Author Of 1 Presentation
P0686 - Aquaporin-4 antibody seroreversion in patients with neuromyelitis optica spectrum disorder treated with rituximab. (ID 1883)
The mechanism of action (MOA) of anti B-cell therapies in CNS demyelinating disorders associated with Aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorders (NMOSD) is unknown. Restoration of immune tolerance by blocking self-antigen presentation by autoreactive B to T cells and return to immune homeostasis has been postulated as a MOA.
Presence of AQP4-Ab is a marker of breakdown of immune tolerance in NMOSD while their disappearance after initial positivity could signify restoration of immune homeostasis. The outcome of AQP4-Ab in NMOSD treated with rituximab has not previously been examined.
To examine the evolution of AQP4-Ab status in a cohort of patients with CNS demyelinating disorders that were treated with rituximab.
Retrospective study of consecutive patients with recurrent optic neuritis or transverse myelitis treated with rituximab between 2006 and 2020. The data on AQP4-Ab status were obtained by chart review.
A total of 51 patients who were on long-term monotherapy with rituximab 1 gm IV every 6 months were identified. All were clinically stable. All serology was obtained by commercial laboratories as reported in the respective clinical records. Twenty-nine patients were AQP4-Ab positive (57%) at some time using the ELISA or more recently, the cell-based assay. In 23 patients re-testing for serological status was undertaken at varied intervals. Serostatus changed in 10 patients with 4 patients previously seronegative now becoming seropositive, and 6 patients who were seropositive becoming seronegative. In some subjects where seroreversion occurred, when titers were reported, a decrease in titer over time occurred before becoming seronegative.
AQP4-Ab reactive status can revert to non-reactivity on rituximab therapy in some patients. The seroconversion, however, was not a marker for response to rituximab as a favorable clinical response was also observed in persistently seropositive patients as well. This previously unrecognized observation suggests that the change in AQP4-Ab status from positive to negative on rituximab therapy can be used as a potential marker to guide future randomized discontinuation trials of rituximab in a select group of clinically stable patients.