Effectiveness of Lower Rituximab Doses in Neuromyelitis Optica Spectrum Disorder: A Population-based Cohort Study
Radostina Iordanova1, Jessica Smith3, Edlin Gonzales3, Angus Lee1, Bonnie Li3, Annette Langer-Gould2
1Los Angeles Medical Center, Southern California Permanente Medical Group, 2Neurology, Los Angeles Medical Center, Southern California Permanente Medical Group, 3Research & Evaluation, Southern California Permanente Medical Group
Objective:
To describe effectiveness and safety outcomes in neuromyelitis optica spectrum disorder (NMOSD) patients treated with <4g of rituximab per year
Background:
Optimal dosing of rituximab for NMOSD has not been established. The most common published regimens are 4 grams or 3g/m2 annually in divided doses. 
Design/Methods:
We conducted a retrospective cohort study utilizing the electronic medical record among Kaiser Permanente Southern California members who met NMOSD diagnostic criteria and were treated with at least one rituximab infusion 1/1/2010-9/22/2022. 
Results:

We identified 116 NMOSD patients who were treated with a median annual dose of 2,077 milligrams of rituximab (IQR=1673-2710mg) for a median of 4.6 years (IQR=2.4-8.0). The majority (88%) were aquaporin-4 IgG seropositive. Fifty-eight (50%) patients received an induction dose of 1g or less. The most common initial rituximab maintenance dose was 1g every 6 months (n=80, 69%), with 22 (19%) receiving lower and 14 (12%) higher doses. Rituximab dosing was lowered in 34 (29%) and increased in 6 (5.2%) patients. Twenty-one (18%) relapsed following rituximab treatment, of which 7 occurred within 6 months of initiation. Patients who relapsed had similar demographic and clinical characteristics at rituximab initiation and there were no significant differences in induction, initial maintenance or median annual doses compared to relapse-free patients. Six patients (5.2%) died within 2 years of their most recent rituximab dose, 3 from advanced NMO and 1 from COVID-19 pneumonia. Rituximab was discontinued in 28 (24%) patients, 10 (8.6%) for infections, 5 relapses, 2 hypogammaglobulinemia, 2 infusion reactions and 2 for disease stability.

Conclusions:

We found that annual rituximab dose of ~2gm adequately controlled disease activity in >95% of NMOSD patients yet led to discontinuation from infections or hypogammaglobulinemia in 10.3% in this diverse, population-based cohort. Taken together with the existing literature, these findings indicate that even lower rituximab doses may result in an improved risk/benefit profile.

10.1212/WNL.0000000000202445