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Periodontal disease has significant negative effects on the health and lives of people worldwide, including chronic pain, eating difficulties, social anxiety, economic costs of treatment, and lost productivity (1). Diet is an influential factor in managing periodontal disease (2). However, it is currently unclear whether following UK healthy eating recommendations outlined in the Eatwell Guide (EWG), which is a reference used in public health initiatives and clinical practice in the UK (3), is associated with risk of periodontal disease. To address this knowledge gap, this study examined cross-sectional and prospective associations between adherence to the EWG and the risk of periodontal disease.
This study was conducted using data from the UK Biobank prospective cohort study. EWG adherence scores were created using dietary data from 24-hour dietary questionnaires (Oxford WebQ). Participants were awarded points between 0–5 reflecting the extent to which they adhered to each of the 12 healthy eating recommendations outlined in the EWG (total score range: 0-60). Periodontal disease risk markers were assessed using self-reported oral health questionnaires. Logistic regression models were used to examine cross-sectional associations between levels of EWG adherence (low, medium and high) and odds of periodontal disease. Generalised estimating equations were used to analyse prospective associations. Analyses were adjusted for relevant covariates.
Cross-sectional analyses involving 158,899 participants showed significant associations between higher (odds ratio (OR) [95% Confidence Interval (CI)]: 0.876 [0.848–0.906]) and moderate (OR [95% CI]: 0.958 [0.927–0.989]) adherence to the EWG and lower odds of periodontal disease versus the low-adherence reference group. These results were consistent with prospective analyses (higher adherence: OR [95% CI]: 0.861 [0.834–0.888]; moderate adherence: 0.943 [0.914–0.973]). Results were robust to a range of sensitivity analyses.
Following UK-specific healthy eating recommendations, as outlined in the Eatwell Guide, could help lower the risk of periodontal disease. These findings warrant substantiation in future randomised controlled trials.
Malnutrition from poor diet is a persistent issue in Sri Lanka, especially among women and children. High rates of undernutrition and micronutrient deficiencies are documented among rural poor communities(1). Household food production may enhance maternal and child nutrition directly by increasing access to diverse foods and indirectly by providing income to diversify diets(2). This study explores the cross-sectional relationship between household food production and individual dietary diversity among women aged 18-45 years and children aged 2-5 years in Batticaloa district, Sri Lanka. We randomly selected 450 low-income mother-child pairs receiving a Samurdhi subsidiary, having a home garden. Through face-to-face interview, we gathered information on the types of crops grown and livestock reared in the preceding 12 months. Production quantity and utilization were also detailed. Additionally, socio-demographic information and market access were obtained. To measure women’s dietary diversity (DD), we used a scale based on 10-food groups and a 7-food group scale for children. Women who consumed five or more food groups were defined as meeting the Minimum Dietary Diversity of Women (MDD-W), whereas children who consumed of four or more food groups met the minimum standards. Multiple linear regression and binary logistic regression were used to identify the factors predicting individual DD. Complete data for 411 pairs were analysed. The results showed, only 15.3% of the women met MDD-W, with a mean DDS of 3.3 (SD = 1.2). Children had a mean DDS of 3.3 (SD = 1.2), and 41.1% of them met the minimum diversity. Regression analysis indicated that growing leafy vegetables was positively associated with increased dietary diversity of women (β = 0.337; 95% CI: 0.13, 0.54; p = 0.001) and children (β = 0.234; 95% CI: 0.05, 0.42; p = 0.013) but not with meeting the minimum diversity. Moreover, monthly income above 35,000 LKR, higher education level, a secondary income source andfood security were also positively associated with women’s DD. Conversely, living further away from the main road reduced the women’s DD. Interestingly, livestock ownership was only associated with women meeting the MDD-W, but not for children. For children, monthly income was a strong predictor of DD and meeting minimum diversity. Surprisingly, living far from the market was associated with increased DD in children (β = 0.018; 95% CI: 0.01, 0.03; p = 0.013), while distance to main road had a similar effect as in women. Notably, selling their produce at the market contributed to meeting the minimum dietary diversity in children (β = 0.573; 95% CI: 0.14, 1.02; p = 0.013). These findings suggest that enhancing household food production could play a crucial role in improving dietary diversity and addressing malnutrition, particularly in rural Sri Lankan communities, and potentially in other similar settings.
In childhood, diets high in sodium and low in potassium contribute to raised blood pressure and cardiovascular disease later in life(1). For New Zealand (NZ) children, bread is a major source of dietary sodium, and fruit, vegetables, and milk are major dietary sources of potassium(2,3). However, it is mandatory to use iodised salt in NZ bread meaning reducing the salt and thus sodium content could put children at risk of iodine deficiency(4). Our objective was to measure the sodium, potassium, and iodine intake, and blood pressure of NZ school children 8-13 years old. A cross-sectional survey was conducted in five primary schools in Auckland and Dunedin. Primary schools were recruited between July 2022 and February 2023 using purposive sampling. Seventy-five children (n= 37 boys, 29 girls, and nine children who did not state their gender) took part. The most common ethnicity was NZ European and Other (n=54 or 72%) followed by Māori (indigenous inhabitants; n=9 or 12%) and Pasifika (n=5 or 7%). The main outcomes were 24-hour sodium and potassium intake, sodium to potassium molar ratio, 24-hour iodine intake, and BP. Sodium, potassium, and iodine intake were assessed using 24-hour urine samples and BP was assessed using standard methods. Differences by gender were tested using two-sample t-tests and nonparametric Wilcoxon two-sample tests. The mean (SD) 24-hour sodium excretion, potassium excretion, and sodium to potassium molar ratio for children with complete samples (n=59) were 2,420 (1,025) mg, 1,567 (733) mg, and 3.0 (1.6), respectively. The median (25th, 75th percentile) urinary iodine excretion was 88 (61, 122) µg per 24 hours and the mean (SD) systolic and diastolic blood pressure (n=74) were 105 (10) mmHg and 67 (9) mmHg, respectively. There was a significant difference between boys and girls for iodine (77 (43, 96) vs. 98 (72, 127) µg per 24 hours; p=0.02) but no other outcomes. In conclusion, children consumed more sodium and less potassium and iodine than World Health Organization recommendations(5). However, future research should confirm these findings in a nationally representative sample. Evidence-based, equitable interventions and policies with adequate monitoring should be considered to reduce potentially suboptimal sodium, potassium, and iodine intakes in New Zealand.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.
Methods:
Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.
Results:
Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).
Discussion:
Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.
Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.
Background: Computed tomography (CT) is common imaging modality, though its utilization of iodinated contrast media (ICM) has been historically associated with adverse effects on the kidneys including nephropathy. This study aims to investigate whether administration of ICM in critically ill patients is associated with reduced kidney function and acute kidney injury (AKI). Methods: Data was used from two prospective cohort studies- ACT-TBI and CANCCAP, where patients underwent a whole head CT perfusion with additional CT scans. Serum creatinine (CR) and glomerular filtration rate (eGFR) were sequentially collected for five days of their ICU stay. AKI was evaluated following the KDIGO criteria. Results: Of the 291 patients enrolled, a stratified trend analysis for eGFR could be conducted in 158 patients. No AKI was identified in any of these patients in our study. A significant upward trend in eGFR was observed in those older than 40 years (p=0.027), those with hypertension (p=0.027), diabetes (p=0.027) and history of smoking (p=0.027), The volume of ICM received was not significantly associated with patients’ eGFR. Conclusions: AKI was not identified in critically ill patients who received ICM but significant upward trend of eGFR was seen in older individuals and those with diabetes, hypertension, and a history of smoking.
Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
Background: Axonal degeneration has been recognized as a key early contributor to the clinical presentation and pathogenesis of amyotrophic lateral sclerosis (ALS). Activation of the calcium-dependent cysteine protease calpain-2 is considered a critical effector of axonal degeneration. Based on evidence supporting a potential benefit of calpain-2 modulation in ALS and other neurodegenerative diseases, Amylyx developed AMX0114, an antisense oligonucleotide (ASO) inhibitor of calpain-2. This phase 1 study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMX0114 in people with ALS. Methods: LUMINA is planned to be conducted at ~15 sites in North America enrolling approximately 48 participants randomized 3:1 to receive AMX0114 or placebo. After study completion, an open-label extension study of AMX0114 will be implemented if data supports a positive benefit-risk profile. Results: The primary endpoints of the study include the incidence of adverse events (AEs), serious AEs, and dose-limiting toxicities. Secondary and tertiary endpoints include PK measurements (plasma and cerebrospinal fluid [CSF] levels of AMX0114), PD biomarkers, and functional measures of ALS progression. Conclusions: LUMINA is a first-in-human study evaluating the safety, tolerability, PK, and PD of AMX0114, the first ASO targeting calpain-2 in adult participants with ALS. Enrollment is planned to begin in Canada in early 2025.
Background: TeleStroke can improve access to stroke care in rural areas. We aim to evaluate the safety and effectiveness of intravenous thrombolysis in our TeleStroke system. Methods: The Manitoba TeleStroke program was rolled out across 7 sites between November 2014 and January 2019. We retrospectively analyzed prospectively collected consecutive acute stroke patients’ data in this duration. The primary outcome was safety and effectiveness measured in terms of 90-day modified Rankin score (mRs). The number of acute ischemic stroke (AIS) patients receiving thrombolysis and endovascular thrombectomy [EVT] and process metrics were also analyzed. R/RStudio version-4.3.2 was used (p<0.05). Results: Of the 1,748 TeleStroke patients (age 71 years [IQR 58-81], female 810[46.3%]), 696 were identified as AIS. Of these, 265(38.1%) received thrombolysis and 48(6.9%) EVT. Ninety-day mortality was 53(20.0%) among those receiving thrombolysis and 117(44.2%) had a favorable outcome (mRs ≤2). Of those who received intravenous thrombolysis, 9 patients (4.2%) were found to have symptomatic intracranial hemorrhage. The median last-seen-normal (LSN)-to-door was121 minutes and the median door-to-needle, 55 minutes. Conclusions: Intravenous thrombolysis was found to be effective with acceptable safety. TeleStroke improved overall access to stroke care and played an important role in identifying AIS patients eligible for thrombolysis and EVT.
Background: Glioblastoma (GB) is the most malignant primary brain tumor. Isolated restricted diffusion (IRD) is restricted diffusion outside the confines of enhancing tumor with no corresponding enhancement on post contrast study. The aim of our study was to prospectively assess the incidence of IRD in GB patients, determine how often these foci proceed to contrast enhancement on follow up, and analyze the survival pattern. Methods: In a prospective pilot cohort study, consecutive adult patients with GB on initial MRI of brain, were included and screened for IRD. All images were independently analyzed by two experienced radiologists. The survival pattern of patients with IRD was assessed with Cox-regression and Kaplan-Meier curve analysis. Results: Of the 52 patients (median age- 63 years; male-63.5%), 21% (11 of 52) exhibited IRD. Inter-rater agreement on the diagnosis of IRD foci was fair (kappa=0.29). Seven (64%) showed enhancement in the IRD focus. The Kaplan Meier analysis revealed a significant decrease (p=0.035) in the survival was observed among patients with IRD focus. Conclusions: IRD focus was seen in 21% of patients with GB, with 64% of these demonstrating enhancement at the IRD focus on follow up imaging. A shorter survival was associated with IRD foci.
Background: Anti-CD20 monoclonal antibodies are highly effective for RMS treatment. Ocrelizumab (OCR) is standard, while Rituximab (RTX) is an alternative. The impact of anti-CD20 therapies on immune markers remains understudied, though deficiencies are frequently observed and have been associated with increased risk of infection. Our objective is to characterize and compare lymphocyte, neutrophil, and immunoglobulin levels in OCR- versus RTX-treated persons with RMS. Methods: This retrospective chart review included RMS patients on OCR or RTX (2017–2023). Pre- and post-treatment levels of lymphocytes, neutrophils, and immunoglobulins (IgG, IgA, IgM) were analyzed. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for survival analysis. Results: 350 patients (OCR=175, RTX=175) were included. The mean treatment length was 60.9 (SD 19.1) months for OCR and 42.7 (SD 19.5) months for RTX. RTX was associated with a significantly shorter time to IgM deficiency (29.6 vs. 40.0 months, p=0.02). Cox analysis confirmed RTX increased IgM deficiency risk (HR=1.54, 95% CI: 1.06-2.23, p=0.02). No differences were seen for lymphocytes, neutrophils, IgG, or IgA. Conclusions: RTX was associated with a shorter time to and increased risk of IgM hypogammaglobulinemia compared to OCR, highlighting the importance of long-term monitoring. Further research is needed to guide treatment decisions.
Background: The COVID-19 pandemic posed significant challenges for people with multiple sclerosis (PwMS) in Oman, including heightened stress, treatment disruptions, and risks associated with immunosuppressive therapies. This study aimed to evaluate the pandemic’s impact on MS management, COVID-19 incidence and outcomes, psychosocial and mental health effects, and demographic and clinical predictors influencing these outcomes among Omani PwMS. Methods: In this cross-sectional study conducted from January to April 2021, 104 PwMS aged 18–60 participated in structured interviews and completed the Expanded Disability Status Scale (EDSS) and the World Health Organization Well-being Index (WHO-5). Clinical data on relapse rates, disease-modifying therapies (DMTs), and treatment adherence were analyzed using descriptive and inferential statistics. Results: Of the participants, 76 (73.1%) were female, and 23 (22.1%) reported contracting COVID-19, with fatigue being the most common symptom (87%). Female sex (p = 0.042), younger age (18–34 vs. 35–45 years; p = 0.014), COVID-19 diagnosis (p = 0.037), and lower mental well-being scores (p = 0.021) were strongly associated with COVID-19-related effects. Conclusions: Key predictors of self-reported COVID-19 effects in Omani PwMS were a confirmed diagnosis, female sex, younger age, and lower mental well-being. These findings highlight the need for exploration of mental resilience in this group and interventions during crises.
Background: Generalized myasthenia gravis (gMG) is a potentially life threatening chronic autoimmune disease that can impair patients’ ability to work effectively and increase reliance on public support benefits. A public economic framework was used to explore how treatment influences patients’ and caregivers’ economic activity, including tax revenues and public support in Canada. Methods: Natural history of gMG was simulated using a multi-state Markov cohort model. Health states were based on MG Activities of Daily Living (MG-ADL) total score in patients with AChR-Ab+ refractory gMG. Treatment, costs, and economic outcomes of patients taking efgartigimod were compared with alternative therapeutic options. Canadian public support benefits were based on official government sources. Results: Improved MG-ADL states predict higher workforce participation, lower rates of disability and less caregiving needs, resulting in higher tax revenues and less public support costs. Compared to alternative therapeutic options, efgartigimod is estimated to yield lifetime fiscal gains of $458,755 that exceed the incremental cost of $291,073, suggesting the Canadian government receives $1.6 for every $1.0 spent on efgartigimod for the treatment of gMG. Conclusions: Compared with alternative options, efgartigimod generated a positive fiscal return for the Canadian governments with additional savings from disease management, public benefits, and averted tax revenue losses.
Background: Anterior (ACS) and posterior circulation (PCS) stroke patients have different clinical presentations and prognoses, though both benefit from endovascular thrombectomy (EVT). We sought to determine whether ACS and PCS patients treated with EVT differed with regards to treatment metrics and functional outcomes. Methods: We retrospectively analysed theCanadian OPTIMISE registry which included data from 20 comprehensive stroke centers across Canada between January 1, 2018, and December 31, 2022. We performed a descriptive analysis of patients divided in two groups (ACS= carotid artery and its branches, PCS= vertebrobasilar system). Results: Of the 6391 patients included (5929 ACS and 462 PCS), PSC patients were younger (67 vs. 71.3, p<0.001), more often male (61.9% vs. 48.6%, p<0.001), had longer (in minutes) onset-to-door (362 vs. 256, p<0.001), door-to-needle (172 vs. 144, p=0.0016), and onset-to-puncture (459 vs. 329, p<0.001) times. They were less often thrombolyzed (39.8% vs. 50.4%, p<0.001), and more frequently underwent general anesthesia (47.6% vs. 10.6%, p<0.001). Successful reperfusion and functional independence at 90 days were similar between the two groups. Conclusions: Patients with PCS had worst treatment metrics than ACS. Strategies to improve PCS management times are critical to decrease these disparities, including faster pre-hospital recognition and in-hospital workflows.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.