Effectiveness of rituximab versus oral immunosuppressive therapies in neuromyelitis optica spectrum disorder in a racially diverse cohort of subjects: A single-center retrospective study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune, inflammatory disorder characterized by severe relapses and high level of disability. In clinical trials of NMOSD, Black patients are under-represented, < 12%, compared to a relatively high prevalence of NMSOD in this population, 10/100,000. Despite the higher prevalence of NMOSD in Black and Asian patients, there is limited knowledge of the effectiveness of disease modifying treatments across racially diverse groups. OBJECTIVE: To assess the effectiveness of rituximab and oral immunosuppressive agents in a cohort of NMOSD patients, the majority of whom are Black, in a real-world, clinical setting. METHODS: A single-center retrospective study was conducted at the University of Chicago Medical Center. INCLUSION CRITERIA: (1) diagnosis according to the 2015 International Panel for NMO Diagnosis (IPND) Criteria, (2) positive anti-aquaporin-4 antibodies on ELISA or cell-based tests, (3) initiation of immunosuppressant therapy within 5 years of disease onset, (4) first-line treatment with rituximab, mycophenolate (MMF), or azathioprine (AZA). Patients with negative anti-AQP4 titers were excluded. Kaplan-Meier survival analysis was used to estimate proportion of relapse-free patients following initiation of first line immunosuppressive therapy. A Cox proportional hazards regression model assessed the association of risk of relapsing with first-line immunosuppressive treatments with and without adjustments of pre-specified factors (age at disease onset, duration of disease, sex, race, CNS location of relapse). RESULTS: 7 of 29 patients (24%) receiving rituximab experienced a relapse within the first 3 years of treatment vs. 13 of 23 patients (57%) receiving either AZA or MMF. Within the first 6 months of treatment, 2 (6.9%) patients treated with rituximab experienced a relapse vs. 7 (30.4%) patients treated with either MMF or AZA. In the 29 patients treated with rituximab, the 1-year and 3-year proportion of relapse-free patients was 88.8% and 70.9%. For the 23 patients treated with either AZA or MMF, the 1-year and 3-year proportion of relapse-free patients was 69.5% and 38.7%. In the univariate analysis, the risk of relapse was significantly higher in patients treated with AZA or MMF compared to those treated with rituximab (hazard ratio [HR] of 2.48 [0.99 - 6.21]; p = 0.046). CONCLUSION: In this real-world study involving a majority of Black NMOSD patients, rituximab was relatively more effective in preventing relapses within 3 years of therapy initiation than AZA and MMF. Rituximab remains an effective option for treating NMOSD, especially when there are delays in treatment due to access and economic issues associated with newer treatments.

Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations.

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present.

Estrogen hormone replacement therapy in incidental intracranial meningioma: a growth-rate analysis.

Incidental meningiomas (IMs) are the most common intracranial neoplasms, especially in perimenopausal women. There is ongoing debate on whether their incidence is increased by hormone replacement therapy. Meningiomas often express estrogen receptors, which were linked to higher proliferative activity according to some reports. Consequently, there is a theoretical risk of estrogen-based HRT (e-HRT) leading to an increase in tumor growth and thus altering the natural history of IMs. However, clinical data is lacking to support this notion. To identify differences in the natural history of IM after e-HRT exposure. We queried the NorthShore Meningioma Database for patients with ≥ 6 months of e-HRT. They were compared with age-matched IM controls. Forty patients were included in the e-HRT group (mean age 62.1 ± 12.0 years; mean duration of HRT 5.3 ± 4.5 years) and 80 in the no-HRT group (mean age 62.2 ± 12 years). Radiographic appearance was similar between groups. The average 2D tumor diameter was 35% lower in the e-HRT group (p = 0.02), with an absolute growth-rate of half of the no-HRT group (p = 0.02). Radiographic and clinical progression-free survival were 1.2 years and 3.3 years longer in the e-HRT group, respectively. These preliminary results suggest that e-HRT may be safe in incidental meningiomas.