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Inebilizumab Efficacy Unchanged With Prior Rituximab Use in NMOSD

Disease Spotlight | <b>Disease Spotlight: NMOSD</b>

Annualized attack rate was reduced to 0.08 attacks per year after the first administration of inebilizumab, similar to those who were not previously exposed to rituximab.

Findings from a post-hoc analysis of the N-MOmentum trial (NCT02200770) showed that treatment with inebilizumab (Uplizna; Horizon Therapeutics) remained efficacious among participants with anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD) who had been previously treated with rituximab (Rituxan; Genentech).1,2

Of 230 participants who were randomized and received at least 1 dose of inebilizumab or placebo, 17 were treated with rituximab before entering the study; of these, 13 received study drug and 4 received placebo. Adjudicated attacks, secondary efficacy outcomes, and treatment-emergent adverse events (TEAEs) were assessed by during the 6-month randomized controlled period and the open-label period.

Prior to the first dose of inebilizumab, the mean ARR of the cohort was 0.78 attacks/person-year, with 7 participants experiencing attacks within 6 months after a rituximab infusion. At the conclusion of the study, the ARR of the subgroup decreased to 0.08 after treatment with inebilizumab and was similar to the ARR of participants without prior rituximab use (0.10). In total, 1 of the 13 participants had an attack during the randomized controlled period (HR vs all placebo, 0.16 [95% CI, 0.02-1.20]; P = .07), while 2 additional participants experienced attacks during the open-label period (ARR, 0.08 [95% CI, 0.02-0.34]).

READ MORE: Outer Retinal Layer Thinning Non-Factor in Retinal Damage of AQP4-IgG NMOSD

"It is encouraging to see that in this analysis, none of the seven patients who experienced breakthrough attacks while previously being treated with rituximab went on to experience an attack while taking Uplizna," Eoin P. Flanagan, MB, BCh, neurologist, Mayo Clinic, and study author, said in a statement.1 “Although Uplizna and rituximab both target B cells, Uplizna targets a broader range of B cells, and may explain why patients in the study who had attacks while being treated with rituximab did not experience attacks with Uplizna."

Secondary outcomes, including change on Expanded Disability Status Scale (EDSS) scores, active MRI lesions, and number of NMOSD-related hospital stays, were generally similar regardless of prior rituximab use. During the randomized controlled period, 2 of the 13 participants (15%) with prior use of rituximab experienced worsening of EDSS scores, while 6 (46%) had active lesions on MRI, and 1 (8%) had a hospital stay related to NMOSD.

TEAEs associated with inebilizumab were reported by 9 of the 17 participants (53%) with prior rituximab use and 79 of 208 (38%) without prior rituximab use. Serious TEAEs related to inebilizumab were low in both groups, with just 2 participants (12%) in the prior rituximab group reporting urinary tract infection and cellulitis. Infusion-related reactions were similar between the 2 groups, occurring in both 12% in those with and those without prior use of rituximab.

Serious infections of at least grade 3 occurred in 3 participants (18%) with prior rituximab experience and 20 (10%) and 22 (11%) participants, respectively, without prior rituximab experience. Among them include nasopharyngitis, urinary tract infection, cellulitis, and perforated appendicitis, all occurring in 1 participant each in the prior rituximab group. Notably, investigators did not find any opportunistic infections or cases of progressive multifocal leukoencephalopathy, a complication of B-cell depleting therapies, in the 17 rituximab-experienced patients.

"Physicians who are considering transitioning their patients from rituximab to UPLIZNA are eager for evidence that this can be done safely and effectively," Kristina Patterson, MD, PhD, medical director, neuroimmunology, Horizon Therapeutics, said in a statement.1 "This analysis may suggest that appropriate patients can successfully transition from rituximab to UPLIZNA, which is particularly important for physicians who have been hesitant to transition patients to a different medicine because they don’t want to trigger an attack."

In June 2020, inebilizumab become the first and only B-cell-depleting humanized monoclonal antibody FDA-approved treatment for AQP4+ NMOSD. The decision was based on results from the original N-MOmentum study, which showed that treatment with the medication resulted in a reduced risk of NMOSD relapse by 77%.3

Rituximab was the first anti-CD20 therapy used in MS. It is a chimeric antibody, approved since 1997 for hematological and autoimmune disorders. However, it is not approved for use in the treatment of MS nor NMOSD, but is commonly prescribed as for off-label use.

REFERENCES
1. New analysis published in Multiple Sclerosis and Related Disorders supports the efficacy of Uplizna (inebilizumab-cdon) in patients previously treated with rituximab for neuromyelitis optica spectrum disorder (NMOSD). News release. Horizon Therapeutics. November 22, 2021. Accessed November 29, 2021. https://ir.horizontherapeutics.com/news-releases/news-release-details/new-analysis-published-multiple-sclerosis-and-related-disorders
2. Flanagan EP, Levy M, Katz E, et al. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum study. Mult Scler Relat Disor. Published online October 24, 2021. Doi:10.1016/j.msard.2021.103352
3. FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord. News release. FDA. June 11, 2020. Accessed November 29, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-rare-disease-affecting-optic-nerve-spinal-cord