Terms Of Adverse Events Research Articles

Description and Validation of a Novel AI Tool, LabelComp, for the Identification of Adverse Event Changes in FDA Labeling.

The accurate identification and timely updating of adverse reactions in drug labeling are crucial for patient safety and effective drug use. Postmarketing surveillance plays a pivotal role in identifying previously undetected adverse events (AEs) that emerge when a drug is used in broader and more diverse patient populations. However, traditional methods of updating drug labeling with new AE information have been manual, time consuming, and error prone. This paper introduces the LabelComp tool, an innovative artificial intelligence (AI) tool designed to enhance the efficiency and accuracy of postmarketing drug safety surveillance. Utilizing a combination of text analytics and a trained Bidirectional Encoder Representations from Transformers (BERT) model, the LabelComp tool automatically identifies changes in AE terms from updated drug labeling documents. Our objective was to create and validate an AI tool with high accuracy that could enable researchers and FDA reviewers to efficiently identify safety-related drug labeling changes. Our validation study of 87 drug labeling PDF pairs demonstrates the tool's high accuracy, with F1 scores of overall performance ranging from 0.795 to 0.936 across different evaluation tiers and a recall of at least 0.997 with only one missed AE out of 483 total AEs detected, indicating the tool's efficacy in identifying new AEs. The LabelComp tool can support drug safety surveillance and inform regulatory decision-making. The publication of this tool also aims to encourage further community-driven enhancements, aligning with broader interests in applying AI to advance regulatory science and public health.

A framework for assessment of adverse events occurring in psychedelic-assisted therapies.

Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed. A multidisciplinary working group of experts involved in PAT pooled formally and informally documented AEs observed through research experience and published literature. This information was integrated with (a) current standards and practices for AE reporting in pharmacotherapy and psychotherapy trials and (b) published findings documenting post-acute dosing impacts of psychedelics on subjective states, meaning, and psychosocial health variables, to produce a set of AE constructs important to evaluate in PAT as well as recommended methods and time frames for their assessment and monitoring. Correspondence between identified potential AEs and current standards for AE assessment was examined, including the extent of coverage of identified AE constructs by 25 existing measures used in relevant research. Fifty-four potential AE terms warranting systematized assessment in PAT were identified, defined, and categorized. Existing measures demonstrated substantial gaps in their coverage of identified AE constructs. Recommendations were developed for how to assess PAT AEs (including patient, clinician, and informant reports), and when to assess over preparation, dosing session, integration, and follow-up. Application of this framework is demonstrated in a preliminary assessment protocol (available in the supplement). This assessment framework addresses the need to capture post-acute dosing AEs in PAT, accounting for its pharmacotherapy and psychotherapy components, as well as documented impacts of psychedelics on worldviews and spirituality.

Long term patient outcomes and adverse events for acellular dermal matrix based breast reconstruction: A retrospective, observational study

Long term patient outcomes and adverse events for acellular dermal matrix based breast reconstruction: A retrospective, observational study

Risk of cardiovascular toxicity with combination of immune-checkpoint inhibitors and angiogenesis inhibitors: a meta-analysis.

Combinations of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AIs) have been investigated for the treatment of several tumor types. Both ICIs and AIs may lead to cardiovascular adverse events, and their combination may potentially increase the risk for cardiovascular toxicity. In the present meta-analysis, we aim to assess the cardiovascular toxicity of ICIs plus AIs vs. AIs alone. Secondary objectives are non-cardiovascular adverse events and efficacy. Systematic review was performed according to PRISMA statement. Phase II and III randomized clinical trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception to June 2022. The pooled risks for overall response rate (ORR), 1-year progression-free survival (PFS), adverse events (AEs), immune-related AEs, (irAEs), hypertension, and vascular events defined as stroke, myocardial infarction and pulmonary embolisms, were calculated. In terms of cardiovascular toxicity, we found higher risk for severe hypertension among patients treated with ICIs plus AIs as compared with those receiving AIs (OR 1.24, 95% CI: 1.01-1.53), but no significant difference was found for any-grade hypertension, and for vascular events. There was also no difference in terms of overall AEs, whereas the incidence of irAEs was increased in the ICIs plus AIs arm, as expected. In terms of efficacy, ICIs plus AIs achieved better ORR (OR 2.25, 95% CI: 1.70-2.97) and PFS (HR 0.49, 95% CI: 0.39-0.63) as compared to AIs alone. The addition of ICIs to AIs significantly increased the risk of high-grade hypertension, but not that of acute vascular events.

Assessment of safety profile of secukinumab in real-world scenario using United States food and drug administration adverse event reporting system database

Secukinumab is an anti-IL-17 monoclonal antibody approved for treating psoriasis and various arthritides. A comprehensive evaluation of its safety, especially in a real-world setting, is necessary. This study aimed to describe the adverse events (AE) associated with secukinumab use using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. FAERS data files containing AE reports from 2015 to 2021 were downloaded for data mining. Primary or secondary suspect medications indicated for psoriasis were identified and analyzed. Medical dictionary for regulatory activities (MedDRA version 24.1) was used to analyze the AE terms. To detect potential safety signals of AE from secukinumab use, disproportionality analysis was used. A total of 365,590 adverse event reports were identified; of these, 44,761 reports involved the use of secukinumab. Safety signals were identified for ocular infections and gastrointestinal adverse events at the standardised MedDRA query level. Safety signals for oral candidiasis, oral herpes, conjunctivitis, eye infections, and ulcerative colitis were identified at the preferred term level. The findings of our study are consistent with those of earlier studies, such as the increased risk of infections and inflammatory bowel disease. However, our study also identified additional safety signals that need to be further evaluated.

Adverse event reporting of four anti-Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: a real-world study based on the FDA adverse event reporting system.

Background: Anti-Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have shown significant efficacy in preventing migraine. However, there have been limited reports of adverse events (AEs) after marketing, particularly for eptinezumab launched in 2020. The study aimed to mine and analyze the AE signals with four anti-CGRP mAbs from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insights into the safety profile of these medications post-marketing. Methods: All AE reports on the four anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) were retrieved from the FAERS database from the first quarter (Q1) of 2018 to Q1 of 2023. Disproportionality analysis was measured by reporting odd ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential AE signals. Comparisons were made between the four drugs in terms of AEs. Results: A total of 38,515 reports of erenumab, 19,485 reports of galcanezumab, 5,332 reports of fremanezumab, and 2,460 reports of eptinezumab were obtained, mostly reported in the second to third year after launch in the market. The common AEs to erenumab included constipation (17.93%), injection site pain (14.08%), and alopecia (7.23%). The AEs that occurred more frequently with galcanezumab included injection site pain (24.37%), injection site erythema (5.35%), and injection site haemorrhage (4.97%). Common AEs related to fremanezumab were injection site pain (13.10%), injection site erythema (7.02%), and injection site pruritus (5.47%). Fatigue (13.54%), throat irritation (9.02%), and pruritus (8.20%) were the most common AEs with eptinezumab. In addition, there are new AEs that were not listed in the drug instructions but occurred concurrently with multiple drugs, such as Raynaud's phenomenon, weight increase, menstrual disorders, throat tightness, and paraesthesia oral. Conclusion: Common AE signals of the four anti-CGRP mAbs and new AE signals were found to provide a reference for clinical drug selection in clinical practice.

Efficacy and Safety of Sirolimus-Eluting Stent With Biodegradable Polymer Ultimaster™ in Unselected Korean Population: A Multicenter, Prospective, Observational Study From Korean Multicenter Ultimaster Registry.

Ultimaster™, a third-generation sirolimus-eluting stent using biodegradable polymer, has been introduced to overcome long term adverse vascular events, such as restenosis or stent thrombosis. In the present study, we aimed to evaluate the 12-month clinical outcomes of Ultimaster™ stents in Korean patients with coronary artery disease. This study is a multicenter, prospective, observational registry across 12 hospitals. To reflect real-world clinical evidence, non-selective subtypes of patients and lesions were included in this study. The study end point was target lesion failure (TLF) (the composite of cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]) at 12-month clinical follow up. A total of 576 patients were enrolled between November 2016 and May 2021. Most of the patients were male (76.5%), with a mean age of 66.0±11.2 years. Among the included patients, 40.1% had diabetes mellitus (DM) and 67.9% had acute coronary syndrome (ACS). At 12 months, the incidence of TLF was 4.1%. The incidence of cardiac death was 1.5%, MI was 1.0%, TLR was 2.7%, and stent thrombosis was 0.6%. In subgroup analysis based on the presence of ACS, DM, hypertension, dyslipidemia, or bifurcation, there were no major differences in the incidence of the primary endpoint. The present registry shows that Ultimaster™ stent is safe and effective for routine real-world clinical practice in non-selective Korean patients, having a low rate of adverse events at least up to 12 months.

Efficacy of Frontline Treatment with Initial Low-Dose Tyrosine-Kinase Inhibitors in Elderly Patients with Chronic Myeloid Leukemia: A “Campus CML” Study

Introduction Three TKIs, imatinib (IM), dasatinib (DAS) and nilotinib (NIL), are approved for frontline therapy in Italy. Choice of frontline TKI is based mainly on evaluation of patient's characteristics and clinical expectations. To avoid long term adverse events or potential drug interactions, elderly patients may start CML treatment with a frontline reduced dose of TKI (RD-TKI). Aim To analyse outcome of CP-CML patients aged over 65 years in a large and unselected cohort treated with RD-TKI. Methods We retrospectively evaluated 747 patients from 1/2012 to 12/2019 at 36 Hematology Centres participating at the “Campus CML” project. Results Clinical features for the whole cohort according to frontline TKI initial dose are reported in Table 1. Among all patients, 605 (81%) were treated with standard dose (SD) while the remaining 142 (19%) with reduced dose (RD). As to frontline TKI, 579 patients (77%) received IM and 158 (23%) a 2G-TKI (DAS n=78, 49%; NIL n=80, 51%). Of the 142 RD-TKI, 122 (85.9%) started with IM, 14 (9.9%) with DAS and 6 (4.2%) with NIL. Median RD was 100 mg for IM (range 100-300), 20 mg for DAS (range 20-50) and 250 mg for NIL (range 150-300). RD-TKI was mainly reported in IM treated patients (p=0.018), in elderly (p<0.001) and in patients with comorbidities, in particular diabetes (p=0.005) and ischemic heart disease (p=0.039). Number of concomitant drugs was also significantly associated with RD-TKI (p<0.001) probably to avoid drug interactions and subsequent toxicity. In detail, among RD-TKI, 41.1% of patients was treated with more than five concomitant drugs. Sokal score did not impact on TKI starting dose. No differences emerged between SD-TKI and RD-TKI in terms of haematological or extra-haematological toxicity. TKI frontline dose was not associated with difference in resistance, nor primary neither secondary resistance. Progression to blastic phase was reported in 1.2% of the whole population, none of which in RD-TKI. At 12 months no differences were noted in terms of achievement of major molecular response (MMR), obtained in 22.4% of SD-TKI treated patients and in 19% of RD-TKI treated patients. RD-TKI had inferior probability of deep molecular response (DMR) achievement (p=0.003), reported in 12.6% of patients. No differences were reported in 12-months cumulative rate of permanent discontinuation for any cause and for primary resistance between SD-TKI and RD-TKI as reported in Figure 1. Conclusions RD-TKI was a frontline treatment strategy used mainly in frail elderly patients, with more comorbidities and concomitant therapies. RD-TKI did not impact on primary resistance leading to TKI switch. While no differences were reported in the rate of MMR, the rate of 12-months DMR achievement was inferior in RD-TKI, but this result need to be confirmed with longer follow-up.

The added prognostic value of stress induced hyperglycemia to the GRACE risk score for the prediction of 1-year major adverse cardiovascular events in patients with ST-elevation myocardial infarction

Abstract Background There is growing evidence suggesting that Stress Induced Hyperglycemia (SIH) is a risk factor of poor prognosis in acute coronary syndrome (ACS)[1–3]. However, this parameter is not included in risk prediction scores, applied in clinical practice. Ιmportantly, there is no universally accepted definition for SIH especially in the setting of ACS. Across the existing evidence base, SIH is defined either based on admission blood glucose (ABG) levels or by calculating the glycemic gap and the stress hyperglycemia ratio (SHR)[4]. Purpose Considering the variability in SIH definitions and the need for further investigation on the long-term prognostic impact of SIH, we present herein original data concerning the prognostic role of SIH for long-term risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients presenting with ST-elevation myocardial infarction (STEMI) on top of a traditional prediction risk score such as the GRACE 2.0 risk score. Methods Our data were derived from a post-hoc analysis of a prospective study (NCT04580173). Every trial procedure was conducted according to the principles set by the declaration of Helsinki. Each participant provided written informed consent before being enrolled in the study. Our analysis included 309 consecutive STEMI patients who were diagnosed with SIH if ABG was > 140 mg/dl and a fasting period of at least 8 hours was confirmed. Each participant was followed-up for a median 1-year period. Baseline characteristics of the included patients are presented in Table 1. The records of all enrolled patients were retrospectively analyzed to calculate the GRACE 2.0 risk score for each patient. Results Cox regression analysis adjusted for age, gender, body mass index (BMI), hypertension, smoking, and SIH was performed but did not identify GRACE risk score>140 as an independent predictor of MACCE (aHR=1.408, 95% CI:0.764-2.594 p=0.273, Figure 1). On the other hand, a similar model adjusted for the same covariates identified the combination of GRACE risk score>140 and SIH as a significant predictor of MACCE occurrence (aHR=2.149, 95% CI:1.224-3.771, p=0.008). Conclusions Our results suggest that SIH combined with the GRACE 2.0 risk score was associated with improved prediction of the risk for 1-year MACCE in STEMI patients as compared to the GRACE 2.0 risk score alone. In this study, SIH was diagnosed based on the levels of admission blood glucose (after 8-hours of fasting) and not based on the SHR. Despite the heterogeneity in SIH definitions, stress hyperglycemia in the setting of STEMI might be an underrated yet robust prognostic marker not only for short term but also for long term adverse clinical events, especially when integrated in existing clinical risk scores.Survival curveBaseline characteristics

Early stellate ganglion block for improvement of postoperative cerebral blood flow velocity after aneurysmal subarachnoid hemorrhage: results of a pilot randomized controlled trial.

Stellate ganglion block (SGB) is a commonly used sympathetic nerve block technique that may have benefits for patients with aneurysmal subarachnoid hemorrhage (aSAH) in the early stage. Cerebral vasospasm (CVS), one of the most common complications of aSAH, is accompanied by an abnormal increase in cerebral blood flow velocity (CBFV) and neurological dysfunction. In this pilot study the authors sought to determine the feasibility of early SGB for CVS in aSAH patients by observing the incidence of symptomatic CVS. Prior to receiving surgical treatment, patients with aSAH were randomly assigned to the SGB group or the non-SGB group. The primary outcome was the incidence of symptomatic CVS within 14 ± 2 days after the onset of aSAH. As a higher CBFV is often associated with CVS and a poor prognosis, the mean CBFV of the middle cerebral artery was observed immediately after surgery and on postoperative days 1, 2, 3, 5, and 7. Other secondary outcomes included transcranial Doppler (TCD)/CTA-type CVS, delayed cerebral ischemia during hospitalization, new cerebral infarction within 3 months, adverse events (AEs), and clinical prognosis. Symptomatic CVS occurred in 40% of patients in the non-SGB group and in 20% in the SGB group (RR 0.50, 95% CI 0.22-1.16). Continuous TCD sonography revealed that the postoperative mean CBFV was lower in the SGB group than in the non-SGB group (F = 3.608, p = 0.02). In addition, the percentages of patients with CVS evaluated by TCD (TCD-CVS) and total new infarctions within 3 months were also significantly lower than those in patients with CVS (TCD-CVS 36.7% vs 70%, RR 0.52, 95% CI 0.31-0.89, and total new infarctions 26.7% vs 53.3%, RR 0.50, 95% CI 0.25-0.99). In terms of AEs and mortality, there were no significant differences between the two groups. This pilot study demonstrated for the first time, to the authors' knowledge, that early SGB is feasible and has the potential to reduce the risk of CVS and improve the prognosis of aSAH. This method may be a new treatment for patients with aSAH that may have more advantages than traditional therapeutic drugs and is worth further study. Clinical trial registration no.: NCT04691271 (ClinicalTrials.gov).

64 Long term adverse events in adolescent visiting the emergency department with cardiovascular adverse reactions after COVID-19 vaccination

64 Long term adverse events in adolescent visiting the emergency department with cardiovascular adverse reactions after COVID-19 vaccination

Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials.

Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have been published showing that zolbetuximab is associated with improved prognosis in patients with advanced gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. This promises great change to the current treatment landscape. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma. The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 2023). All randomized trials comparing zolbetuximab plus chemotherapy versus first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes and measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). This systematic review and meta-analysis included three randomized controlled studies involving 1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high expression, while there was significant benefit in patients with lower expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting were more common. This systematic review and meta-analysis revealed that the effect of zolbetuximab plus chemotherapy was superior to that of chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line treatment for these patients. Zolbetuximab plus chemotherapy was associated with higher risk of grade 3 and higher AEs, but was generally manageable. https://www.crd.york.ac.uk/prospero, identifier (CRD42023437126).

Comparative Efficacy and Safety of Five Anti-Calcitonin Gene-Related Peptide Agents for Migraine Prevention: A Network Meta-Analysis.

Anti-Calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies (mAbs) for migraine prevention. In this network meta-analysis (NMA), the efficacy and safety of migraine treatments including different doses of atogepant and CGRP mAbs were evaluated to provide a reference for future clinical trials. A search using PubMed, Embase and Cochrane Library identified all randomized controlled trials (RCTs) published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias. In this study, 24 articles were considered for analysis. Regarding effectiveness, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225mg in change from baseline of migraine days (SMD=-0.49,95%CI[-0.62, -0.37]) and 50% response rate (RR=2.98,95%CI[2.16,4.10]), while the optimal choice for reducing acute medication days was monthly erenumab 140mg(SMD=-0.68,95%CI[-0.79, -0.58]). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240mg and quarterly fremanezumab 675mg. There was no significant difference in discontinuation due to AEs between interventions and placebo. All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225mg, monthly erenumab 140mg, and daily atogepant 60mg were effective interventions with fewer side effects.

A Phase II, Randomized, Double Blind, Placebo Controlled Study of the Safety and Efficacy of a Caffeine-Based Antifibrosis Cream in Patients with Breast Cancer Undergoing Radiation Therapy

Radiation induced fibrosis (RIF) is a common long term adverse event in patients undergoing post-mastectomy radiation therapy (PMRT) which can cause capsular contracture, implant loss, and reconstruction complications in women with implant-based breast reconstruction. At a molecular level, adenosine is a driver of RIF. Preclinical data have shown that pharmacologic blockade of the adenosine A2A Receptor (A2AR) in mice as well as an A2AR knockout mouse model prevented skin fibrosis associated with radiation injury. Caffeine is an A2AR antagonist which has been shown to block the development of hepatic fibrosis in liver disease patients. We present a phase II placebo controlled clinical trial to evaluate whether a caffeine-based cream can prevent RIF and thus reduce the rates of reconstructive complications in patients with tissue expander-based reconstruction requiring PMRT. Women ≥ 18 years old with breast carcinoma stage 0-III status post mastectomy with tissue expander-based reconstruction who require PMRT to the chest wall +/- the regional nodes are being enrolled. The target accrual is 60 patients. Boost field to the chest wall, scar and/or nodal region is allowed. Patients with inflammatory breast cancer or those requiring skin bolus are excluded. Prior to starting radiation, patients will be randomized to placebo vs. caffeine cream and they will be instructed to apply the cream twice a day starting on the first day of radiation treatment and continuing daily for the duration of radiation until the removal of tissue expanders. The primary study endpoint is reconstructive complications requiring rehospitalization or reoperation by 2 years post radiation including reconstructive failure with or without reconstruction. A safety endpoint of grade ≥ 2 acute radiation dermatitis will also serve as a co-primary endpoint. Secondary endpoints are wound infection/cellulitis, hematoma, seroma, threatened exposure, wound dehiscence, implant leakage, rupture, and or deflation, and capsular contracture that do not meet criteria for the primary endpoint. Clinician rated cosmesis, local recurrence, regional recurrence, distant metastasis and survival up to 4 years are additional secondary endpoints. Exploratory endpoint includes the use of shear wave elastography (SWE) as a potential tool to quantitatively measure post irradiation fibrosis. Correlative aims include assessing epidermal thickness and fat layer thickness from tissue obtained at time of implant exchange for association with the development of fibrosis. The primary efficacy endpoint will be estimated using Kaplan Meier methods from date of randomization. Treatment comparisons will be based on a 2-sided log rank chi-square test and the hazard ratio will be estimated with 95% confidence intervals. The study started accruing in 12/2019 and is estimated to end by 04/2024. As of January 2023, 67% (40/60 patients) of the planned patients have been enrolled. To be determined. To be determined.

Quality of Life Results of Addition of Androgen Deprivation Therapy and Pelvic Lymph Node Treatment to Prostate Bed Salvage Radiotherapy: NRG Oncology/RTOG 0534 SPPORT

Report the quality of life (QOL) analysis of the SPPORT trial of men with a detectable prostate specific antigen (PSA) after prostatectomy for prostate cancer randomized to (Arm 1) salvage prostate bed radiotherapy (PBRT), (Arm 2) 4-6 months of short-term androgen deprivation therapy (STADT) + PBRT, and (Arm 3) pelvic lymph node radiotherapy (PLNRT) + STADT + PBRT. Primary analysis established a benefit of adding PLNRT and STADT to PBRT. There was higher short term but no statistically significant difference in long term adverse events with the exception of blood or bone marrow events. QOL endpoints were assessed at baseline, 6 weeks after RT start, 1 and 5 years, including Expanded Prostate Cancer Index Composite (EPIC) (bowel, urinary, sexual, and hormonal domains), Hopkins Symptom Checklist (HSCL-25) (depressive symptoms), and the EuroQol (EQ-5D) (health state weights used in quality adjusted life years (QALYs). In addition to statistical significance, differences in scores were assessed using 0.5 standard deviation (SD) as the criterion for clinical importance. Difference among arms was assessed using pairwise t-tests, Fisher's exact test, and mixed effects regression modeling. To control for multiplicity, the p-value required for statistical significance is p<0.025. Six hundred forty-four patients consented to QOL, about 210 on each arm. Baseline characteristics were not significantly different among arms: 81% were white and 54% <65 years. For EPIC, bowel domain scores decreased at 6 weeks post-RT then increased by years 1 and 5, although not to baseline levels. One clinically significant difference in bowel scores was Arm 3 vs. Arm 1 at 6 weeks. For the urinary domain, scores decreased at 6 weeks post-RT and remained below baseline at 1 and 5 years, but there were no significant differences among arms. For the sexual domain, there were statistically significant differences between arms at 6 weeks and 1 year with patients receiving STADT exhibiting poorer sexual QOL scores. By year 5 the differences were no longer significant. A similar pattern was seen for the hormonal domain. For HSCL-25, differences at 6 weeks were statistically but not clinically significant, and there were no significant differences at the later time points. Comparisons of QALYs for overall survival over an 8-year horizon showed no significant group differences, with a mean of about 7.8 in each arm. Regarding freedom from progression, QALY means were 5.7, 6.5, and 7.4 years for Arms 1, 2, and 3, respectively, with a significant difference between Arms 3 and 1 (p = <.001) favoring the more intensive treatment. While QOL generally declined among all arms at 6 weeks post RT, there were no clinically significant differences in QOL among arms at 5 years. QALYs for freedom from progression favored STADT + PLNRT + PBRT for salvage treatment of prostate cancer.

Maternal and Neonatal Outcomes of Sub-clinical Hypothyroidism Treated With Levothyroxine in Pregnancy: A Retrospective Cohort Study.

The effect of sub-clinical hypothyroidism (SCH) in pregnancy has been controversial. Furthermore, the impact of levothyroxine replacement on improving outcomes in pregnant women with SCH is unknown. This study aimed to assess the maternal and neonatal outcomes of pregnant women with SCH who were treated with levothyroxine replacement. This retrospective chart review was conducted at a tertiary hospital in Iran between 2020 and 2022. All pregnant women who had given birth during the study period were recruited. Those who did not have thyroid function test results within 10-12 weeks, as well as those with SCH who did not have levothyroxine replacement, were excluded. The subjects were divided into two groups based on the 2017 American Thyroid Association (ATA) criteria: non-SCH (TSH values 0.27-2.5 mIU/L) and SCH (TSH values more than 4.0 mIU/L). The demographic, obstetric, maternal, and neonatal outcomes of both groups were compared. The Chi-square test was used to compare the categorical variables. Binary logistic regression was used to assess differences in categorical variables. With a frequency of 10.5%, 935 women out of 8888 were diagnosed with SCH. In terms of age, educational level, living residency, medical insurance, access to prenatal care, and smoking status, there were no differences between the two groups. In terms of gestational age, parity, onset of labor, history of infertility, hypertension, cardiovascular disease, anemia, and overt diabetes, there were no differences between the two groups; however, gestational diabetes was more common in those with SCH. Compared with the non-SCH group, the prevalence and risks of gestational diabetes [19.8 vs. 14.2, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.72-3.95] were significantly higher in the SCH group after controlling for confounding factors. There were no differences in neonatal outcomes between the two groups. Except for gestational diabetes, we found no significant adverse events in terms of maternal and neonatal outcomes among women with SCH who were treated with levothyroxine.

The efficacy and safety of immune checkpoint inhibitors for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy: A systematic review and network meta-analysis.

Non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-mutated who progressed on EGFR tyrosine-kinase inhibitor (EGFR-TKI) therapy have limited therapeutic options. There is still no consensus on the role of immune checkpoint inhibitors (ICIs) in NSCLC with EGFR mutations. We did a network meta-analysis (NMA) with a systematic literature search on PubMed, Embase, Web of Science, and The Cochrane Library. We included all phase II and III randomized controlled trials (RCTs), non-randomized controlled trials (Non-RCTs), and retrospective studies. Progression-free survival (PFS) and overall survival (OS) were assessed through hazard ratios (HR). Objective response rate (ORR) and adverse events (AEs) were assessed through odds ratio (OR) and relative risk (RR), respectively. R software was used to compare the outcomes of different treatments by Bayesian NMA. We identified 1835 published results and 17 studies were included ultimately. A total of 2085 patients were included and accepted the following six treatments: ICIs plus chemotherapy (ICIs+Chemo), chemotherapy (Chemo), ICIs monotherapy (ICIs), ICIs plus chemotherapy and antiangiogenic therapy (ICIs+Chemo+Antiangio), antiangiogenic therapy plus chemotherapy (Antiangio+Chemo), ICIs plus antiangiogenic therapy (ICIs+Antiangio). ICIs+Chemo+Antiangio was associated with longer PFS and OS, as well as higher ORR (surface under the cumulative ranking curve [SUCRA], 96%, 90%, 91%). ICIs conferred the safety profile in terms of any-grade AEs, grade greater than or equal to 3 AEs and any grade leading to treatment discontinuation occurred AEs (SUCRA, 99%, 68%, 94%). ICIs+Chemo+Antiangio brings the greatest survival benefit in NSCLC patients with EGFR mutations who progressed on EGFR-TKI therapy, even for whom with baseline brain metastases. Compared with chemotherapy, ICIs has a low incidence of AEs and a benefit in OS.

Comparison of first-line treatments for recurrent or metastatic nasopharyngeal carcinoma based on phase 3 randomized clinical trials.

e18012 Background: Guidelines recommend platinum-based chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients. There are a variety of available combination treatment options, however, there is lack of research evaluating their advantages and disadvantages. Therefore, this study aims to compare the efficacy and adverse events (AEs) of the first-line treatment for R/M NPC. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for phase 3 randomized clinical trials (RCTs) in which two first-line treatments for R/M NPC were compared. Among the included trials, progression-free survival (PFS) and overall survival (OS) were calculated using the hazard ratio (HR) and 95% Bayesian confidence interval (95% CrI), while the odds ratio (OR) and 95% CrI were used to evaluate the incidence of severe AEs. The cumulative ranking plot and surface under the cumulative ranking curve (SUCRA) were used to evaluate the rank probability of each regimen. Results: Three trials involving 4 total regimens were included. In terms of PFS, toripalimab plus gemcitabine plus cisplatin (GP) (HR: 0.28; 95% CrI: 0.081-0.98) and camrelizumab plus GP (HR: 0.28; 95% CrI: 0.079-0.96) were significantly superior to fluorouracil plus platinum (PF). In the rank analysis, camrelizumab plus GP was most likely to be the best regimen (SUCRA = 0.81), followed by toripalimab plus GP (SUCRA = 0.80). There was no significant difference among these treatments in terms of OS or AEs. Conclusions: This is the first network meta-analysis comparing the pros and cons of first-line regimens for R/M NPC based on phase 3 randomized clinical trials. Our research showed that toripalimab/camrelizumab plus GP was found to be the most effective treatment regimens for the first-line treatment for R/M NPC in terms of PFS.

P307 "REAL WORLD" EVALUATION OF LONG–TERM OUTCOMES RELATED TO FIRST AND SECOND GENERATION BIORESORBABLE AVASCULAR SCAFFOLDS

Abstract Introduction The studies currently available in the literature support worse outcomes in first generation bioresorbable scaffold (Absorb; Abbott USA) compared to second generation devices (Magmaris; Biotronik CHF); the proposed retrospective study aims to analyze and compare long–term adverse events in the two groups and to estimate any predictors. Methods and Results 236 consecutive cases selected between 2012 and 2018 from the hemodynamic registers of the Aosta valley health authority (VdA) and subjected to an average follow–up of 72.0 months, the composite endopint (Mortality, Target Lesion Revascularization, Target Vessel Myocardial Infarction, Stent Thrombosis) involved 38 patients (16.1%) in the Absorb group and 7 subjects (9.1%) treated with the Magmaris stent (p=0.058), with a lower number of ST and TVMI in the second group. The total mortality rate was very low in both populations, and it appears to be linked mainly to non–cardiac causes. The duration of DAPT seems to confirm a protective role against adverse events (HR 0.79; p = 0.14). Conclusions The results obtained, with the limitations related to the low sample size and the nature of the study, confirm the lower long–term complication rate of new generation stents compared to first generation stents. Prolonging DAPT appears to be a reasonable choice in subjects treated with resorbable stents.

Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis (P7-3.013)

Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis (P7-3.013)