# Ravulizumab is Effective and Safe for Neuromyelitis Optica Spectrum Disorder Patients in Various Clinical Settings: A Single-Center Case Series with Concomitant Use of Rituximab

## TL;DR

Ravulizumab is shown to be effective and safe for treating NMOSD patients in various clinical situations, including during infections like COVID-19 and when switching from other biologics.

## Contribution

The study demonstrates the safe and effective use of ravulizumab in combination with rituximab and during transitions from other therapies.

## Key findings

- Ravulizumab effectively prevented relapses and was safe when used with rituximab for six months.
- Ravulizumab was successfully used in a patient with acute COVID-19 without increased infection risk.
- CH50 levels fluctuated but normalized after ravulizumab administration, suggesting timing affects monitoring accuracy.

## Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by inflammation of the optic nerves and spinal cord, often associated with anti-aquaporin-4 antibodies. Ravulizumab (RVZ), a monoclonal antibody targeting complement protein C5, has shown promise in reducing relapse rates and preventing neurological deterioration. However, studies reporting its use in specific clinical circumstances, such as switching from or to other biologics, or during infectious episodes such as COVID-19, are scarce.

This case series presents four patients with NMOSD treated with RVZ, highlighting its effectiveness and safety in diverse scenarios. Notably, two patients transitioned from satralizumab to RVZ without relapse or elevated infection risk, supporting RVZ as a viable alternative. However, persistent neurological symptoms affecting quality of life, despite relapse control, emphasize the need for more comprehensive care beyond relapse prevention. All four patients received concomitant RVZ and rituximab (RTX) for a duration of six months, during which no notable adverse events were recorded. Furthermore, neurological symptoms that had affected their quality of life were alleviated by RTX. One patient with acute COVID-19 was successfully managed with RVZ, demonstrating its potential role during infectious episodes.

The study also questions the reliability of serum 50% hemolytic complement (CH50) levels for monitoring RVZ efficacy. Fluctuations in CH50 were observed, but all values normalized shortly after RVZ administration, suggesting that the timing of blood collection affects the results. CH50 levels above the detection threshold were observed only in samples collected immediately before the next RVZ administration. Therefore, it was considered appropriate to use samples obtained shortly after RVZ administration to assess the efficacy of RVZ based on CH50 levels.

In conclusion, RVZ offers effective relapse prevention and versatility in NMOSD management, even in challenging clinical contexts. In some cases, administration of RVZ resulted in mild improvements in symptoms such as pain, stiffness, and numbness. The transition from RVZ to RTX was achieved safely without the use of corticosteroids, as no increase in adverse events such as infections, nor any rise in NMOSD relapses during the initial phase of RTX induction, was observed, even during six months of concomitant administration. Further studies are warranted to evaluate whether the relapse rate in patients who switched to RTX using this method is comparable to that in patients who initiated RTX in combination with conventional steroids. Additionally, research is needed to establish safe switching strategies from RVZ to other biologic agents such as satralizumab or inebilizumab.