National Hospital Organization Hanamaki Hospital

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1580:"<h3>Background</h3> In MycarinG (NCT03971422; Phase 3), adults with generalised myasthenia gravis (gMG) received one 6-week rozanolixizumab treatment cycle. All patients who enrolled in MG0007 (NCT04650854; open-label extension) received one further treatment cycle with subsequent need-based cycles initiated at the investigator’s discretion. Thus, cycle number and treatment-free intervals varied per patient. <h3>Methods</h3> Clustering analysis was conducted on the number of cycles per year (CPY) in patients with ≥1 cycle from MycarinG and MG0007 (data cut-off: 08 July 2022). Baseline characteristics were assessed for association with CPY using multivariate regression models. Treatment-emergent adverse events were compared among clusters. <h3>Results</h3> Balanced clustering and optimal goodness-of-fit was achieved using three clusters to describe CPY (low: &lt;2.59; medium: 2.59–4.64; high: &gt;4.64). Mean (standard deviation) CPY in each cluster was 1.50 (0.53, n=74), 3.59 (0.60, n=64) and 5.82 (0.72, n=50), respectively. Overall, baseline characteristics were balanced between clusters and were not predictive of CPY for patients. Rozanolixizumab was generally well tolerated across the clusters. <h3>Conclusions</h3> These three treatment clusters demonstrate that rozanolixizumab cycle cadence varies between patients, from 1–7 CPY. This suggests an individualised approach to rozanolixizumab treatment based on each patient’s own gMG experience, as the study included a broad, adult gMG population. rowan.orme{at}ucb.com ";}

Autistic symptoms have been shown to influence functional outcomes and prognosis not only in schizophrenia but also in individuals at clinical high-risk of psychosis (CHR-P) and those experiencing their first-episode psychosis (FEP). However, it remains unclear whether these symptoms reflect enduring traits that persist over time or whether they are states that can improve with treatment in CHR-P and FEP. This study aimed to investigate the one-year trajectory of autistic symptoms in individuals at CHR-P and with FEP. A total of 59 participants who completed a one-year follow-up [CHR-P, n=34; FEP, n=25] were categorized into high and low autistic symptom groups based on baseline symptom severity, as assessed by the Positive and Negative Syndrome Scale Autism Severity Score. We then examined changes in psychiatric symptoms, including autistic symptoms, as well as global and cognitive function, between the two groups over one year. After one year of follow-up, psychiatric symptoms other than autistic symptoms, as well as global and cognitive function, improved in both groups. The significant differences in these symptoms and functions at baseline disappeared after one year. However, while autism symptoms demonstrated some improvement from baseline, the significant differences between the high and low autistic symptom groups persisted. These findings suggest that autistic symptoms may exhibit both transient state and enduring traits in individuals at CHR-P and with FEP. Further studies with larger sample sizes and follow-up periods exceeding one year are needed to validate the long-term stability of these symptoms.

ObjectiveTo evaluate the efficacy and safety of amifampridine (3,4-diaminopyridine) phosphate in Japanese adults with Lambert-Eaton myasthenic syndrome (LEMS).MethodsThe LMS-005 study was an uncontrolled, single-blind (patient blinded), multicenter, one-year phase 3 clinical study. The administration of amifampridine phosphate was started at 15 mg/day, and the dose was increased every 3 to 4 days to determine the optimal dose for each patient. After 7 days of treatment with the optimal dose, efficacy was assessed by evaluating quantitative myasthenia gravis (QMG), subject global impression (SGI), and Clinical Global Impression-Improvement scale (CGI-I) scores.PatientsAdult patients with LEMS were analyzed for safety [n=12, mean age±standard deviation (SD) of 61.1±14.6 years old] and efficacy (n=10, mean age±SD of 60.7±15.9 years old).ResultsIn the efficacy population, the mean±SD [median (interquartile range)] QMG score was 13.2±3.1 [13.5 (11.0, 15.0)] at baseline and 8.0±2.7 [8.0 (6.0, 9.0)] at the end of the treatment period, with a mean±SD [median (interquartile range)] change of -5.2±2.8 [-5.5 (-7.0, -3.0)]. All patients showed a decrease in the QMG score from baseline and experienced improvement in their LEMS symptoms. The SGI/CGI-I scores also improved. Efficacy was maintained until the end of the study. Five patients in the safety population experienced adverse drug reactions, the most common of which was dysesthesia (n=2).ConclusionThis study revealed the long-term efficacy and tolerability of amifampridine phosphate in Japanese adults with LEMS.

Background: In the Phase 3 MycarinG study (MG0003/NCT03971422), one 6-week cycle of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo. After MycarinG, patients could enrol in open-label extension studies (MG0004 then MG0007, or MG0007 directly). Methods: In MG0004 (NCT04124965), patients received once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007 (NCT04650854), after a cycle of rozanolixizumab 7mg/kg or 10mg/kg, subsequent cycles were based on symptom worsening at the investigator’s discretion. Pooled data are reported across MycarinG, MG0004 (first 6 weeks) and MG0007 (final data) for patients receiving ≥2 symptom-driven cycles (efficacy; ≤13 cycles) or ≥1 cycle (safety). Results: 196 patients received ≥1 rozanolixizumab dose of whom 129 received ≥2 symptom-driven cycles (7mg/kg: n=70; 10mg/kg: n=59). Treatment response was maintained from Cycles 1–13: mean change from baseline to Day 43 in MG-Activities of Daily Living score ranged from -3.2 to -4.9 (7mg/kg) and -3.2 to -6.7 (10mg/kg). Quantitative MG and MG Composite scores also improved. Treatment-emergent adverse events (TEAEs) did not increase with repeated cyclic treatment, and most were mild/moderate; the most common event was headache. Conclusions: Rozanolixizumab showed consistent improvements across MG-specific outcomes up to 13 cycles and repeated cyclic treatment was generally well tolerated. Funding: UCB.

Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#

To report the third-year analysis from the postmarketing surveillance (PMS) evaluating real-world effectiveness and safety of eculizumab in adults with anti-acetylcholine receptor antibody-positive (AChR-Ab+) gMG.

Background: Zilucoplan, a macrocyclic peptide complement component 5 inhibitor, sustained efficacy for up to 60 weeks of treatment, with a favourable safety profile in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis in an interim analysis of RAISE-XT (NCT04225871). We evaluate the safety and efficacy of zilucoplan up to 96 weeks. Methods: RAISE-XT, a Phase 3, multicentre, open-label extension study, included patients who participated in the double-blind Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg injections. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: At data cut-off (11 May 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years (N=200). TEAEs occurred in 191 (95.5%) patients; the most common TEAE was COVID-19 (n=64; 32.0%). At Week 96, mean (standard error) change in MG-ADL score from double-blind study baseline was –6.33 (0.49) and –7.83 (0.60) for patients who received zilucoplan 0.3mg/kg and placebo in the double-blind studies, respectively. Conclusions: Zilucoplan demonstrated a favourable long-term safety profile. Efficacy was sustained for 96 weeks in patients who had previously received zilucoplan and who switched from placebo.

To evaluate the long-term safety and efficacy of zilucoplan, a macrocyclic peptide complement component 5 inhibitor, up to 96 weeks in patients with acetylcholine receptor autoantibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) in an interim analysis of RAISE-XT (NCT04225871).