Severe NMOSD Disability Associated With Escalation to Rituximab, Study Shows

A recent retrospective cohort study showed that severe baseline disability was strongly associated with subsequent treatment escalation to rituximab from azathioprine or mycophenolate mofetil in Thai patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). These findings suggest that earlier identification of high-risk patients may facilitate more individualized treatment approaches and may help inform policy decisions in resource-limited health care settings.^1,2

Among 173 patients (escalation group, n = 35; nonescalation group, n = 138) included in the study, baseline disability differed between groups. Although median Expanded Disability Status Scale (EDSS) scores prior to initiation of first-line therapy were similar, patients who later required treatment escalation had a greater burden of baseline disability compared with those who did not (median EDSS, 4 [4–6] vs 4 [3–5]; P = .022). Additionally, severe baseline disability was more frequently observed among patients who underwent escalation to rituximab (45.7% vs 24.6%; P = .014).

“In Thai patients with AQP4-IgG–positive NMOSD managed under an escalation-based treatment paradigm, baseline severe disability (EDSS ≥6) was the strongest clinical factor associated with subsequent escalation to rituximab. This finding underscores the value of early and systematic functional assessment in identifying patients at higher risk of inadequate disease control with conventional immunosuppressive therapy,” senior author Saharat Aungsumart, PhD, MD, neurologist at the Neurological Institute of Thailand, and colleagues wrote.¹

The study, published in Multiple Sclerosis & Related Disorders, aimed to identify clinical factors associated with escalation from first-line maintenance therapy to rituximab in patient with AQP4-IgG-positive NMOSD treated at the Neurological Institute of Thailand between 2019 and 2024. Patients included in the analysis were aged 18 years or older and had received azathioprine or mycophenolate mofetil for at least 6 months during the study period, with follow-up continuing until treatment escalation or last clinical visit. Authors categorized patients into an escalation group if rituximab was initiated or a nonescalation group if first-line therapy was maintained.

READ MORE: Survey Reports Relapse Prevention as Key Driver of Treatment Preferences in NMOSD

In univariable logistic regression analysis, baseline severe disability was significantly associated with treatment escalation ([OR], 2.58; 95% CI, 1.19–5.56; P = .016). The neutrophil-to-lymphocyte ratio showed a borderline association with treatment escalation (OR, 1.16; 95% CI, 0.99–1.35; P = .050), while antinuclear antibody positivity was also associated with escalation in univariable analysis (OR, 4.65; 95% CI, 1.23–17.58; P = .023). In addition, age at disease onset of 50 years or older showed a trend toward association with escalation (OR, 2.12; 95% CI, 0.98–4.59; P = .056).

In multivariable logistic regression analysis, severe baseline disability was independently associated with escalation to rituximab (OR, 18.19; 95% CI, 2.22-148.95; P = .007). No other demographic, clinical, or laboratory variables remained statistically significant after adjustment, including age at disease onset of 50 years or older (OR, 0.42; 95% CI, 0.04-4.86; P = .48), neutrophil-to-lymphocyte ratio (OR, 1.16; 95% CI, 0.99-1.35; P = .050), and antinuclear antibody positivity (OR, 4.65; 95% CI, 0.67-32.09; P = .12).

Among patients who underwent escalation to rituximab, subgroup analyses were conducted based on the primary reason for escalation. In the relapse-related subgroup, baseline severe disability was not significantly associated with rituximab initiation in either univariable (OR, 1.64; 95% CI, 0.71–3.79; P = .243) or multivariable analyses (OR, 1.22; 95% CI, 0.40–3.71; P = .72). In contrast, in the subgroup of patients who escalated treatment because of adverse events, baseline severe disability was significantly associated with rituximab initiation in both univariable (OR, 5.90; 95% CI, 1.90–18.30; P = .002) and multivariable analyses (OR, 15.18; 95% CI, 1.72–133.31; P = .014).

“While treatment escalation decisions in this setting are influenced by healthcare policy and reimbursement constraints, baseline severe disability may serve as a pragmatic indicator to support risk stratification and individualized treatment planning in routine clinical practice,” Aungsumart et al. “These results provide real-world evidence that may inform future prospective studies and contribute to ongoing discussions regarding optimization of treatment strategies and potential refinement of national treatment policies for NMOSD in resource-limited settings.”

REFERENCES
1. Siripornmongkol C, Apiwattanakul M, Aungsumart S. Baseline severe disability as a predictor of treatment escalation to rituximab in AQP4-IgG-positive NMOSD patients: A retrospective cohort study. Mult Scler Relat Disord. 2026;107:107022. doi:10.1016/j.msard.2026.107022
2. Silva GD, Apóstolos-Pereira SL, Boaventura M, et al. Early rituximab versus escalating therapy in neuromyelitis optica: A cost and quality of life analysis. Mult Scler Relat Disord. 2024;92:106160. doi:10.1016/j.msard.2024.106160