Antibody Status Research Articles

Hippocampal dysfunction after autoimmune encephalitis depending on the antibody type.

Comprehensive neurocognitive function analyses of autoimmune encephalitis (AE) patients, especially long-term ones, are rare. This study aims to measure cognitive function in patients diagnosed with AE. This case-control study included AE patients (n = 11) with antibodies against NMDA receptor (NMDAR) (n = 4), VGKC (n = 3), GAD (3), and one antibody-negative patient. The control group contained 12 pneumococcal meningo-encephalitis patients (PC). Subgroup analyses compared AE patients with and without NMDAR antibodies. Neurocognitive tests were performed to evaluate verbal and visual memory, face recognition, attentional capacity, incidental learning capacity, and overall cognitive function (Montreal cognitive assessment, MoCA). Limbic structural involvement was assessed through magnetic resonance imaging (MRI). Statistical analyses investigated correlations between antibody status, results of neurocognitive tests, and MRI findings. Follow-up (AE vs. PC) was 33 (11-95) vs. 96 (26-132) months after diagnosis. Neurocognitive functions were normal in both AE and PC groups in all tests except face recognition, which was pathological in both groups. The overall/recognition/long-delay visual memory (p = 0.009/0.008/0.005) and incidental learning (p = 0.017) scores were significantly higher in NMDAR patients compared to non-NMDAR patients. Non-NMDAR patients with right-sided limbic MRI pathologies had significantly lower overall/recognition/long-delay visual memory (p = 0.006/0.044/0.024) and incidental learning (p = 0.009) scores compared to NMDAR patients. We observed mainly normal neurocognitive functions after autoimmune and bacterial encephalitis. However, compared to NMDAR patients, patients with non-NMDAR autoimmune encephalitis showed a significant and material-specific association between a right-sided hippocampal lesion and limitations in figural-mnestic and incidental learning capacities. Neurocognitive functions in AE patients should be further evaluated prospectively and in more detail.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia-Pacific, Europe, and North America. Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region. The sponsor, investigators, clinical raters, and participants were masked to treatment assignment. The primary endpoint was the difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL total score averaged over weeks 22, 23, and 24 in the intention-to-treat population of patients who were antibody-positive (for AChR, anti-muscle-specific tyrosine kinase [MuSK], or anti-low-density lipoprotein receptor-related protein 4 [LRP4]). Adverse events were assessed in patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT04951622; the double-blind phase is completed and an open-label extension phase is ongoing. Between July 15, 2021, and Nov 17, 2023, 199 patients were enrolled, and 196 patients received study drug (98 in the nipocalimab group and 98 in the placebo group); of these, 153 (77 in the nipocalimab group and 76 in the placebo group) were antibody-positive. The least-squares mean change in MG-ADL score from baseline to weeks 22, 23, and 24 was -4·70 (SE 0·329) in the nipocalimab group versus -3·25 (0·335) in the placebo group (difference -1·45 [95% CI -2·38 to -0·52]; p=0·0024). The incidence of adverse events was similar between groups (82 [84%] of 98 in both the nipocalimab and placebo groups), including infections (42 [43%] of 98 in the nipocalimab group and placebo group) and headache (14 [14%] of 98 in the nipocalimab group and 17 [17%] of 98 in the placebo group). Serious adverse events were reported for nine (9%) of 98 patients in the nipocalimab group and 14 (14%) of 98 patients in the placebo group, three of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction). Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive. The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab. Janssen Research & Development, LLC, a Johnson & Johnson company.

Comparing three different platforms for the testing of intrinsic factor antibody and cross correlation with gastric parietal cell antibody status, in the diagnosis of pernicious anaemia

Comparing three different platforms for the testing of intrinsic factor antibody and cross correlation with gastric parietal cell antibody status, in the diagnosis of pernicious anaemia

A protocol for pretreatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions.

115 Background: Cetuximab has been shown to improve survival in patients with KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20%. A major driver of cetuximab HSR is from pre-formed antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. We are the first to report on the impact of prospective alpha-gal antibody screening on cetuximab HSR. Methods: Records were reviewed across three medical oncology centres that have adopted alpha-gal antibody screening measures. Data for patients with metastatic colorectal cancer treated with cetuximab were retrieved. All centres assessed alpha-gal antibody status using the ImmunoCAP ELISA assay. Due to lack of a shared screening approach across study sites, a pre-determined protocol was retrospectively applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.1 kUA/L, but prohibited it if alpha-gal levels were >0.1 kUA/L in favour of panitumumab administration. Patients were allocated to either the Protocol Applied or Protocol Not Applied cohorts based on protocol requirements being met. The primary outcome between these patient groups was the incidence of cetuximab HSRs. Results: Of 254 assessable patients, 39 underwent the pre-treatment screening protocol. Of the Protocol Applied group, 3% (n=1/38) experienced a cetuximab HSR compared to 16% (n=35/215) in the Protocol Not Applied group (Odds ratio (OR) 7.16; 95% CI 1.13–299.61, p =0.02). Patients with alpha-gal antibody titres >0.1 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18–4296.81, p =0.0001). Conclusions: Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.1 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations.

P-1928. Virologic and Clinical Outcomes Among Participants Hospitalized in a Phase 3 Trial Comparing Molnupiravir with Placebo for Treating Mild-to-Moderate COVID-19

Abstract Background The correlation between virologic and clinical outcomes in COVID-19 remains unclear. The objective of this analysis was to assess SARS-CoV-2 viral load (VL) and laboratory biomarkers in participants who did and did not progress to hospitalization in the phase 3 component of the MOVe-OUT trial.Table 1.Baseline demographics and characteristics of participants who did and did not progress to hospitalization*One participant in the placebo group with an unknown hospitalization status was not included in this analysis. Methods In MOVe-OUT, unvaccinated adults with mild-to-moderate COVID-19 at risk for disease progression were randomized 1:1 to molnupiravir (MOV) 800-mg or placebo (PBO) every 12 hours for 5 days. The primary efficacy endpoint was all-cause hospitalization or death through day 29. In this analysis, the following were evaluated in the modified intent-to-treat (MITT; randomized, received ≥1 dose of study drug, and not hospitalized prior to 1st dose) population (1408 participants) at baseline and at postbaseline time points: VL (quantitative PCR), high-sensitivity C-reactive protein (CRP), and absolute lymphocyte count (ALC).Figure 1.Mean change in SARS-CoV-2 viral load in hospitalized and non-hospitalized participants (A) and SARS-CoV-2 viral load over time in hospitalized participants (B)Hospitalization ± 48 hours excluding baseline.One participant in the placebo group with an unknown hospitalization status was not included in this analysis. Results 115 (8.2%) participants progressed to hospitalization (HP). HP were more likely vs those who remained non-hospitalized (NHP) to be male; ≥65 years; with active cancer, diabetes mellitus, moderate COVID-19, and negative nucleocapsid and neutralizing antibody status at baseline (Table 1). Mean time from symptom onset to hospitalization, and randomization to hospitalization, was 8.9 and 5.3 days. In HP, mean VL at baseline was 7.51 vs 6.83 log10 copies/mL among NHP. Among HP, VL declined in 37/38 (97.4%) MOV and 50/63 (79.4%) PBO-treated participants, respectively, between baseline and the day of hospitalization. Mean decline in VL from baseline to day 5 was 1.90 (SD 1.53) in HP vs 2.12 (SD 1.62) log10 copies/mL in NHP, with greater declines observed in MOV vs PBO-treated participants at all time points (Figure 1). Mean CRP was higher at baseline in HP vs NHP (49.93 vs 16.77 mg/L), and postbaseline values increased in HP and decreased in NHP. Alternatively, mean ALC was lower at baseline in HP vs NHP (1.07 vs 1.54 109/L), and postbaseline values continued to decrease at day 3 and 5 in HP while values increased in NHP (Table 2).Table 2.Mean change in C-reactive protein and absolute lymphocyte count in hospitalized and non-hospitalized participantsHospitalization ± 48 hours excluding baseline. Conclusion HP had a higher VL at baseline, with a smaller decline over time than NHP. A higher VL at baseline in conjunction with an increasing CRP and decreasing ALC may help identify patients with mild-to-moderate COVID-19 at higher risk for hospitalization. Disclosures Matthew G. Johnson, MD, Merck & Co., Inc.: I have an interest in a patent application for the company.|Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) David W. Hilbert, PhD, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Erin Jensen, MS, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Dorothy McCoy, PharmD, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Brian Maas, PharmD, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Ying Zhang, PhD, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Michelle L. Brown, BS, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Dana L. Byrne, MD, Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company) Carisa S. De Anda, PharmD, Merck & Co., Inc.: MOV patent|Merck & Co., Inc.: Employee of Merck & Co., Inc.|Merck & Co., Inc.: Stocks/Bonds (Public Company)

Limited Utility of Routine Surveillance Ultrasound in Differentiated Thyroid Cancer Patients With Undetectable Postoperative Thyroglobulin Levels.

Neck ultrasound (US) and serum thyroglobulin (Tg) measurements are mainstays of long-term differentiated thyroid cancer (DTC) surveillance. Given the high sensitivity of serum Tg, we aimed to assess the utility of neck US in DTC patients who underwent total thyroidectomy and have undetectable serum Tg. We performed a retrospective cohort analysis of DTC patients who underwent a total thyroidectomy at our institution (2010-2023) and received US-guided fine needle aspiration (FNA) during their surveillance. Patients were categorised into three lab categories based on serum Tg and Tg antibody (Tg Ab) status before the biopsy: (1) 'Negative Tg' if undetectable Tg ( < 0.2 ng/dL) and Tg Ab, (2) 'Positive Tg' if detectable Tg and undetectable Tg Ab, and (3) 'Positive Tg Ab' if detectable Tg Ab. To calculate the positive predictive value (PPV) of neck US, we defined the 'true positive' of US as findings that prompted an FNA biopsy resulting with DTC, and 'false positive' findings prompting an FNA biopsy that did not result as DTC. A total of 118 patients were included, encompassing 146 FNA biopsies: 33 (23%) had Negative Tg, 84 (57%) had Positive Tg, and 29 (20%) had Positive Tg Ab lab results before their biopsies. The PPV of neck US in the setting of Negative Tg was 3% (one true positive, 32 false positives), while the PPV was 50% (42 true positives, 42 false positives) for Positive Tg, and 52% (15 true positives, 14 false positives) for Positive Tg Ab cohorts. Sub-analysis of the Positive Tg cohort using different serum Tg level cutoffs revealed a PPV of 29% at just detectable serum Tg of 0.2 ng/dL, and PPV of 38% for Tg < 1.0 ng/dL. The PPV stabilised at 58% for Tg levels ≥ 1 ng/dL. With the low PPV of neck US, high cost of surveillance, and the advent of ultra-sensitive serum Tg measurements, future guidelines should consider reducing routine neck US surveillance in patients with undetectable serum Tg and only performing it when there is a rise in serum Tg levels.

P0755 Long-term safety of subcutaneous vedolizumab in Ulcerative Colitis and Crohn’s disease: Findings from the VISIBLE OLE study

Abstract Background Vedolizumab (VDZ) is a gut selective, monoclonal anti-α4β7 integrin antibody approved for the treatment of moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) and is available in subcutaneous (SC) formulation. This analysis assessed the long-term safety outcomes of specific interest to the SC formulation of VDZ. Methods Patients (pts) who participated in VISIBLE 1 or VISIBLE 2 were eligible to enrol in VISIBLE OLE (NCT02620046). In VISIBLE 1, pts with UC were treated with placebo, VDZ SC or VDZ intravenous (IV). In VISIBLE 2, pts with CD were treated with placebo or VDZ SC. In VISIBLE OLE, pts received VDZ SC 108mg every 2 weeks (Q2W) or weekly. Pts received training on SC administration, and most injections were conducted at home by pt or caregiver. Safety of VDZ SC included assessing anti-VDZ antibody (AVA) status and injection site reaction (ISR) adverse events. Blood specimens for AVA assessment were collected 30 minutes before dosing every 16 weeks, at the final dose and the final safety visit 18 weeks after last dose. Data were assessed by treatment pts received during VISIBLE 1 and 2. Results Overall, 288 pts with UC and 458 pts with CD enrolled in VISIBLE OLE. A mean of 91.1 and 74.2 SC injections were completed by pts with UC and CD, respectively, during the OLE. Among pts with UC, the positive AVA rate was higher in pts previously treated with placebo (17.3%) than those treated with VDZ SC (3.4%) or IV (2.6%) (Table 1). The positive AVA rate was also higher among pts with CD previously treated with placebo (11.4%) than with VDZ SC (1.8%). A total of 14/288 pts (4.9%) with UC reported ISRs (Table 2), most of which were mild and none were serious. Two pts developed moderate ISRs; neither required dose modification and both were resolved. Overall, 19/458 pts (4.1%) with CD reported ISRs (Table 2). The majority of ISRs were mild, 2 were moderate and none were severe, and none required dose modification. No direct correlation between AVA status and ISRs was identified, with 11/14 pts (78.6%) with UC and 17/19 pts (89.5%) with CD who reported ISRs being AVA negative. All 5 pts who were AVA positive and reported an ISR had previously received placebo. The highest rate of ISRs were in pts who received placebo in VISIBLE 1 (13.5%). Conclusion No new long-term safety events were identified with the VDZ SC route of administration compared to IV, except for ISRs. A higher proportion of patients who had previously been treated with placebo than those treated with VDZ during VISIBLE 1 and 2 were AVA positive during VISIBLE OLE, supporting a benefit of continued therapy with VDZ SC after IV induction, rather than cessation of treatment for a period of time.

Cutaneous ulceration in dermatomyositis : Case reports with positive anti-NXP-2/anti-TIF1-gamma antibody status

Painful ulcerations developed in a33-year-old woman with anti-NXP-2-positive dermatomyositis in the facial and trunk areas and a 67-year-old woman with TIF1-gamma-positive dermatomyositis on the hands, while undergoing systemic therapy with azathioprine or low-dose methylprednisolone and cyclic administration of intravenous immunoglobulins (IVIG), respectively. In the laboratory workup, the anti-MDA‑5 antibody status remained negative and the creatine kinase (CK) normal in both patients, while histopathological examinations were nonspecific. Intensive topical class4 corticosteroid therapy and continuation of the immunosuppressive or immunomodulating therapy led to healing of the ulcerative skin lesions. This report aims to raise awareness of the rare occurrence of cutaneous ulceration in anti-NXP-2- or anti-TIF1-gamma-positive dermatomyositis, as ulcerations may be associated with a severe disease course. In both of our patient cases, it is exclusively adermal manifestation without other complications.

Association between antinuclear antibodies status and preterm birth in Japanese pregnant women: a prospective cohort study from Adjunct Study of the Japan Environment and Children’s Study

BackgroundAntinuclear antibodies (ANA) are important biomarkers for the diagnosis of autoimmune diseases; however, the general population also tests positive at a low frequency, especially in women. Although the effects of various autoimmune diseases on pregnancy outcomes have been studied, the association of ANA with pregnancy outcomes in healthy individuals is unclear. Preterm birth (PTB), a major cause of neonatal death or long-term health problems, is a complex condition with a multifactorial etiology, and the underlying mechanism remains unclear. The present Adjunct Study aimed to determine the association between ANA and PTB in pregnant Japanese women based on a data analysis of the Japan Environment and Children’s Study.MethodsIn a prospective cohort design, we analyzed the demographic and pregnancy outcome data of 1085 pregnant Japanese women who were recruited between January 2011 and March 2014 in the Kumamoto University target area. Demographic data were collected using self-administered questionnaires and physician records. A serum ANA titer of ≥ 1:40 was defined as positive. Statistical analysis was performed by logistic regression analysis with PTB as the objective variable.ResultsThe PTB rate was significantly higher in those who were ANA-positive (adjusted odds ratio, 2.06; 95% confidence interval, 1.09–3.87) than in those who were not.ConclusionsThis study suggests that ANA positivity in the first trimester of pregnancy is associated with an increased risk of PTB.

Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE® NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL. Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL. A wide range of subcutaneous epcoritamab doses, 0.004-60 mg, was explored, with most patients (n = 298) following the approved dosing regimen: step-up dose (SUD) 1 of 0.16 mg on cycle 1 day 1 and SUD 2 of 0.8 mg on cycle 1 day 8, followed by a full dose of 48 mg administered weekly during cycles 1-3, biweekly in cycles 4-9, and every 4 weeks thereafter. Each cycle lasted 28 days. The data were analyzed using nonlinear mixed-effects modeling. Quasisteady-state approximation of a two-compartment target-mediated drug disposition model with first-order absorption adequately characterized pharmacokinetics of epcoritamab following subcutaneous administration. After the first full dose and at the end of the weekly dosing regimen (end of cycle 3), the estimated median time to maximum concentration (tmax) was 4 and 2.3 days, respectively. Age and body weight were significant covariates on the pharmacokinetics of epcoritamab. The geometric mean (coefficient of variation [CV], %) of the apparent total volume of distribution was 25.6 L (82%) for patients with R/R large B cell lymphoma in EPCORE NHL-1. Epcoritamab elimination exhibited nonlinear characteristics, with exposure increasing more than proportionally over 1.5-48 mg doses. The geometric mean (CV%) values of apparent total clearance and terminal half-life were 0.53 L/day (40%) and 22 days (58%), respectively, at the end of cycle 3 for the 48 mg full dose. Clinical data analyses did not identify any association between assessed characteristics, including body weight or age, and clinical efficacy or safety. After accounting for body weight, no clinically significant differences in epcoritamab pharmacokinetics were observed for sex, race, renal or hepatic function, or other disease characteristics. Age was not found to significantly affect epcoritamab pharmacokinetic exposure. Antidrug antibodies developed in 4 (2.6%) of 156 evaluable patients treated with the approved 0.16/0.8/48 mg regimen. Antidrug antibody status did not affect epcoritamab pharmacokinetics. Epcoritamab pharmacokinetics in R/R B-NHL were well characterized by the population pharmacokinetic model. No dosage adjustments are recommended in subpopulations based on body weight, age, sex, race, mild-to-moderate renal impairment, or mild hepatic impairment. The risk of immunogenicity was low. These are the first published results of population pharmacokinetic modeling for epcoritamab.

Epidemiological Survey of Canine Distemper Virus Infection: Exploring the Link Between Virus Spread and Invasive Raccoon (Procyon lotor) Population Growth in Hokkaido, Japan

ABSTRACTInvasive raccoons (Procyon lotor) naturalized in Hokkaido, Japan, potentially spreading infectious diseases. Canine distemper virus infection is a serious epizootic disease, for which the raccoon is one of the hosts. We investigated the virus's prevalence in Hokkaido's wild raccoons, using 611 serum samples collected from captured raccoons in 2007–2012, 2021, and 2022. Higher seropositivity rates were confirmed in 2007 (32.7%), 2021 (46.4%), and 2022 (46.8%) than in 2008–2012 (0.00%–6.06%), suggesting the occurrence of an epidemic in 2007, 2021, and 2022 and its disappearance in 2008–2012. However, the infection status has recently changed, with high seropositivity rates consecutively confirmed in 2021 and 2022. Logistic regression analysis was performed to investigate the relationships among the catch per unit effort (an index of animal population density), host and environmental factors, and antibody status. The catch per unit effort correlated with seropositivity in 2007. As for environmental factors, the forest area ratio had a weak influence on seroprevalence in 2007; however, the residential area ratio had a clear influence on seroprevalence in 2021 and 2022. The epidemic occurred in forested areas in 2007; nonetheless, recent raccoon population growth and habitat expansion may have caused widespread infections even around residential areas in 2021 and 2022. Continuous monitoring of the infection and reinforcement of raccoon control programs are necessary to avoid serious damage through disease transmission to sympatric native raccoon dog (Nyctereutes procyonoides) and fox (Vulpes vulpes) populations, as well as health consequences for domestic dogs (Canis familiaris).

Thrombocytosis and Thrombocytopenia in Treatment-Naïve Rheumatoid Arthritis Patients: A Single-Centre Retrospective Data-Based Study From Pakistan.

Background and objective This study aims to investigate thrombocytosis and thrombocytopenia in treatment-naïve rheumatoid arthritis (RA) patients, addressing the lack of data on their prevalence and clinical significance. By focusing on untreated patients, this study seeks to clarify the disease's natural course without confounding factors from prior therapies. The research is particularly important in the Pakistani context, where regional variations in RA presentation are underexplored. Findings are expected to enhance understanding of these hematological changes, ultimately guiding improved clinical management strategies for RA. Methods The present retrospective data-based study was conducted at the Department of Medicine & Allied Health Sciences, Azra Naheed Medical College, Superior University, Lahore, Pakistan. The 2010 American College of Rheumatology (ACR) diagnostic criteria were used to define RA. Thrombocytosis was defined as a platelet count greater than 400×109/L. Thrombocytopenia was defined as a platelet count less than 150×109/L. The Disease ActivityScore in 28 joints (DAS-28 score) was used to categorize the disease severity of RA. Retrospective data were collected from the medical records of 165 patients with RA. Records from January 2023 to December 2023 were included. The assessment included demographic information, rheumatoid factor status, anti-CCP antibody status, disease severity measured by the DAS-28 score, and complete blood count (CBC) results, such as hemoglobin, white blood cell (WBC) count, and platelet count. Data entry and analysis were conducted using IBM SPSS Statistics software, version 23 (IBM Corp., Armonk, NY). Results The mean age of the patients was 42.5±13.6 years, with 25 (15.2%) male and 140 (84.8%) female patients. The RA factor (RAF)was positive in 128 (77.6%) and the anti-CCP antibody in 102 (61.8%). The mean DAS-28 score was 4.5±1.4, with 113 (68.5%) patients having mild-to-moderate disease and 52 (31.5%) patients having severe disease. Mean hemoglobin, WBC, and platelet counts were 12.0±1.4 g/dl, 9.0±2.7 ×109/L, and 352.6±110.4 ×109/L, respectively. Thrombocytosis was seen in 52 (31.5%) patients, while thrombocytopenia was seen in 11 (6.7%). Conclusion Thrombocytosis was seen in almost one-third of RA patients, having a significant association with age, the RAF factor positivity, and anti-CCP antibody negativity but not with gender and disease severity. Thrombocytopenia was relatively uncommon.

Sexual behaviours and risk of SARS-CoV-2 infection among MSM during the first COVID-19 lockdown

BackgroundThe social distancing measures associated with the COVID-19 pandemic had far reaching effects on sexual behavior worldwide. However, it remains unclear whether sexual contact with non-steady partners was a contributor to the spread of SARS-CoV-2. The aim of this study was to (i) describe risk factors for SARS-CoV-2 seropositivity after the first pandemic wave among people using HIV Pre-Exposure Prophylaxis (PrEP) in Zurich, Switzerland, including sexual contact with non-steady partners, and (ii) assess whether the SARS-CoV-2 seropositivity among PrEP users in this time period differed from that of a demographic matched population level comparison group.MethodsThe study was conducted between July 2020 and October 2020 as a nested cross-sectional study within two ongoing cohort studies, SwissPrEPared (all eligible PrEP users in Switzerland ≥ 18 years old) and Corona Immunitas (a series of cross-sectional and longitudinal studies measuring the SARS-CoV-2 seroprevalence across Switzerland, beginning in April 2020). All SwissPrEPared participants were recruited from Checkpoint Zurich (the main PrEP clinic in Zurich) and were men having sex with men or transgender women. Data were collected on participants’ SARS-CoV-2 antibody status, social characteristics and behavioral data after the first wave of the pandemic in Switzerland, and seroprevalence was compared with a propensity score-matched sample from the general Zurich population.ResultsOf the 218 participants enrolled, 8.7% (n = 19, 95% CI: 5.5–13.5%) were seropositive for SARS-CoV-2 during the first pandemic wave, higher than that of the general male population in Zurich aged 20–65 (5.5%, 95% CI: 3.8–8.2%). Participants on average reduced their social outings, but the seronegative were more socially active before, during, and after the first lockdown period. In a logistic model, increasing mean sexual partner count was not associated with seropositivity (OR: 1.02, 95% CI: 0.95, 1.07). The estimated risk ratio for seropositivity for the participants compared to the general Zurich population after propensity score matching was 1.46 (95% CI: 0.53, 3.99).ConclusionsOur study suggests that SARS-CoV-2 seropositivity was slightly elevated among people taking PrEP in Zurich during the first wave of the pandemic, but that socializing and sexual activity were less important than other factors in contributing to risk.

Knowing the Antibody Status may influence compliance of health care workers to COVID-19 booster dose

Abstract Background Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high level antibody after the 3rd dose may reduce compliance to the 4th booster dose among health care workers. Methods We conducted a prospective cohort study among health care workers vaccinated with the first three doses at Rambam Healthcare Campus, a tertiary hospital in northern Israel. Participants underwent a serological test before the 4th booster vaccine was offered to all of them, with results provided to participants. The population was divided into two groups: those with antibody below 955 AU/ml, and those with 955 AU/ml and higher, a cutoff found protective in a previous study. Multiple logistic regression was carried out to compare the compliance to the 4th booster between the two groups, adjusted for demographic and clinical variables. Results After adjusting for the confounding variables, the compliance was higher in those with antibody levels below 955 AU/ml (OR = 1.41, P = 0.05, 95% CI 1.10-1.96). In addition, male sex, and age of 60 years and above were also associated with higher vaccination rate (OR = 2.28, P &amp;lt; 0.001, 95% CI 1.64 - 3.17), (OR = 1.14, P = 0.043, 95% CI 1.06 - 1.75), respectively. Conclusions Knowledge of the antibody status may affect compliance with the booster dose. Considering waning immunity over time, reduced compliance may affect the protection of health care workers who declined the 4th dose. Key messages • Knowing the antibody status may affect compliance of health care workers with the booster dose. • Reduced compliance of health care workers may affect their protection.

Relationships Among COVID-19-Related Service Uptake, HIV Status, Drug Use, and COVID-19 Antibody Status Among HIV Testing Intervention Participants in KwaZulu-Natal, South Africa.

People living with HIV (PLWH) and people who use drugs are vulnerable populations who may face barriers to accessing health services and may have irregularities in immune function. People with undiagnosed HIV infection may be particularly likely to have compromised immune function. However, research about whether/how HIV status is related to COVID-19-related health outcomes has been equivocal, and research on the predictors of COVID-19-related health service access/uptake has been limited in Sub-Saharan African settings. Among 470 participants of a peer-recruitment-based HIV-testing intervention in KwaZulu-Natal, we examined whether HIV status and/or hard drug use were associated with uptake of COVID-19 testing and vaccination, and whether they moderated the relationship between COVID-19 vaccination status and COVID-19 IgG antibody status. Women were significantly more likely than men to report testing for COVID-19 (OR = 1.84; p = 0.002) and being vaccinated (OR = 1.79; p = 0.002). Neither HIV status nor drug use was associated with likelihood of getting tested or vaccinated. Vaccinated participants (90% of whom obtained vaccines more than 6 months before the study) were significantly more likely to test positive for COVID-19 IgG antibodies (OR = 6.86; p < 0.0005). This relationship held true for subgroups of PLWH and participants with previously undiagnosed/uncontrolled HIV infection, and was not moderated by HIV status or hard drug use. These findings may suggest that both people who use drugs and PLWH were served as well as other people by KwaZulu-Natal's COVID-19 response. However, gender-based disparities in COVID-19 service uptake suggest that special care should be taken during future COVID-19 outbreaks or other new epidemics to improve access to related healthcare services among men in this region.

Efgartigimod treatment for generalized myasthenia gravis: a single-center case series of 16 patients.

Efgartigimod was approved in Japan in January 2022 for the treatment of generalized myasthenia gravis (gMG), regardless of antibody status. This case series describes a real-world experience in Japan of efgartigimod treatment for gMG patients with diverse backgrounds. We retrospectively analyzed the medical records of 16 Japanese patients (11 females and five males, mean age 40.4 years) with gMG who received efgartigimod at the Kumamoto University Hospital between August 2022 and September 2023. The outcomes were Quantitative Myasthenia Gravis (QMG) responders (≥ 3 point reduction), IgG levels, and change in prednisolone dose, in the first cycle of efgartigimod. Fifteen patients completed one cycle of efgartigimod. Of the 14 patients for whom QMG scores were obtained, 10 patients were QMG responders. Four of the five patients with Myasthenia Gravis Foundation of America class V were QMG responders. Improvement in QMG after efgartigimod treatment was observed in one patient with myasthenic crisis and in one refractory patient who had unsuccessful eculizumab treatment. The mean reductions from baseline in IgG levels at weeks 1, 2, 3, and follow-up were 38.3, 56.1, 63.1, and 43.9%, respectively. A decrease in prednisolone dose was observed in seven patients. The most common adverse events were headache (three patients) and diarrhea (two patients). One patient discontinued efgartigimod treatment due to a treatment-related adverse event of rash. Improvements in the outcomes of patients with gMG, including patients with severe gMG, myasthenic crisis, and refractory to anti-complementary therapy, were observed after the first cycle of efgartigimod treatment. Our real-world experience in Japan suggests the future possibilities for the treatment with efgartigimod for gMG with diverse backgrounds.

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and &amp;gt;5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age &amp;lt;18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

12233 Weight Gain Following Thyroidectomy For Benign Conditions

Abstract Disclosure: A. Krueger: None. A. Chiu: None. S. Pabich: None. S. Syed: None. A. Poloju: None. S. Holoubek: None. Background: Weight gain is a common complaint of patients with hypothyroidism irrespective of etiology that causes dissatisfaction and decreased quality. Patients often report thyroidectomy as the precipitating event leading to subsequent weight gain and resistance to weight loss. Reported data on body weight changes following surgery are conflicting and there is limited literature on patients with benign pathologies. The average weight gain in the general population has been reported as 0.5/year. The primary outcome of this study was to determine if patients undergoing thyroidectomy for benign conditions experienced greater than expected weight gain compared to the general population when TSH values were controlled. Secondary outcomes assessed were whether pre-operative disease pathology or antibody status affected weight changes. Methods: A retrospective review was performed on 325 patients undergoing total thyroidectomy for benign conditions from January 2015 to December 2020 using the University of Wisconsin Thyroid Surgery Database. The weight change was determined from the time of surgery to the following intervals: 1-2 years, 2-5 years, and &amp;gt;5 years. Study groups were then compared by pathology and presence of antibodies. Exclusion criteria included age &amp;lt;18 years, thyroid cancer, pregnancy within one-year post-surgery, incomplete weight or TSH data, post-operative gastric-bypass surgery, and patients who were not euthyroid pre- and post-op. Results: Our patient population (n=219) gained a mean of 1.58 kg at the 1-2 year interval. There was no significant difference in weight gain based on pathology or antibody status. At the 2-5 year interval, the average weight gain was 2.05 kg and those with antibodies had significantly higher weight gain. Patients with TPO antibodies (n=34) gained a mean weight of 4.58 kg, and those with TRAB and or TSI antibodies (n=17) gained a mean weight of 4.67 kg. Those with both types of antibodies (n=10) did not have any significant weight gain. Conclusion: Conservatively, the expected weight gain of the general population over 2-5 years is 2.5 kg. Using a logistic regression model, patients with autoimmune thyroid disease had twice the odds of gaining more weight than expected by 2-5 years. The presence of auto-immune thyroid antibodies may serve as a target population for intensive weight management programs following surgery. Presentation: 6/1/2024

7454 Angiotensin AT1 Receptor Type 1 (AT1) Autoantibodies In Patients with Primary Aldosteronism

Abstract Disclosure: J.K. Waraich: None. G. Kline: None. M.Y. Choi: None. R.J. Sigal: None. C. Caughlin: None. S.J. Przybojewski: None. A. Leung: None. Background: Primary aldosteronism (PA) is a condition characterized by excessive aldosterone secretion, and accounts for at least 10% - 20% of all cases of hypertension. Determination of PA subtype (i.e., unilateral vs. bilateral aldosterone hypersecretion) is clinically important to inform targeted treatment. We hypothesized that pathogenesis of PA is immune-mediated and autoantibodies to angiotensin receptor type 1 (AT1) may determine PA subtype. Aims: The aim of this study was to examine whether AT1 autoantibodies predict PA subtype. Methods: We conducted a cross-sectional study of patients with PA who were referred for adrenal vein sampling (AVS) for subtyping. AT1 autoantibody titres were measured using an enzyme-linked immunosorbent assay. AT1 antibodies were defined as present when the titre was &amp;gt;17 U/mL, negative if &amp;lt;10 U/mL, and indeterminate if between 10-17 U/mL. AVS was used as a gold standard to determine lateralization and PA . The frequency of positive AT1 autoantibodies was determined according to PA subtype and clinical predictors of lateralization. Baseline patient characteristics were reported as means (and standard deviations) for normally distributed variables, and medians (and interquartile ranges) for non-normally distributed variables. Fisher’s exact test was performed for categorical variables and Kruskal-Wallis test for continuous variables. Results: 54 patients had successful cannulation of both adrenal veins (mean age, 52.7 years; 46.3% male; mean body mass index, 31.2 kg/m2). AT1 antibodies were detected in 14 (25.9%) of the patients, absent in 32 (59.3%), and indeterminate in 8 (14.8%). Among the 25 patients with unilateral PA, 8 (32.0%) had positive AT1 antibodies, 15 (60.0%) negative, and 2 (8.0%) indeterminate. Similarly, among the 29 patients with bilateral PA, 6 (20.7%) had positive AT1 antibodies, 17 (58.6%) negative, and 6 (20.7%) indeterminate. There was no significant association detected between AT1 antibody status and lateralization (p=0.39). There were no associations between AT1 autoantibody status and any of the clinical factors traditionally predictive of PA, including sex (p=0.94), older age (p=0.76), hypokalemia (p=0.91), higher estimated glomerular filtration rate (p=0.46), or magnitude of aldosterone-to-renin ratio elevation (p=0.58). There was also no association between AT1 titres and these factors. Conclusion: AT1 autoantibodies are common in patients with PA; over a quarter of patients who underwent AVS in our study. Although they were not predictive of PA subtype, these results may still suggest that PA is immune-mediated. Future studies comparing AT1 autoantibodies in PA to other controls are underway. Presentation: 6/1/2024

No sex-based differences in odds of starting or time to treatment of generalized myasthenia gravis: A single center cohort study.

Females with generalized myasthenia gravis (gMG) report lower quality of life (QoL) and have more severe disease than males. Sex differences in disease characteristics exist, however whether there are sex differences in the treatment of gMG that may contribute to QoL disparities is unknown. Our objective is to determine whether there are sex differences in the treatment of gMG. We performed a single-center retrospective study of people diagnosed with gMG at the University of Calgary between 1997 and 2021. Primary outcome was proportion starting treatment and secondary outcome was time from diagnosis to treatment initiation. Treatments included pyridostigmine, prednisone, steroid sparing therapies (azathioprine, mycophenolate mofetil [MMF], methotrexate [MTX], or tacrolimus), intravenous immunoglobulin (IVIg), plasmapheresis, rituximab, eculizumab, cyclosporine, stem cell transplantation, and thymectomy. Multivariable logistic and Cox proportional hazards regression models were used to examine treatment associations with sex, adjusted for time from onset to diagnosis, age at diagnosis, presence of thymoma, and antibody status. A total of 179 people with gMG were included (41.9% female). Odds of starting treatment were not statistically associated with sex after adjustment for confounders and correction for multiple testing. Results of the secondary analysis using time to treatment initiation as the outcome were similar. We found no sex differences in odds of starting treatment or time to treatment initiation that might explain previously observed sex-based differences in QoL. Future work should capture physician and patient treatment preferences that may influence disease management.