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Off-label and approved monoclonal antibodies are associated with a significantly lower risk of relapse compared to standard treatments. Off-label monoclonal antibodies can be utilized in resource-limited settings.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating condition involving the central nervous system (CNS). Both off-label and Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) are utilized in the prevention of MMOSD relapse. This systematic review and network meta-analysis evaluated the safety and efficacy of the two mAb groups in contrast to the current treatments.

The study concluded that off-label mAbs could be utilized as first-line therapy to improve clinical outcomes in NMOSD patients, such as annualized relapse rate (ARR), serious adverse events (SAEs), and disease relapse, in settings with limited access to FDA-approved mAbs. The study findings are published in the journal Frontiers in Neurology.

Characteristics of Included Studies

This systematic review and network meta-analysis included seven randomized controlled trials (RCTs) with 776 patients, the majority female. The mean age range was 32–45 years. 

Lower Risk of Relapse With FDA-Approved mAbs

The highest relapse-free survival rate was indicated in patients administered approved-mAbs, followed by off-label mAbs, and lastly, no treatment, which was associated with the worst relapse-free survival rate. The median time to relapse was recorded to be 25.8, 54.4, and > 55 months in the standard treatment, no-treatment, and mAbs treatment groups, respectively. Patients administered off-label and FDA-approved mAbs had 0.34-fold and 0.27-fold lower relapse rates, respectively, compared to patients in the no-treatment group.

Similarly, lower risk was also observed when mAbs were compared to the standard treatment group. According to the Surface Under the Cumulative Ranking (SUCRA) curve, the best treatment implicated in the reduction of relapse was FDA-approved mAbs with an 85.6 SUCRA, followed by the administration of off-label mAbs with a SUCRA of 68.2.  

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Comparing the Effectiveness of Approved and Off-Label Monoclonal Antibodies

The unstandardized mean difference (USMD) of post-treatment ARR was lower in the approved-mAbs and off-label mAbs compared to standard treatment and no-treatment groups. However, there were no significant differences in the mean post-treatment ARRs among approved and off-label mAbs.

Post-Treatment Changes in Expanded Disability Status Scale Score

Regarding post-treatment changes in the Expanded Disability Status Scale score, the USMD of FDA-approved mAbs was lower compared to standard treatment and no-treatment groups, whereas the USMD of off-label mAbs was higher compared to the comparators. None of these comparisons were statistically significant.

Serious Adverse Events in Monoclonal Antibody Therapy

The majority of the SAEs necessitated hospitalization of patients due to severe infections. The SAEs related to off-label and approved-mAbs were lower than for the comparators (no-treatment and standard treatment groups); however, the comparison was not statistically significant.

The study concluded that off-label and FDA-approved mAbs are associated with a significantly lower risk of relapse compared to standard treatments. Off-label mAbs can be preferred in resource-limited settings.


Aungsumart, S., Youngkong, S., Dejthevaporn, C., Chaikledkaew, U., Thadanipon, K., Tansawet, A., Khieukhajee, J., Attia, J., McKay, G. J., & Thakkinstian, A. (2023). Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis. Frontiers in Neurology, 14. https://doi.org/10.3389/fneur.2023.1166490