Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. METHODS: RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). FINDINGS: Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. INTERPRETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. FUNDING: UCB Pharma.

Immunological, Clinical, and Epidemiological Features of Guillain-Barré Syndrome Associated with SARS-CoV-2 Infection

Objectives. There is a growing interest in understanding the association between Guillain-Barré syndrome (GBS) and SARS-CoV-2 infection. The aim of this study was to analyse various characteristics of GBS before and after the pandemic outbreak and thus identify possible distinctive features of GBS associated with SARS-CoV-2 (GBS-S). Material and Methods. In our centre, we retrospectively reviewed the records of patients diagnosed with GBS between January 2018 and March 2022. Epidemiological, clinical, and immunological data were analysed and compared between patients with GBS according to the time of diagnosis and antecedent events. Results. Thirty-nine patients with GBS were included: nine (23.1%) were diagnosed with GBS-S. GBS-S was most frequent in 2020 (6/13, 46.1%). Most of these patients developed a postinfectious classic demyelinating variant (4/9, 44.4%) with frequent bilateral facial paralysis (4/9, 44.4%). Serum antiganglioside antibodies (AGAs) were found in 1/9 patients with GBS-S. Serum anti-SSA/Ro60 antibodies were highly prevalent in GBS-S (7/9 (77.8%) vs. 3/11 (27.3%), p = 0.019). Three cases associated with SARS-CoV-2 vaccination (GBS-V) were detected. Of note, two had bilateral facial paralysis and anti-SSA/Ro60 antibodies. Conclusion. Our findings suggest that SARS-CoV-2 has become an important antecedent event associated with GBS in our setting. GBS-S shows a postinfectious demyelinating immune-mediated profile with negative serological testing for AGAs. Serum anti-SSA/Ro60 antibodies were found frequently in these patients. Bilateral facial paralysis stands out as a possible characteristic clinical feature both in GBS-S and GBS-V. Larger, prospective studies are needed for a better understanding of its immunopathogenesis. [ FROM AUTHOR]

Increased worsening of amyotrophic lateral sclerosis patients during Covid-19-related lockdown in France.

Covid-19-related lockdown (LD) in France precluded in-person follow-up in referral ALS centers. ALS patients' evolution and worsening before and during LD were studied to analyze its impact. A total of 84 patients were identified. The monthly rate of ALSFRS-R decline during LD was 1.06 ± 1.42 and was significantly increased compared to the pre-LD period, 0.58 ± 0.73, corresponding to an 83% increase (p = 0.007). Weight loss was unchanged between pre-LD and LD, gender and site of onset did not influence the rates of change of ALSFRS-R score. Several factors may be implicated in this increased severity of ALS during LD, such as psychological consequences of LD, interruptions of physiotherapy and speech therapy, or in-patient visits both to the tertiary center and the GP. Physicians and health authorities should be aware of that, in order to prevent the consequences of future sanitary restrictions.