Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

COVID-19 epidemic in Italy and the Pandora's box of inequalities: reopened or never closed?

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Increased burned area in the Pantanal over the past two decades

Wildfires are behaving differently now compared to other time in history in relation to frequency, intensity and affected ecosystems. In Brazil, unprecedented fires are being experienced in the last decade. Thus, to prevent and minimize similar disasters, we must better understand the natural and human drivers of such extreme events. The Brazilian Pantanal is the largest contiguous wetland in the world and a complex environmental system. In 2020, Pantanal experienced catastrophic wildfires due to the synergy between climate, inadequate fire management strategies and weak environmental regulations. In this study, we analyzed recent patterns and changes in fire behavior across the Pantanal based on land use and cover (LULC) classes. The inter-annual variability of the fire and land cover changes between 2000 and 2021 was assessed using BA from MCD64A1 V.6 product and LULC data from Landsat satellite. Our work reveals that fires in the Pantanal over the last two decades tended to occur more frequently in grassland than in others land cover types, but the 2020 fires have preferentially burned forest regions. Large fire patches are more frequent in forest and grasslands; in contrast, croplands exhibit small patches. The results highlight that a broad scale analysis does not reflect distinct localized patterns, thus stratified and refined studies are required. Our work contributes as a first step to disentangling the role of anthropogenic-related drivers, namely LULC changes, in shaping the fire regime in the Pantanal biome. This is crucial not only to predict future fire activity but also to guide appropriated fire management in the region.Ministry of Education (MOE)Nanyang Technological UniversityE.A. acknowledge the Brazilian National Council for Scientific and Technological Development (CNPq) for research grant 303169/2018-4. R.L. was supported by CNPq [grant 311487/2021-1], FAPERJ [grant E26/202.714/2019]; and partially funded by Project Rede Pantanal (FINEP grant 01.20.0201.00). E.P. acknowledge the Nanyang Technological University (#SUG-NAP 3/19EP) and the Ministry of Education of Singapore (#Tier1 RT06/19, #Tier1 2021-T1-001-056)