Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. OBJECTIVE: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). METHODS: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. RESULTS: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33). CONCLUSION: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.

Intravenous immunoglobulin treatment for acute attacks in myelin oligodendrocyte glycoprotein antibody disease.

BACKGROUND: The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. OBJECTIVE: The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. METHODS: A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. RESULTS: Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) (n = 8), multifocal (n = 7), TM (n = 3), brainstem (n = 1), and other encephalitis (n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation (p < 0.0001 for both outcome measures). CONCLUSION: IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results.

Predictors of relapsing disease course following index event in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disease that can present as a monophasic or relapsing disease course. Here, we investigate the predictors of developing relapsing disease with a focus on the index event. METHODS: MOGAD patients followed at Massachusetts General Hospital and Brigham and Women's Hospital were included. Data on demographic, clinical, and laboratory features were collected. Time-to-event survival analysis was performed using a Cox proportional hazards model. Univariate and multivariate regression analyses were performed. RESULTS: We included 124 patients with a diagnosis of MOGAD of which 62.1% (n = 77) were female. The median (IQR) onset age and follow-up time were 31 (16, 45), and 4.08 (2.2, 7.9) years respectively. In total, 40.3% (n = 50) of patients remained monophasic and, 59.7% (n = 74) developed a relapsing course. The median (IQR) time between the index event and the second attack was 3(2, 13.7) months. Starting maintenance therapy following the index event was associated with decreased risk of relapsing disease (HR:0.26; 95%CI: 0.12, 0.54; P < 0.001). Maintenance therapy with intravenous immunoglobulin (HR:0.1; 95% CI:0.01, 0.78, P = 0.02), rituximab (HR: 0.21; 95%CI: 0.08, 0.55; P = 0.001), and mycophenolate mofetil (HR: 0.27; 95%CI: 0.09, 0.77; P = 0.01) was associated with a decreased risk of relapsing disease course. A polyphasic first attack (HR:2.4; 95%CI:1.31, 4.4; P = 0.004) and high CSF protein (HR:2.06; 95%CI: 1.01, 4.16; P = 0.04) were associated with a relapsing course. CONCLUSIONS: In MOGAD patients, starting maintenance therapy following the index event reduces the risk of relapsing disease regardless of age, sex, and onset phenotype, while polyphasic first attack, and elevated CSF protein predict relapsing disease course.

Case report: Transition from anti-CD20 therapy to inebilizumab for 14 cases of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system characterized by recurrent, disabling attacks that affect the optic nerve, spinal cord, and brain/brainstem. While rituximab, targeting CD20-positive B-cells, is used as an off-label therapy for NMOSD, some patients continue to exhibit breakthrough attacks and/or adverse reactions. Inebilizumab, a humanized and glycoengineered monoclonal antibody targeting CD19-positive B-cells, has been FDA approved for the treatment of NMOSD in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Given the limited real-world data on the efficacy and safety of inebilizumab, especially in those transitioning from rituximab, a retrospective chart review was conducted on 14 NMOSD patients from seven centers. Of these, 71.4% (n = 10) experienced a combined 17 attacks during rituximab treatment, attributed to either breakthrough disease (n = 10) or treatment delay (n = 7). The mean duration of rituximab treatment was 38.4 months (3.2 years). Notably, no subsequent attacks were observed during inebilizumab treatment [mean duration of inebilizumab treatment was 19.3 months (1.6 years)], underscoring its potential as an effective treatment for NMOSD. Our data suggest that inebilizumab provides clinical benefit with effective disease control and a favorable safety profile for patients transitioning from rituximab.

Low mortality rate in a large cohort of myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

The mortality rates of individuals with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are currently unknown. This study aimed to assess the mortality rate in a large cohort of patients with MOGAD. Since none of the patients in our cohort died, we estimated the upper limit of a 95% confidence interval of the crude mortality rate in the cohort to be 2.1%. These data suggest that mortality in MOGAD is lower than that reported in other neuroinflammatory diseases and comparable to the age-adjusted mortality rates of the general population in the United States. Additional studies are warranted to confirm this observation.

Is there a link between neuropathic pain and constipation in NMOSD and MOGAD? Results from an online patient survey and possible clinical implications.

BACKGROUND: Neuropathic pain (NP) and constipation are common among people with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and have a negative impact on quality-of-life measures. The possible association between the two symptoms has not been explored. METHODS: Patients with NMOSD and MOGAD, who were members of a closed international Facebook group, were recruited to complete an anonymous survey on REDCap. Participants were queried regarding demographic and disease-related characteristics, the presence and severity of NP and constipation, and whether they believe there is a relationship between the two symptoms. RESULTS: Of the 317 participants who completed the survey, 213 (67.2%) reported a diagnosis of aquaporin-4 (AQP-4) positive NMOSD, 93 (29.4%) - MOGAD, and 11 (3.4%) - double-seronegative NMOSD. The mean age was 43.9 ± 16.4 years; 259 were female (81.7%). 206 participants (65%) reported NP, of whom 133 (64.6%) were being treated for it with one or more medications. 167 participants (52.7%) reported constipation, of whom 67 (40.2%) received one or more medications. 137 of 206 participants with NP (66%) also had constipation. Both symptoms were significantly more common among patients with a history of myelitis. Among patients with NP and constipation, 47 participants (34.3%) thought there was a relationship between the two conditions, with the majority reporting increased severity of NP when constipation severity was increased and, conversely, alleviation of NP when constipation lessened. CONCLUSIONS: NP and constipation were seen in the majority of NMOSD and MOGAD patients with a history of myelitis. Interestingly, one-third of patients with both symptoms reported a link between them, with the majority reporting that NP severity was increased with worse constipation. The possible association opens a possibility of a new approach to managing NP, which tends to be poorly responsive to symptomatic therapies and is associated with worse quality of life in NMOSD and MOGAD. Further studies are warranted to confirm our results.

Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases.

BACKGROUND: The COVID-19 vaccines are currently recommended for people with rare neuroimmunological diseases such as neuromyelitis optica spectrum disorder (NMOSD), MOG-antibody disease (MOGAD), and transverse myelitis. However, the safety profile of the vaccines in this population is uncertain. OBJECTIVE: To report real-world safety data of the COVID-19 vaccines in persons with rare neuroimmunological diseases. METHODS: An anonymous survey was distributed to patients recruited on social media. Participants answered general demographic and disease-related questions, and specific questions about their experiences with the COVID-19 vaccines. RESULTS: 438 participants completed the questionnaire. The median age was 51 (range 18-82 years); 366 were female (83.6%); 102 (23.3%) had associated comorbidities, and 354 (80.1%) were treated with immunotherapies. 242 participants (55.3%) reported a diagnosis of NMOSD; 99 (22.6%) had MOGAD; 79 (18%) had transverse myelitis. 239 participants (66.2%) were younger than 55 years of age. 138 participants (31.5%) reported earlyadverse events. Of these, 93 (67.4%) were < 55 years old, and 45 (32.6%) were > 55 years old (p=0.0086). The most common adverse events were local reactions, including pain, redness, and swelling at the injection site, reported by 155 participants (35.4%). 73 participants (16.7%) reported new or worsening neurological symptoms following the vaccination. Most symptoms occurred within the first week after vaccination and resolved within three days. CONCLUSIONS: This survey indicates an overall favorable safety and tolerability profile of the COVID-19 vaccines among persons with rare neuroimmunological diseases. Longer-term studies are warranted to confirm these data.