regardless of baseline cytokine profile."