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

Indocyanine green angiography findings with Collie eye anomaly in Hokkaido dogs

Collie eye anomaly (CEA) is an inherited, congenital ocular disorder caused by a defective mesodermal differentiation in the posterior segment of the eye. Major ocular finding of CEA is abnormalities of choroidal vessels, that is choroidal hypoplasia. Indocyanine green angiography (IA) is one of the useful ocular examination to observe choroidal vessels in both human and dogs. The purpose of this study was to evaluate IA with CEA in Hokkaido dogs, which is one of the traditional Japanese breed and natural monument in Japan. Ten Hokkaido dogs that had been carried out genetic tests in advance were included in this study. Dogs included in this study had ophthalmic examination, such as menace response, dazzle reflex, direct and indirect pupillary light reflex, slit-lamp biomicroscopy, simple funduscopy, and IA. According to the result of genetic tests, they were classified as 8 affected and 2 carrier dogs. Simple funduscopy revealed choroidal hypoplasia bilaterally and temporal or dorsotemporal area to the optic disc in all affected dogs. With IA, we could observe the abnormalities of choroidal vessels not only at the area coincided with choroidal hypoplasia with simple funduscopy but also at the area detected normal with simple funduscopy in affected dogs. No abnormalities on fundus were observed with both simple funduscopy and IA in all carrier dogs. In conclusion, it was revealed that choroidal hypoplasia in CEA Hokkaido dogs was existed also in the area that could not be observed with simple funduscopy

Aqueous humor SPARC concentration in canine glaucomas

This study was conducted to identify new objective parameters to diagnose and etiologically differentiate canine glaucomas. In the first phase, proteomic analysis was performed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) on the aqueous humor of each single eye of five healthy dogs, three dogs with primary glaucoma, and three dogs with secondary glaucoma. Secreted protein acidic and rich in cysteine (SPARC) was identified as a protein that was expressed in all healthy dogs but not in any of glaucomatous dogs. In the second part of the study, we examined SPARC concentrations in the aqueous humor of each single eye of 13 healthy dogs, 14 dogs with primary glaucoma and 13 dogs with secondary glaucoma by enzyme-linked immunosorbent assay. The SPARC concentration was numerically lower with primary glaucoma (0.486 ± 0.047 ng/ml, mean ± standard error) and numerically higher with secondary glaucoma (0.738 ± 0.089 ng/ml) compared to the control eyes (0.637 ± 0.081 ng/ml). Receiver operating characteristic curve analysis confirmed the ability of the aqueous humor SPARC concentration to differentiate between primary and secondary glaucomas (AUC = 0.72). Thus, 2D-PAGE and MS might be valuable tools for screening of the aqueous humor proteins in canine glaucoma, and the SPARC concentration has a clinical potential in the etiological classification of canine glaucomas

Dark adaptation time in canine electroretinography using a contact lens electrode with a built-in light source

The purpose of this study was to evaluate the dark adaptation time in canine electroretinography (ERG) using a contact lens electrode with a built-in LED. Twelve eyes of six normal laboratory beagle dogs were used and exposed to steady room light at 500 lux for 30 min for light adaption. ERG was recorded at different time points during dark adaptation in sedated and light-adapted beagles. The stimulus intensity was 0.0096 cd/m2/sec. The b-wave amplitude increased significantly until 25 min of dark adaptation, whereas no significant changes in amplitudes were observed after 30 min. Dark adaptation for more than 25 min would be necessary for accurate ERG in canine ERG using a contact lens electrode with a built-in LED