What is the optimal long‑term maintenance strategy for a young African‑American woman with aquaporin‑4 IgG‑positive neuromyelitis optica spectrum disorder refractory to rituximab, cyclophosphamide and ofatumumab, now stable on intravenous tocilizumab (Actemra) with steroid‑free status, residual spastic paraparesis managed with baclofen and gabapentin, type 2 diabetes mellitus, obesity, and anemia?

Optimal Long-Term Maintenance Strategy for Refractory AQP4-IgG+ NMOSD

Continue intravenous tocilizumab at the current regimen (4 mg/kg every 4 weeks) as the primary maintenance therapy, given the patient's documented 7+ years of clinical and radiographic stability, steroid-free disease control, and failure/intolerance of all B-cell-directed therapies. 1, 2

Rationale for Tocilizumab Continuation

• Tocilizumab represents the only effective therapy in this patient after documented failure of rituximab (allergic reaction), cyclophosphamide (inadequate control, infections), and ofatumumab (relapses, infections), making it the definitive maintenance choice. 1

• IL-6 receptor blockade addresses a distinct pathogenic mechanism from B-cell depletion—specifically targeting plasmablast survival, AQP4-IgG production, blood-brain barrier disruption, and Th17-mediated inflammation—which explains efficacy when rituximab fails. 1, 2

• The patient achieved complete steroid discontinuation under tocilizumab, eliminating long-term corticosteroid-related morbidity (critical given her comorbid type 2 diabetes and obesity). 1

• Real-world evidence demonstrates that 25-66% of NMOSD patients relapse even on rituximab, and this patient falls into that refractory subset requiring alternative immunosuppression. 1, 3, 4

Alternative Considerations (Lower Priority)

While newer FDA-approved agents exist for AQP4-IgG+ NMOSD, switching from a stable regimen carries risk:

• Eculizumab (anti-C5 complement inhibitor) achieves >95% relapse-free rates in AQP4-IgG+ NMOSD and is FDA-approved, but switching from a stable 7-year tocilizumab regimen introduces unnecessary risk of breakthrough disease. 2, 5

• Inebilizumab (anti-CD19) and satralizumab (anti-IL-6) are approved alternatives, but again, transitioning from documented long-term stability on tocilizumab is not justified without treatment failure. 2

• One case report documents successful eculizumab use after rituximab failure in AQP4-seronegative NMOSD, but this patient is AQP4-positive and already stable on tocilizumab. 5

Management of Comorbidities and Complications

Residual Neurological Deficits

• Continue baclofen and gabapentin for spastic paraparesis and sensory deficits; add physical therapy to maintain functional mobility and prevent contractures. 1

• Maintain desmopressin and oxybutynin for neurogenic bladder management; monitor for urinary tract infections given her history of recurrent UTIs. 1

Metabolic Comorbidities

• Continue GLP-1 receptor agonist for type 2 diabetes and obesity management, which has achieved good glycemic control and weight loss—critical for reducing cardiovascular risk and improving overall prognosis. 1

• Address the documented anemia (hemoglobin 9.1 g/dL) with iron studies, B12/folate levels, and reticulocyte count to determine etiology (chronic disease vs. nutritional vs. medication-related); consider erythropoietin if anemia of chronic inflammation. 1

Infection Risk Monitoring

• Implement meningococcal vaccination (required before eculizumab but prudent for any complement-pathway-related therapy consideration), pneumococcal vaccination, and annual influenza vaccination. 5

• Monitor for serious infections at each infusion visit; the patient's history of recurrent UTIs, staphylococcal infection, pressure sores, and COVID-19 pneumonia necessitates vigilant infectious disease surveillance. 1

• Check immunoglobulin levels annually; tocilizumab does not typically cause hypogammaglobulinemia (unlike rituximab, which causes IgG hypogammaglobulinemia in 17% of patients after median 5.4 years), but prior rituximab/cyclophosphamide exposure warrants monitoring. 4

Monitoring Protocol for Long-Term Tocilizumab

• Obtain serial spinal MRI every 6-12 months to document continued absence of new enhancing lesions or disease progression. 1, 2

• Monitor EDSS scores at each visit to objectively track disability progression or improvement; this patient's residual deficits require standardized assessment. 1, 2

• Check complete blood count, comprehensive metabolic panel, and liver function tests before each infusion to detect cytopenias, hepatotoxicity, or metabolic derangements. 1

• Monitor AQP4-IgG antibody titers periodically (every 6-12 months); antibody clearance correlates with durable disease remission and treatment response. 2

Critical Pitfalls to Avoid

• Do not switch to rituximab or other B-cell-depleting therapy given documented allergic infusion reaction to rituximab and failure of ofatumumab. 1, 4

• Do not discontinue tocilizumab prematurely; relapses occur in 50-60% of NMOSD patients during immunosuppression taper, and this patient has already demonstrated refractory disease. 1, 2

• Do not restart chronic corticosteroids; the patient achieved steroid-free status, and reintroducing prednisone would worsen diabetes, obesity, and infection risk. 1

• Do not delay treatment of acute relapses if they occur; initiate high-dose IV methylprednisolone (1000 mg/day for 3-5 days) immediately, followed by plasma exchange if steroid-refractory, as treatment delay beyond 2 weeks worsens outcomes. 1, 2

Multidisciplinary Care Coordination

• Maintain rheumatology involvement for biologic infusion monitoring, immunosuppression-related complication management, and metabolic comorbidity oversight. 1

• Coordinate with neurology for NMOSD-specific disease monitoring, MRI surveillance, and acute relapse management. 1, 2

• Engage physical medicine and rehabilitation for spasticity management, mobility optimization, and prevention of secondary complications (pressure sores, contractures). 1

• Involve urology or continence specialists for neurogenic bladder management and recurrent UTI prevention strategies. 1