Neurology and Therapy最新文献

Myasthenic crisis (MC) is a potentially fatal complication of myasthenia gravis (MG), often requiring intensive care and rescue therapies such as intravenous immunoglobulin (IVIG) and corticosteroids. Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, offers a novel approach by selectively reducing circulating pathogenic IgG. We describe a 77-year-old man with anti-AChR-positive generalized MG who developed a severe MC, with little response to IVIG and high-dose corticosteroids. Intravenous efgartigimod was administered as rescue therapy with rapid and sustained clinical improvement. This case supports the utility of efgartigimod in MC unresponsive to conventional therapies, including in older patients with significant comorbidities.

Introduction: Evidence directly comparing newer antiseizure medications (ASMs) is limited but crucial for guiding treatment decisions. This study compared the real-world effectiveness and tolerability of brivaracetam (BRV), lacosamide (LCM) and perampanel (PER) as add-on therapy in adults with epilepsy, applying a causal-inference extension of the COMPARE study. The aim of this approach was to overcome the limitations of standard multivariable analyses, better approximate causal effects, and reinforce the credibility of the results.

Methods: Data were retrospectively collected in the Italian multicentre COMPARE study. To emulate a randomized setting, we estimated multinomial propensity scores and applied stabilized inverse probability weights. The primary analysis used a log-logistic accelerated failure time model to estimate time-to-treatment discontinuation, adjusting for adverse events (AEs), clinical response and follow-up duration. Secondary analyses evaluated changes in total and concomitant drug load and tolerability over time.

Results: Among the 850 subjects included in this analysis (259, 240 and 351 receiving LCM, BRV and PER, respectively; 53.4% female; median age 43 years), the estimated probability of 12-month retention was highest for LCM (86.1%), followed by BRV (79.1%) and PER (75.4%). Long-term trends suggested convergence of PER and LCM retention, whereas BRV discontinuation remained higher. In the adjusted analyses, BRV and PER were associated with shorter time-to-treatment discontinuation than LCM, but this negative effect decreased over time, while the beneficial effect of clinical response strengthened. Total drug load increased across all groups but remained lowest for LCM; concomitant ASM load decreased, particularly among responders. AEs were mostly mild, with dizziness, irritability and somnolence the most common AEs. AE rates were initially higher for PER and BRV, but differences diminished over time.

Conclusion: Treatment discontinuation in epilepsy emerges as a dynamic process shaped by both tolerability and clinical response. Early persistence was higher for LCM, whereas long-term retention was improved for BRV and PER. These results support a personalized approach to ASM selection that integrates early tolerability with sustained effectiveness.

Introduction: Oral corticosteroids (OCSs) and nonsteroidal immunosuppressant therapies (NSISTs) remain widely used for the clinical management of patients with generalized myasthenia gravis (gMG), despite well-documented risks. Newer targeted biologic therapies have demonstrated concomitant immunosuppressant therapy reduction; however, long-term comparative real-world evidence remains limited. This retrospective, observational study compared OCS and NSIST use in patients in the USA receiving one of the following US Food and Drug Administration-approved therapies for gMG treatment: ravulizumab or eculizumab (complement protein C5 inhibitor therapies [C5ITs]) or efgartigimod (neonatal Fc receptor antagonist).

Methods: Patients were identified using the IQVIA PharMetrics^® Plus claims database from January 1, 2015 to March 31, 2024. Eligible patients had ≥ 2 MG claims filed ≥ 30 days apart by a nonophthalmologic specialist. Treatment index date was the date of first ravulizumab, eculizumab, or efgartigimod claim. All patients assessed were continuously treated with ravulizumab, eculizumab, or efgartigimod during the 12-month follow-up period. Baseline OCS dose was estimated using claims data 3 months before the index date. Change from baseline in OCS average daily dose (ADD), OCS tapering, and NSIST use were assessed over 3-month intervals during the 12-month post-index follow-up period.

Results: After 12 months of continuous treatment, the C5IT cohort experienced a significantly greater mean reduction from baseline in OCS ADD compared to the efgartigimod cohort (C5IT, - 11.2 mg/day; efgartigimod, - 3.6 mg/day; P = 0.034), and fewer patients were taking OCS ADD > 30 mg/day (C5IT, 7.5%; efgartigimod, 22.2%). The percentage of patients with NSIST claims decreased by 28.3% within the first 12 months in the C5IT cohort (baseline, 55.2%; month 12, 39.6%) and remained stable in the efgartigimod cohort (baseline, 48.9%; month 12, 48.9%).

Conclusion: These results from US clinical practice suggest greater reductions in OCS and NSIST concomitant therapy for patients treated with ravulizumab or eculizumab compared with efgartigimod.

Alzheimer's disease (AD) remains the most common form of dementia in elderly populations. Accurately diagnosing early forms of dementia and AD remains a significant clinical challenge, especially in fast-paced primary care settings. Informant-based questionnaires that rely on close caregivers of the patients, such as the Informant Questionnaire on Cognitive Decline in the Elderly, the Ascertain Dementia 8-Item, the Quick Dementia Rating System, and the Alzheimer's Questionnaire, have recently been shown to be a valuable supplement to current standards of diagnosis, such as performance-based tests. This review aimed to explore the key characteristics of various informant-based questionnaires and evaluate their efficacy in the medical setting. Analysis of each test demonstrated that informant-based assessments show a strong ability to detect cognitive impairment early on in its pathology and can highlight gradual decline over time, compared with the single-timeframe evaluations that performance-based tests provide. Informant-based questionnaires are also able to circumvent challenges associated with the patient's education level, language, and other cultural biases, thus making them useful in diverse populations. When used in conjunction with performance tests, informant-based tests can significantly streamline the diagnostic process for dementia and enhance management and treatment strategies. Further research is advised to effectively integrate these tests into routine clinical practice and establish a new standard of care.

Introduction: While clinical trials have established the efficacy of immunoglobulin (Ig) to treat chronic inflammatory demyelinating polyneuropathy (CIDP), real-world data are limited. This study evaluated real-world effectiveness of Ig among patients with CIDP in terms of progressive use of assistive devices as a proxy for deteriorating clinical disability.

Methods: Adults diagnosed with CIDP by a neurologist from 1/2015 to 11/2021 and with a documented nerve conduction study were identified using linked medical and pharmacy claims and electronic medical record (EMR) data in the United States (US). Patients receiving Ig were propensity score matched to patients without Ig. Claims for assistive devices were used as a proxy for disability and assessed over 6-month baseline and follow-up periods. Deterioration was defined as ≥ 1 post-index claim for an assistive device indicating a higher level of disability than observed at baseline. Changes in anticonvulsant, antidepressant, and opioid use were assessed as secondary outcomes.

Results: The study sample comprised 1302 Ig-treated and non-Ig-treated matched pairs (mean age 61 years and ~ 40% female). Approximately 40% fewer Ig-treated patients had ≥ 1 level of deterioration (3.3% vs. 5.4%, p = 0.0104) and ≥ 2 levels of deterioration (3.1% vs. 5.1%, p = 0.0079) in assistive device use. Anticonvulsant (48.0-44.8%) and opioid use (39.2-33.3%; both p < 0.0001) decreased from baseline to follow-up in Ig-treated patients but remained unchanged for non-Ig-treated patients. Among patients with baseline opioid use, a higher proportion of Ig-treated patients had opioid improvement over the post-index period (41.5% vs. 32.1%, p = 0.0021).

Conclusion: Our findings support the effectiveness of Ig therapy in CIDP. The benefits of Ig seen in clinical trials of maintained or improved disability scores appear to be reflected in the real world by less deterioration in assistive device use and lesser use of anticonvulsants, antidepressants, and opioids.

Introduction: Donanemab has been developed as an amyloid-targeting therapy (ATT) for mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD). In registration trials involving donanemab, a treat‑to‑clearance approach was used, in which patients discontinued ATT when amyloid plaque levels decreased below a predefined threshold, which differs from previously available symptomatic treatments for AD. Our study explored care partners' perceptions regarding ATT and treat‑to‑clearance.

Methods: This was a cross-sectional, qualitative interview study. Care partners of individuals with MCI or mild dementia due to AD participated in online semi-structured interviews about their perceptions regarding the impact of MCI or mild dementia diagnoses due to AD, the burden of supporting, and use/cessation of ATT. The qualitative data from the interviews were analyzed using a thematic approach.

Results: The participants were 22 care partners (5 male/17 female), and their median age was 59 (range 35-81) years. The most common relationships between care partners and the individuals with AD were child (50.0%) and spouse/partner (45.5%); 68.2% of the care partners lived with the individuals with AD. Thematic analysis identified three major classifications (Thoughts regarding therapy; Treat‑to‑clearance; and Burdens of support), along with 15 themes and five sub-themes. Care partners expressed experiencing mental burden and time constraints, while treat‑to‑clearance could save care partners' time by reducing hospital waiting time and alleviating financial burden. Confirming the clearance of amyloid β plaques provided care partners with a sense of relief, while they remained concerned about the potential progression of AD symptoms and sought follow-up care after stopping treatment.

Conclusions: These results suggest that providing clear explanations and facilitating shared decision-making when introducing ATT, as well as introducing follow-up care and long-term evidence after stopping treatment, are needed.

Introduction: Oral corticosteroids (OCS) are commonly used to control symptoms in patients with myasthenia gravis (MG). Long-term high-dose OCS use is associated with serious side effects, but the real-world clinical impact of high-dose OCS in patients with MG is not well understood. The main objectives of this study were to evaluate healthcare resource utilization and clinical complications associated with high-dose versus low-dose OCS use in Japanese patients with MG.

Methods: A retrospective cohort study was performed using JMDC, a Japanese claims database. Patients with newly diagnosed MG (incident cases) were identified, and the date of the first diagnosis of MG was defined as the index date. Patients were stratified into two groups by OCS dose level (high-dose OCS ≥ 7.5 mg/day; low-dose OCS < 7.5 mg/day; based on the average dose in the population during the follow-up). Patient characteristics, treatments, long-term hospitalization (≥ 10 days cumulative per year), and corticosteroid-related complications were assessed.

Results: Of 2107 patients with an incident MG diagnosis, 576 were on OCS (high-dose OCS, 210; low-dose OCS, 366) during the follow-up period. There were no obvious differences in baseline comorbidities between the high- and low-dose OCS groups. A significant increase in long-term hospitalization was observed in the high-dose OCS versus the low-dose OCS group (adjusted odds ratio [95% CI], 1.832 [1.180, 2.845], P = 0.007). A greater proportion of patients in the high-dose OCS group versus the low-dose OCS group received ≥ 1 course per year of in-hospital intravenous immunoglobulin (34.8% vs. 15.3%), plasma exchange therapy (16.2% vs. 8.2%), and intravenous methylprednisolone pulse therapy (33.3% vs. 24.0%). The incidence of new complications such as diabetes, osteoporosis, osteoporotic fractures, neuropsychiatric disease, and sepsis was significantly (P < 0.05) higher with high- versus low-dose OCS.

Conclusion: Use of high-dose OCS in patients with MG was associated with adverse outcomes, including increased rates of long-term hospitalizations and clinical complications.

Introduction: High-dose intravenous methylprednisolone (IVMP) is effective in treating generalized myasthenia gravis (gMG), but early-stage transient aggravation and MG crisis can occur. This study evaluated the safety and efficacy of efgaitigimod in combination with different doses of IVMPs in patients with severe gMG.

Methods: This was a single-center, retrospective cohort study that retrospectively collected patients with myasthenia gravis who presented to Hebei Myasthenia Gravis Diagnosis and Treatment Center from December 2023 to May 2024, divided into IVMP monotherapy (1000 mg, Group A, n = 20) or efgartigimod combined with IVMP: 1000 mg (Group B, n = 7), 500 mg (Group C, n = 10), or 250 mg (Group D, n = 20). Patients received efgartigimod (10 mg/kg) intravenously on days 1 and 8 while receiving IVMP. Efficacy was assessed via quantitative myasthenia gravis (QMG) scores at baseline, week 2, and week 12.

Results: Groups A, C, and D demonstrated progressive QMG reductions over 12 weeks. Group B showed a week 12 QMG rebound (vs. week 2) but remained below baseline. At week 2, Group A had significantly less QMG improvement than Group B (p = 0.004), which was not different from group C/D. After 12 weeks, no significant difference was found among the groups (p = 0.639). Transient exacerbations and adverse events were significantly higher in Group A versus C/D.

Conclusion: Efgartigimod combined with 250 mg IVMP is associated with improvement of symptoms, reduction of transient exacerbations, and adverse event rates compared with higher IVMP doses or IVMP monotherapy, offering a promising regimen for severe gMG.

Trial registration: Chinese Clinical Trial Registry (Chictr2400080921).