Compared with placebo, inebilizumab-treated participants showed attenuated biomarker elevation during attacks and reduced biomarker levels over time in the absence of adjudicated attacks.
A recently published post-hoc analysis of the phase 3 N-MOmentum trial (NCT02200770) revealed that among relevant biomarkers, serum neurofilament light (NfL) at attack was the strongest predictor of disability worsening in patients with neuromyelitis optica spectrum disorder (NMOSD). Treatment with inebilizumab (Uplizna; Horizon), an FDA-approved therapy, was associated with lower levels of serum glial fibrillary acidic protein (GFAP) and sNfL than placebo.
"This analysis provides valuable insights into how we can improve care for people with NMOSD by integrating easily accessible serum biomarker assessments into treatment decision-making," Orhan Aktas, MD, professor in the Department of Neurology at Heinrich-Heine-University, said in a statement. "Conducting assessments of the sNfL biomarker during an attack can inform clinicians about the attack severity and the likelihood of residual disability in the patient, and therefore may guide therapeutic interventions to help preserve their long-term outcomes. Combination with other select serum biomarkers such as sGFAP may further increase prediction of clinical activity and, thus, prognosis in this devastating disorder."
N-MOmentum, the study which served as the basis for inebilizumab’s approval in 2020, randomized patients with NMOSD to receive either inebilizumab or placebo for 28 weeks, followed by a 2-year open-label phase. In the post-hoc analysis, sNfL, ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau), and GFAP were measured using single-molecular arrays in 1260 scheduled and attack-related samples from study participants and 2 control groups. At baseline, 198 of the 215 participants (92.1%) were aquaporin-4 (AQP4)-positive, 7 (3.3%) were seropositive for myelin oligodendrocyte glycoprotein-immunoglobin G (MOG+) and 10 (4.7%) had no detectable autoantibodies for AQP4 or MOG, considered double-negative.
Study results showed that biomarkers other than sGFAP do not add value in identifying or predicting attacks. Specifically, 37.5% of participants (3 of 8) without elevated sGFAP during an attack had elevated sNFL; sTau and sUCHL1 elevatations did not occur in the absence of increase sGFAP. Using logistic regression analysis, data showed that other non-sGFAP biomarkers had predictive capability that was either equal to or worse than the predictive capability of sGFAP alone in predicting attacks in AQP4+ participants.
A correlation analysis using 3 measures of disability from N-MOmentum revealed that sNfL correlated significantly with changes in ambulation subscale scores (Spearman R = 0.58; 95% CI, 0.24-0.92) and pyramidal functional system scores (Spearman R = 0.46; 95% CI, 0.12-0.80) of the Expanded Disability Status Scale Score (EDSS) during attack assessments. Compared with other biomarkers, sNfL was more sensitive for myelitis events but less sensitivie for optic neuritis events. Of the 4 biomarkers observed, sNfL was the strongest correlate of EDSS scores (Spearman R = 0.40; 95% CI, 0.06-0.74).
At the end of the double-blind treatment period, findings showed that fewer participants on inebilizumab had sNfL values above 16 pg/mL (22% vs 45%; OR, 0.36; 95% CI, 0.17-0.76; P = .004). In addition, inebilizumab-treated attack-free participants had significantly lower sNfL levels than attack-free participants who received placebo. Among those who experience an attack during the randomized controlled portion of the trial, sNfL levels were lower in inebilizumab-treated participants than those on placebo after 26 weeks (P = .03). Elevated levels of the other 3 biomarkers were observed at the time of attack, with sGFAP reaching statistical significance (P = .037).
"These findings support the strong clinical profile of UPLIZNA as a leading therapeutic option for NMOSD, with compelling evidence of its direct effects on critical biomarkers that signal disease activity and disability,” Kristina Patterson, MD, PhD, senior medical director, neuroimmunology medical affairs, Horizon, said in a statement. “The availability of these data in a rare and challenging disease like NMOSD can inform disease management strategies and contribute to improved outcomes for this population over time."