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Objectives: This post-hoc analysis evaluates the long-term efficacy of efgartigimod versus placebo in adult patients with generalized myasthenia gravis (gMG) with acetylcholine-receptor autoantibodies (AChR-Ab+), based on data from the ADAPT RCT and its open-label extension ADAPT+., Methods: Changes from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores were assessed by treatment group over the ADAPT (up to 20 weeks) and ADAPT+ time horizon (extended to 64 weeks for efgartigimod group patients). Response to treatment was defined as (Meriggioli, 2009 [3] ) 5-point reduction in QMG or (Meriggioli, 2009 [3] ) 3-point reduction in MG-ADL vs. baseline values., Results: AChR-Ab+ patients treated with efgartigimod spent a substantially greater percentage of time in response in ADAPT based on at least a 5-point change in QMG compared to the placebo group (44 % versus 13 % respectively, p = 0.0034). Analyses based on a 3-point change in MG-ADL in ADAPT showed the percentage of time in response was nearly double for efgartigimod versus placebo (59 % versus 30 % respectively, p = 0.010). These trends were also maintained using different response definitions, as well as in patients with and without prior immune therapy exposure and by time from diagnosis (<7 years versus ≥7 years)., Conclusions: The clinical benefit of efgartigimod was sustained over repeat treatment cycles and maintained over the long term. Response to treatment was consistent regardless of response definition and was repeated in different patient subgroups. Overall, the results of this analysis indicate that efgartigimod is an effective therapeutic option, demonstrating a robust benefit among AChR-Ab+ patients with gMG., Competing Interests: Declaration of competing interest CQ, GP, EB and DG are employees of argenx. SD and AG are employed by Services in Health Economics (SHE). SHE received fees from argenx in relation to this study. James F Howard Jr.: Research funding (paid to his institution) from Ad Scientiam, Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, MGFA, Muscular Dystrophy Association, NIH, PCORI, and UCB Pharma; honoraria/consulting fees from AcademicCME, Alexion, AstraZeneca Rare Disease, argenx, Biologix Pharma, CheckRare CME, F. Hoffmann-LaRoche Ltd., Horizon Therapeutics plc (now Amgen), Medscape CME, Merck EMB Serono, NMD Pharma, Novartis Pharma, PeerView CME, Physicians' Education Resource (PER) CME, PlatformQ CME, Regeneron Pharmaceuticals, Sanofi US, UCB Pharma, and Zai Labs; non-financial support from Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Toleranzia AB, UCB Pharma and Zai Labs.RM received funding for Travel, Meeting attendance or Advisory Board participation from Alexion, argenx, Biomarin, Catalyst, SANOFI, Regeneron and UCB., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition F g = 4 ↔ F e = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.

Smart electromagnetic interference (EMI) shielding materials are of great significance in coping with the dynamic performance demands of cutting-edge electronic devices. However, smart EMI shielding materials are still in their infancy and face a variety of challenges (e.g., large thickness, limited tunable range, poor reversibility, and unclear mechanisms). Here, we report a method for controllable shielding electromagnetic (EM) waves through subwavelength structure changes regulated by the customized structure via a direct printing route. The highly conductive MXene ink is regulated with metal ions (Al 3+ ions), giving superb metallic conductivity (∼5000 S cm -1 ) for the printed lines without an annealing treatment. The reversible tunability of EMI shielding effectiveness (SE) ranging from 8.2 dB ("off" state) to 34 dB ("on" state) is realized through the controllable modulation of subwavelength structure driven by stress. This work provides a feasible strategy to develop intelligent shielding materials and EM devices.

There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG., (© 2023. The Author(s).)

Introduction: For patients with generalized myasthenia gravis (gMG), the association between symptom severity, often measured with the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument, and utility values is unknown., Methods: Data was analyzed from the phase 3 ADAPT trial, which included adult patients with gMG randomly assigned to treatment with efgartigimod + conventional therapy (EFG + CT) or placebo + CT (PBO + CT). MG-ADL total symptom scores and the EQ-5D-5L, a measure of health-related quality of life (HRQoL), were collected biweekly up to 26 weeks. Utility values were derived from the EQ-5D-5L data with the United Kingdom value set. Descriptive statistics were reported for MG-ADL and EQ-5D-5L at baseline and follow-up. A normal identity-link regression model estimated the association between utility and the eight MG-ADL items. A generalized estimating equations (GEE) model was estimated to predict utility based on the patient's MG-ADL score and treatment received., Results: A total of 167 patients (84 EFG + CT, 83 PBO + CT) contributed 167 baseline and 2867 follow-up measurements of MG-ADL and EQ-5D-5L. EFG + CT-treated patients experienced more improvements than PBO + CT-treated patients in most MG-ADL items and EQ-5D-5L dimensions, with the largest improvements observed in chewing, brushing teeth/combing hair, eyelid droop (MG-ADL); self-care, usual activities, mobility (EQ-5D-5L). The regression model indicated that individual MG-ADL items contributed differently to utility values, with the largest impact from brushing teeth/combing hair, rising from a chair, chewing, and breathing. The GEE model showed that each unit improvement in MG-ADL led to a statistically significant utility increase of 0.0233 (p < 0.001). In addition, a statistically significant improvement of 0.0598 (p = 0.0079) in utility was found for patients in the EFG + CT group compared to the PBO + CT group., Conclusion: Among patients with gMG, improvements in MG-ADL were significantly associated with higher utility values. MG-ADL scores alone were not sufficient to capture the utility gained from efgartigimod therapy., (© 2023. The Author(s).)

Purpose: To investigate the changes of plasma 25(OH)D levels in type 2 diabetes mellitus (T2DM) patients and explore its role in the dysfunction of glucose and lipid metabolism and cognition., Methods: One hundred and thirty-two T2DM patients were enrolled and the demographic and clinical data were collected. The plasma concentration of 25(OH)D was detected and the patients were divided into two groups including a Vitamin D insufficient (VDI) group and a normal VD group according to the clinical diagnostic criterial of VDI with the plasma 25(OH)D level less than 29 ng/mL. The glycolipid metabolic and routine blood biochemical indices were detected, the plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble myeloid soluble trigger receptor 1 (sTREM1) were measured. The cognitive function was assessed using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). The depressive symptomatology was assessed using the Center for Epidemiological Survey Depression Scale (CES-D). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI)., Results: There were 70 T2DM patients with VDI (70/132, 53.03%) in this study. The plasma concentrations of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), IL-6, and sTREM1 were remarkably increased in T2DM patients with VDI as compared with that with the normal VD, accompanied with an elevated BRIEF-A scores. There was no significant difference between groups with regard to the indices of blood lipid, liver function, and scores in CES-D and PSQI. Moreover, results of Pearson correlation test showed that the plasma 25(OH)D levels were negatively correlated with HbA1c, FPG, PBG, CRP, IL-6, sTREM1, CES-D sum scores, and PSQI sum scores, but positively correlated with the plasma levels of Serum creatinine (Scr). Furthermore, result of Receiver Operating Characteristic (ROC) curve analysis showed a predictive role of VDI levels in discriminating T2DM patients with higher cognitive impairments, with the sensitivity and specificity being 62.12% and 62.12%, respectively., Conclusion: VDI is harmful for T2DM patients with a significant relation with the hyperglycosemia and cognitive dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Yu, Gao, Wei, Qi, Ma, Xu, Xu and Ge.)

Objective: To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation., Methods: Patients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 - December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared., Results: Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation., Conclusions: Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: To examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients., Methods: Real-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers)., Results: A total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9-1641; mean/range follow-up was 10/3-24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89-1621 and 768/19-2870, respectively; mean/range follow-up was 11/6-18 and 12/6-8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%)., Conclusion: Biosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization. As such, a literature review was conducted to better understand the economic value of remission. Despite the large heterogeneity found in RA-related economic outcomes across studies, patients in remission consistently had lower direct medical and indirect costs, less healthcare resource utilization, and greater productivity compared to those without remission. Remission was associated with 19-52% savings in direct medical costs and 37-75% savings in indirect costs. The economic value of remission should thus be considered in economic analyses of RA therapies to inform treatment and reimbursement decisions., (© 2021. The Author(s).)