Dataset Information

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study.

ABSTRACT: Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a devastating autoimmune inflammatory disorder of the central nervous system, which can result in blindness or paralysis. Currently, there is a dire need for new treatment options in the clinic. Several case series have shown that mycophenolate mofetil (MMF) may be an effective treatment for NMOSD patients. The dosing of MMF in the treatment of NMOSD has been poorly studied. Therefore, we evaluated the efficacy, tolerability, influential factors and optimal dosage of MMF in Chinese patients with NMOSD.A case series of 109 NMO or NMOSD (limited forms of NMO with seropositive AQP4-IgG) patients were retrospectively analyzed and followed up. Out of the 109 patients, 86 patients had received MMF for 6 months or longer and were included for efficacy assessment.When comparing the annualized relapse rate (ARR) of MMF treatment with that of pre-MMF treatment period, MMF was found to significantly reduce ARR in 75 (87%) patients (p < 0.0001). The median pre-treatment Expanded Disability Status Scale (EDSS) score in remission decreased from 3 (range, 0-8.5) to 2.5 (range, 0-8) at the last follow-up (p = 0.006), yet no significant difference was found in the visual score. The higher doses of MMF (1750 mg/d to 2000 mg/d) significantly lowered the relapse risks compared with lower doses (1000 mg/d or less, p < 0.0001) or moderate doses (1250 to 1500 mg/d, p = 0.031). Coexisting with systemic autoimmune diseases (HR, 2.418; p = 0.0345) and attack number before MMF initiation (HR, 1.117; p = 0.02) were important risk factors for relapses. MMF was generally well tolerated with adverse effects occurring in 21 patients (19%). While four patients decreased their daily doses because of the adverse effects, only one patient stopped MMF treatment.MMF is generally effective and well tolerated in Chinese NMOSD patients. High-dose MMF was more potent than the lower dose for NMOSD patients, with 1750 mg of daily MMF being the recommended dosage for Chinese patients with NMOSD. MMF treatment reduces the frequency of relapses and improves the quality of life for patients with this debilitating disease.

SUBMITTER: Jiao Y

PROVIDER: S-EPMC5911949 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionNeuromyelitis optica spectrum disorders (NMOSD) is an inflammatory and heterogeneous astrocyte disorder of the central nervous system with the characteristic of higher incidence in women and Asian people. Most patients with NMOSD have a course of recurrence and remission that is prone to cause paralysis and blindness. Several studies have confirmed the efficacy and promising prospect of mycophenolate mofetil (MMF) in the treatment of NMOSD. Yet its therapeutic effect and safety are controversial. Although there has been two published literature that is relevant to the topic of this study, both of them have certain defects, and they can only provide answers about the efficacy or safety of MMF in the treatment of NMOSD from partial perspectives or conclusions. This research aims to perform a direct and comprehensive systematic review and meta-analysis to evaluate MMF's effectiveness and safety in treating NMOSD.Methods and analysisThis systematic review will cover all comparative researches, from randomised controlled trials to cohort studies, and case-control study. A relevant literature search will be conducted in PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and Chinese Biomedical Literature Database from their inception to 31 June 2020. We will also search registers of clinical trials, potential grey literature and abstracts from conferences. There are no limits on language and publication status. The reporting quality and risk of bias will be assessed by two researchers independently. Expanded Disability Status Scales and annualised relapse rate will be evaluated as the primary outcome. The secondary outcomes will consist of the frequency and severity of adverse events, best-corrected visual acuity, relapse-free rate and time to the next attack. A meta-analysis will be performed using RevMan V.5.3 software provided by the Cochrane Collaboration and Stata V.12.0.Ethics and disseminationBecause the data used for this systematic review will be exclusively extracted from published studies, ethical approval and informed consent of patients will not be required. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms.Prospero registration numberCRD42020164179.

Project description:IntroductionAs an autoimmune central nervous system disease characterized by inflammation and demyelination, neuromyelitis optica (NMO) has been extensively investigated. A specific antigenic target, astrocytic water channel aquaporin-4 (AQP4) has already been identified, and it can be recognized explicitly by the autoantibody marker NMO-IgG. Along with the immune attacks, clinical disabilities would gradually accumulate. As there has been no validated and well-recognized therapy for NMO till now, preventing and postponing attack using immunosuppressive therapies is the primary treatment option.MethodsIn the current retrospective study, the effect of immunosuppressive agents was investigated through a long-term follow-up. To assess the long-term effectiveness and safety of rituximab (RTX), azathioprine (AZA), and mycophenolate mofetil (MMF) therapies, all 129 patients with NMO spectrum disorders (NMOSD) who received at least one of these treatments were studied, including 55 seropositive for AQP4-Ab and 74 seronegative for AQP4-Ab.ResultsThe median post-treatment annualized relapse rate (ARR) was lower than the pre-treatment rates in all AQP4+Ab groups (from 1.0 to 0.7 in RTX, from 0.8 to 0.3 in AZA, and from 0.85 to 0.35 in MMF). Meanwhile, the ARR also decreased in all AQP4-Ab groups (from 0.3 to 0.2 in RTX, from 0.9 to 0.5 in AZA, and from 0.9 to 0.4 in MMF). Disability condition improved in the Expanded Disability Status Scale (EDSS) in all AQP4+Ab groups (from 4.0 to 2.75 in RTX, from 3.5 to 2.5 in AZA, and from 3.0 to 2.0 in MMF) and in all AQP4-Ab groups (from 3.0 to 2.5 in RTX, from 3.0 to 2.5 in AZA, and from 3.5 to 2.0 in MMF). There was no statistically significant difference between the post-treatment and pre-treatment changes of EDSS and ARR in the RTX, AZA, and MMF groups (P > 0.05). However, according to Kaplan-Meier survival analysis, RTX-treated patients were more likely to be relapse-free after long-term follow-up than those who received AZA or MMF therapy. Meanwhile, adverse effects were noted in three out of 23 patients with RTX treatment, five of 32 with AZA treatment, and three of 21 with MMF treatment. No serious adverse events were observed in all treatment groups during the study.ConclusionsRTX, AZA, and MMF therapies efficiently lowered the relapse frequency and disability in both of the AQP4-Ab seropositive or seronegative patients with NMO. Furthermore, low dosage of RTX is recommended for the patients with NMO owing to its long-term effectiveness and safety.

Project description:Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory condition of the central nervous system. The extent of disability depends on the severity of the disease and the number of relapses. Although azathioprine is currently the main treatment for patients with NMOSD in Thailand, patients often relapse during its use. Hence, it is argued that there are other drugs that would be more effective. The purpose of this study is to evaluate, from a societal perspective and from the economic impact on Thailand's healthcare system, the cost utility of treatment with mycophenolate mofetil (MMF) and rituximab in patients resistant to azathioprine. The Markov model with a one-year cycle length was applied to predict the health and cost outcomes in patients with NMOSD over a lifetime. The results showed that rituximab exhibited the highest quality-adjusted life year (QALY) gains among all the options. Among the rituximab-based treatments, the administration of a rituximab biosimilar with CD27+ memory B cell monitoring proved to be the most cost-effective option. At the willingness-to-pay threshold of 160,000 Thai baht (THB), or 5,289 US dollar (USD), per QALY gained, the treatment exhibited the highest probability of being cost effective (48%). A sensitivity analysis based on the adjusted price of a generic MMF determined that the treatment was cost effective, exhibiting an incremental cost-effectiveness ratio of -164,653 THB (-5,443 USD) and a 32% probability of being cost effective. The calculated budget impact of treating patients resistant to conventional therapy was 1-6 million THB (33,000-198,000 USD) for the first three years, while after the third year, the budget impact stabilized at 3-4 million THB (99,000-132,000 USD). These data indicate that, in Thailand, treatment of drug resistant NMOSD with a rituximab biosimilar with CD27+ memory B cell monitoring or treatment with a generic MMF would be cost effective and would result in a low budget impact. Therefore, the inclusion of both the rituximab biosimilar and a generic MMF in the National Drug List of Essential Medicine for the treatment of NMOSD may be appropriate.

Project description:Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF.ImportanceNeuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Dataset Information

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets