Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
Neuromyelitis optica spectrum disorder (NMOSD) is a kind of demyelinating disease of central nervous system which mainly affect optic nerve and spinal cord. Because of its serious blindness and disability, how to effectively prevent relapse has become the focus of ophthalmologists. With the deep understanding of the pathogenesis and the progress of scientific and technological means, more and more monoclonal antibodies(mAb) continue to enter clinical trials. B cell surface antigen CD20 blocker, rituximab, has become a first-line drug for the treatment of NMOSD. CD19 blocker, inebilizumab, can reduce the recurrence and disability of NMOSD patients. The addition of interleukin 6 receptor blocker, satralizumab, and complement C5 inhibitor, eculizumab, reduce the recurrence. Some mAbs such as natalizumab and alemtuzumab may not be effective for the treatment of NMOSD. The expansion of mAb treatment indications and the launch of new drugs still require more clinical trials which are large-scale and international cooperation. At the same time, its potential adverse events and cost issues cannot be ignored.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (eculizumab, inebilizumab, and satralizumab). Neurol Neuroimmunol Neuroinflamm published international Delphi consensus on the management of AQP4-IgG+ NMOSD in May 31, 2023. Twenty-five statements reached consensus after two voting rounds by 24 Delphi panel experts. Inebilizumab and satralizumab have been listed in China, and off-label immunosuppressants and biologics are also used in clinical practice. However, there are no standard treatment recommendations in use of these biologics and maintenance therapy of NMOSD. Therefore, the interpretation of this consensus, focusing on the initial use of monoclonal drugs, the conversion between monoclonal drugs and immunosuppressants, as well as the application and safety of special populations, is conducive to improving the normative and effective use of of monoclonal drugs in NMOSD y ophthalmologists and neurologists
Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder (NMOSD). Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was (26.2±12.0) years. Duration of disease was 2.3 - 25.8 years, the mean duration was (9.2±5.9) years. Best corrected vision activity (BCVA), expanded disability status scale (EDSS), annualized relapsing rate (ARR) were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was (28.4±4.9) months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye (t=4.256), ARR (t=2.900), EDSS (t=4.620) with the significant differences (P＜0.05).Thirteen relapses in 9 patients were observed. B lymph cells were more than 0.01% in all relapses. There was no significant difference on the BCVA in better eye (t=1.840, P＞0.05). There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age (t=0.67, P=0.51), whether underwent plasma exchange treatment (χ2=1.61, P＞0.05), with/without auto-immune antibody ratio (χ2=1.61, P＞0.05). Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated.
ObjectiveTo preliminary investigate the impact of the diagnosis-related groups (DRG) payment method reform on the diagnosis and treatment of inpatient medical insurance patients with neuromyelitis optica spectrum disorders (NMOSD), and to propose potential improvement strategies. MethodsA single-center, retrospective study. From October 1, 2020, to September 30, 2022, 44 hospitalized medical insurance patients with acute-phase NMOSD diagnosed and treated at the First Affiliated Hospital of Northwest University (Xi'an First Hospital) were included in the study. Among them, there were 11 males and 33 females, with an average age of (40.8±20.2) years. According to the implementation time of DRG payment, patients were divided into two groups: group A, which consists of cases one year before the implementation of DRG payment from October 1, 2020 to September 30, 2021, and group B, which consists of cases one year after the implementation of DRG payment from October 1, 2021 to September 30, 2022, with 20 and 24 cases, respectively. Detailed information such as hospitalization duration, treatment methods, and hospitalization costs of the two groups of patients was collected. Comparative analysis was conducted on hospitalization costs and treatment methods between the two groups. For intergroup comparison, t-test was used for normally distributed data, and Mann-Whitney U test was used for skewed distributed data. ResultsAmong the 44 patients, 5 cases (5/24, 20.8%) received plasma exchange (PE) treatment, all of whom were in group B. The numbers of patients who received and did not receive intravenous immunoglobulin (IVIG) treatment were 9 and 11 in group A, respectively, and 7 and 12 in group B (except for 5 cases who received PE treatment), respectively. Compared with group A, there was no significant decrease in hospitalization duration (t=0.004) and total hospitalization costs (Z=0.036), as well as costs for western medicine (Z=0.036), examinations (Z=0.011), laboratory tests (Z=0.040), treatments (Z=0.017), and nursing (Z=3.131) in group B, and the differences were not statistically significant (P＞0.05). For patients receiving PE treatment, except for the cost of western medicine (Z=0.062, P=0.804), the other costs (Z=8.288, 5.013, 11.400, 10.925, 9.126) were significantly higher than those of patients not receiving PE treatment, and the hospitalization duration (t=20.474) was significantly prolonged, with statistically significant differences (P＜0.05). The total hospitalization costs of patients receiving IVIG treatment were significantly higher than those not receiving IVIG treatment in both group A and group B, with statistically significant differences (Z=7.690, 10.314; P＜0.05). There was no statistically significant difference in the comparison of total hospitalization costs between patients receiving IVIG treatment in group A and group B (Z=0.137, P＞0.05). ConclusionsThere is no significant decrease in various hospitalization costs of NMOSD medical insurance patients in Xi'an after the implementation of DRG payment, especially for patients receiving PE treatment. It is suggested to optimize the rate stratification of NMOSD patients when implementing DRG payment methods.
The first edition of “The Chinese expert consensus on the diagnosis and treatment of optic neuritis” have been published in Chinese Journal of Ophthalmology in 2014. Seven years later, more evidence-based medicine has been accumulated in the treatment of optic neuritis. It is necessary to update or formulate guidelines to guide clinical practice. Based on the methods and procedures for developing evidence -based guidelines, Neuro-Ophthalmology Group of Ophthalmology Branch of Chinese Medical Association and Evidence-based Medicine Centre of Lanzhou University/World Health Organization Collaborating Centre for Guideline Implementation and Knowledge Translation created the first “An evidence-based guideline for the diagnosis and treatment of demyelinating optic neuritis in China (2021)”, which aimed to improve the level of clinical diagnosis and treatments of demyelinating optic neuritis. This guideline proposes a new subtype classification of demyelinating optic neuritis to guide precision treatment. It also gives new suggestions about clinical treatment hotspots in the acute and chronic phases, including the application of immunosuppressants and rituximab and other biological agents.
Neuromyelitis optica (NMO) is an autoimmune inflammatory diseases of the central nervous systems (CNS) mainly affecting the optic nerves and spinal cord. It has the characteristics of high recurrence rate and poor prognosis. NMO related optic neuritis is a common neuro-ophthalmic disease which often results in permanent visual loss or even blindness. Aquaporin 4 (AQP4) antibody is a specific and pathogenic autoantibody in NMO patients. Although AQP4 is expressed in multiple tissues, NMO pathology is remarkably limited to the CNS. Corticosteroids and other immunosuppressive drugs are the standard managements for NMO patients, in order to reduce the relapses and the severity of the acute attack. Multiple avenues of investigation in the laboratory have significantly advanced our understanding of NMO pathophysiology, which is helpful for our understanding of immunologic and nonimmunologic mechanisms. Many offer significant means for NMO therapy by selectively targeting pathways. In the future, moving these agents from the bench to the bedside offers the opportunity to identify safe and effective therapies that limit CNS injury and preserve visual function.
ObjectiveTo observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients, and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.MethodsA retrospective case study. From September 2009 to March 2014, 132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study. Among the patients, 74 patients (56.06%) were involved in optic nerve for the first time, among which 63 patients (47.72%) were involved in optic nerve alone, and 11 patients (8.33%) were involved in optic nerve and spinal cord at the same time. The recurrence rate was 62.88% (twice or more). All patients underwent BCVA, slit lamp microscope, fundus examination, thyroid function, sex hormones, and serum AQP-4Ab detection. BCVA was recorded at admission and before discharge from hospital, and worse BCVA was recorded in binocular patients. The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.ResultsAmong the 74 patients with optic nerve involved in the first onset, 50 patients with BCVA＜0.1 at the initial diagnosis (67.57%); AQP-4Ab positive was found in 56 patients, which including 13, 9 and 34 patients of AQP-4Ab titer 5 - 60, 61 - 100 and ＞100 RSRU/ml. After 2 weeks of treatment, BCVA improved in 40 patients (71.42%), including 11 (84.62%), 6 (66.67%) and 23 (67.64%) of AQP-4Ab titer 5 - 60, 61 - 100 and ＞ 100 RSRU/ml. Among 132 patients, 98 patients (74.24%) were AQP-4Ab positive. There were 73 patients (55.30%) with abnormal immune rheumatoid index.ConclusionsThe optic nerve is involved in 56.06% patients with NMO for the first time, and 67.57% of the patients had poor vision with BCVA＜0.1. BCVA prognosis is better in patients with serum AQP-4Ab titer of 5 - 60 RSRU/ml.