To determine whether extending rituximab dosing intervals to ≥12 months results in higher disease activity compared to standard intervals in persons with relapsing remitting multiple sclerosis (pwRRMS)

To determine the incidence of anti-NMDAR encephalitis in a large multi-ethnic patient cohort.

Objective: To estimate to what extent increased infection risk from more rituximab exposure is mediated by hypogammaglobulinemia in multiple sclerosis (MS) patients. Background: Prolonged treatment with B-cell depleting therapies increase the risk of hypogammaglobulinemia and infections. These relationships are poorly understood. Design/Methods: We conducted a retrospective cohort study utilizing the electronic medical record among Kaiser Permanente Southern California members who met MS diagnostic criteria and were treated with at least two rituximab infusions, 2008–2020. Multivariable Andersen-Gill hazards models were used to assess risk of recurrent outpatient (≥4/year) or serious/hospitalized infections and linear regression to examine correlates of IgG values. Results: We identified 2477 MS patients who were treated with rituximab for a median of 2.0 years (IQR=1.0–3.0). 405 patients (16.4%) developed recurrent outpatient infections, 153 (6.2%) serious infections and 249 (10.1%) IgG <700 mg/dL. Higher cumulative rituximab dose (>4g) was correlated with lower IgG levels (Beta=−57.0, p<0.0001, ref≤2g) and, in models mutually adjusted for hypogammaglobulinemia, both were independently associated with an increased risk of serious (>4g, aHR=1.57, 95%CI=1.08–2.28, p=.018; IgG<500, aHR=2.90, 95%CI=1.52–5.54, p=0.001) and outpatient infections (>4g, aHR=2.09, 95%CI=1.64–2.66, p<.0001; IgG<500 aHR=2.48, 95%CI=1.64–3.75, p<.0001; ref=IgG≥700). Mediation analyses showed that hypogammaglobulinemia accounted for 12.6% of serious infection risk associated with higher cumulative rituximab exposure but was not significant for outpatient infections. Other independent modifiable risk factors were advanced physical disability for serious infections (aHR=5.86, p<.0001), obesity (aHR=1.38, p=.0017) and chronic obstructive pulmonary disease (aHR=1.88, p=.0001) for outpatient infections. Black (16.6% of population) or Asian (2.8%) race or Hispanic (31.0%) ethnicity was correlated with significantly higher IgG levels (Betas=260.7, 252.7, 67.3, respectively, p's<.0001, ref=white) but had no independent influence on infection risks. Conclusions: Higher cumulative rituximab doses increase the risk of infections primarily via mechanisms independent of hypogammaglobulinemia. Important factors that influence these relationships include selected comorbidities, race and ethnicity, advanced physical disability, and age. Disclosure: An immediate family member of Dr. Langer-Gould has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of American Thoracic Society. The institution of Dr. Langer-Gould has received research support from PCORI. The institution of an immediate family member of Dr. Langer-Gould has received research support from PCORI, ARQ, NIH. Dr. Langer-Gould has a non-compensated relationship as a Voting Member with ICER CTAF Panel that is relevant to AAN interests or activities. Bonnie Li has nothing to disclose. Ms. Smith has nothing to disclose. Ms. Gonzales has nothing to disclose. Dr. Xu has nothing to disclose.

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. Disclosure: Dr. Iordanova has nothing to disclose. Ms. Smith has nothing to disclose. Ms. Gonzales has nothing to disclose. Dr. Lee has nothing to disclose. Bonnie Li has nothing to disclose. An immediate family member of Dr. Langer-Gould has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of American Thoracic Society. The institution of Dr. Langer-Gould has received research support from PCORI. The institution of an immediate family member of Dr. Langer-Gould has received research support from PCORI, ARQ, NIH. Dr. Langer-Gould has a non-compensated relationship as a Voting Member with ICER CTAF Panel that is relevant to AAN interests or activities.

PCORI identified multiple sclerosis (MS) as an important research topic.People with MS, clinicians, and others wanted to learn how different treatment strategies, aimed at changing specific symptoms or the overall course of MS, affect patients' symptoms and quality of life.To address this issue, PCORI launched an initiative in 2015 on Treatment of Multiple Sclerosis.The initiative funded this research project and others.

Monday, April 27April 14, 2020Free AccessImplementation of a Risk-Stratified Multiple Sclerosis Treatment Algorithm: Improved Quality and Affordability (2009)Annette Langer-Gould, Stephen C. Cheng, Jessica Smith, Bonnie Li, and Michael H. KanterAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.2009 Letters to the Editor

May 7, 2019April 9, 2019Free AccessSerious Infections in Two Large US and Swedish Rituximab-treated Multiple Sclerosis Cohorts (S26.007)Annette Langer-Gould, Jessica Smith, Fredrik Piehl, Bonnie Li, and Thomas FrisellAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.S26.007 Letters to the Editor