Post-marketing Data Research Articles

Safety Profile of Molnupiravir in the Treatment of COVID-19: A Descriptive Study Based on FAERS Data

Concerns have been raised about the actual benefit and safety of molnupiravir, a new antiviral treatment for coronavirus disease 2019 (COVID-19). In order to provide additional evidence to support its use, we aimed to evaluate the real safety profile based on post-marketing pharmacovigilance data. Molnupiravir safety data were captured from the FDA Adverse Event Reporting System (FAERS). We performed a descriptive analysis of the baseline demographic characteristics of patients who experienced at least one adverse drug reaction (ADRs) related to molnupiravir, and then evaluated those most frequently reported. As of 31 March 2022, 612 reports of ADRs related to molnupiravir were submitted to the FDA, 301 (49.18%) were related to females and 281 (45.92%) to males. Most reports (524; 85.62%) were submitted by healthcare professionals and 345 (56.37%) concerned serious outcomes. The most common reported ADRs were diarrhoea (57; 4.51%), rash (36; 2.85), nausea (29; 2.30%), and COVID-19 pneumonia (22; 1.74%). The most frequent adverse reactions reported with molnupiravir in the U.S. post-marketing experience are consistent with the safety evaluation of the antiviral medicine. Even if no evident safety concerns emerged, an unexpectedly high rate of serious adverse reactions together with a few cases of potential new adverse reactions occurred.

1422. A Multi-Center Evaluation of Omadacycline for Multi-Drug Resistant Infections

Abstract Background Multi-drug resistant (MDR) pathogens are a continuously evolving threat for which there are limited effective treatment modalities. Omadacycline (OMC) is a novel oral and intravenously administered aminomethylcycline with potent in-vitro activity against MDR gram-negative and gram-positive pathogens. Post-marketing data investigating its potential place in the antibiotic armamentarium is limited. This study aimed at describing the clinical success and tolerability of patients receiving OMC for various infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to March 30, 2022. We included all patients ≥ 18 years of age that received OMC for any infection not related to Mycobacterium spp. for ≥72 hours. The primary outcome was clinical success at 30 days, defined as survival, the absence of persistence or re-emergence of infection during or after therapy, and the absence of escalation or alteration of OMC. Incidence of adverse effects while on OMC and reasons for OMC utilization were also analyzed. Results This analysis included 19 patients from 10 distinct academic centers. The median age was 50 years (IQR, 37-63), 58% were male, 63% were Caucasian, and the median APACHE II, Charlson and SOFA scores were 10 (IQR 5-12.5), 4 (IQR 2-6.3), and 1 (IQR 0 – 2.25), respectively. Most patients had a bone and joint (8/19, 42.1%) or intra-abdominal infections (4/19, 21.1%), all with positive cultures. Eight patients (44.1%) had a polymicrobial infection and 4 (22.2%) had bacteremia. The most common pathogens encountered were Carbapenem-resistant A. baumannii (5/19, 27.8%), E. coli (5/19, 27.8%), Vancomycin-resistant Enterococcus spp. (4/19, 22.2%), and K. pneumoniae (3/19, 16.7%). Clinical success was observed in 14 patients (74%) and 7 (36.8%) received combination therapy. Adverse drug reactions were reported in 3 patients (15.8%) and of those patients, none discontinued therapy. Reasons for prescribing OMC were mostly attributed to oral availability (12/14, 85.7%) and resistance to other agents (7/14, 50%). Conclusion OMC demonstrated clinical effectiveness and safety against a large number of MDR pathogens. More robust, prospective, comparative studies are needed to confirm our preliminary findings. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

Can glucagon-like peptide-1 receptor agonists cause acute kidney injury? An analytical study based on post-marketing approval pharmacovigilance data.

FAERS data from January 2004 to December 2021 were mined using disproportionality analysis and Bayesian analysis to determine the correlation between different GLP-1RA and AKI, and the onset time, mortality, and hospitalization rate of different GLP-1RA were analyzed. We identified 2670 cases of AKI events associated with GLP-1RA, of which liraglutide was the most commonly reported (34.98%). The patients with AKI were mainly males (47.94%), and the age group was mainly 45-84 years old (73.15%). obese patients with weight more than 99kg (24.42%) were more likely to have AKI. According to different signal mining methods, reporting odds ratio (ROR) (1.50, 95% confidence interval =1.41-1.60) and Bayesian confidence Propagation neural network (0.57, 95% confidence interval =0.54), liraglutide was more strongly associated with AKI than other GLP-1RA. The median time to onset of AKI was 63 days [quartile range (IQR): 15-458.5 days]. In addition, the hospitalization rate and fatality rate of patients with GLP-1RA-related AKI were 45.28% and 4.23% respectively. Based on the data in the FAERS database, we analyzed the risk, onset time, and adverse reaction outcomes of GLP-1RA-induced AKI in detail. The results showed that liraglutide had the highest risk of AKI. From the early stage of treatment, we need to monitor patients' renal function regularly, especially for patients with high kidney risks such as obesity and age.

Safety of oral nemonoxacin: A systematic review of clinical trials and postmarketing surveillance.

Background: Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin malate, the first approved C-8-methoxy non-fluorinated quinolone, in clinical studies and via postmarketing safety surveillance. Methods: We electronically and manually searched and screened safety data (including premarketing and postmarketing data) of oral nemonoxacin from clinical registries. We standardized and summarized the reported adverse events according to the Medical Dictionary for Regulatory Activities System Organ Class and Preferred Terms. We summarized and reported the number and frequency (%) of the AEs and serious AEs in patients with community-acquired pneumonia and in specific patients. Results: Three Phase II/III comparator studies (n = 670, nemonoxacin), one Phase IV study (n = 461), two special population pharmacokinetic studies (n = 40), four observational studies (n = 1,852), and one 5-year postmarketing surveillance project (n = 257,420) were included in this study. The Phase II/III studies showed that the commonly reported drug-related AEs were similar for oral 500mg nemonoxacin and levofloxacin treatments, which mainly included increased alanine aminotransferase levels (4.4% vs. 2.5%), neutropenia (2.5% vs. 4.4%), nausea (2.5% vs. 1.6%), and leukopenia (2.3% vs. 3.2%). No drug-related deaths were reported. Postmarketing safety surveillance revealed that known adverse drug reaction characteristics were generally unchanged. Pharmacokinetic data suggested that dose adjustment was not necessary in elderly patients, which was confirmed by a Phase IV study in an elderly population, in patients with renal impairment with CLcr ≥50ml/min, and in those with mild-to-moderate hepatic impairment. Conclusion: Clinical trial data of approximately 1,450 patients and postmarketing data of >257,420 patients suggest that nemonoxacin is generally well tolerated and can be a suitable alternative to fluoroquinolones for patients with CAP.

Safety and Effectiveness of Etanercept Biosimilar SB4 for Rheumatic Diseases in South Korea: Real-World Post-marketing Surveillance Data.

SB4 is the first approved biosimilar of etanercept, a biologic tumor necrosis factor inhibitor, to treat various autoimmune diseases including axial spondylarthritis (axSpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and plaque psoriasis (PsO). This post-marketing surveillance (PMS) study of SB4 investigated safety and effectiveness in routine clinical practice and is part of the drug approval process in Korea. This prospective, multi-center, open-label, observational, phase IV PMS study was designed to enroll patients with axSpA, RA, PsA, and PsO in Korea from September 2015 to September 2019. Both etanercept-naïve patients or patients switched from reference etanercept were included. SB4 was administered weekly via subcutaneous injections using pre-filled syringes. Safety was assessed by the incidence of adverse events (AEs), adverse drug reactions (ADRs) and serious adverse events (SAE). Effectiveness was assessed by the change from baseline of investigator-rated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with ankylosing spondylitis (AS) and disease activity score-28 (DAS28) in patients with RA. Among 316 enrolled patients, 314 were included in the safety analysis (176 with AS and 138 with RA). The overall incidence of AEs, ADRs and serious AEs were 17.8, 9.9, and 1.3%, respectively. Most AEs were mild (66.7%) or moderate (31.1%) and not related to SB4 (58.9%). Most common AEs were injection site pruritus (1.9%) and injection site rash (1.3%). At week 24, mean disease activity scores significantly decreased compared to baseline in naïve patients with AS and RA (BASDAI 2.7 vs. 6.2, p < 0.0001; DAS28 3.8 vs. 5.7, p < 0.0001) and in switched patients with AS and RA (BASDAI 1.0 vs. 1.3, p = 0.0018; DAS28 2.4 vs. 2.9, p = 0.0893). This first real-world evidence of SB4 from a phase IV PMS study in Korea shows comparable effectiveness to historical SB4 real-world evidence without any new significant safety signals.

An observational study of adverse drug reactions to COVID-19 vaccines reported to the New Mexico poison center hotline

Introduction Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. Methods We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. Results 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. Conclusion This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.

A Comprehensive Review of Spinal Cord Stimulator Infections.

Spinal cord stimulator (SCS) is approved to treat various pain conditions and is commonly seen in the chronic pain patient population.Due to the nature of the device and its location, infections associated with SCS have a particularly high morbidity.According to post-market data and medical device reports, 87% of patients receiving SCS implants were given perioperative antibiotics as the implantable neurostimulator or receiver pocket serve as the most common sites of infection. The most common antibiotics for surgical prophylaxis given are first-generation cephalosporins (cefalexin, cefazolin) at the time of implantation.If deep infection is suspected, imaging in the form of CT scan should be obtained as physical exam is not always sufficient. For infections involving the epidural space, vertebra, or intervertebral discs, MRI is the preferred imaging modality. If meningitis is suspected, a lumbar puncture is recommended. Positive cultures can help guide antibiotic therapy.

Regulatory Measures to Improve the Safety of CAR-T-Cell Treatment

Introduction: Regulatory activities aim to facilitate the safe use of novel therapeutics such as genetically engineered chimeric antigen receptor (CAR)-T cells. Toxicities associated with CAR-T-cell therapies have led to modified safety management guidance in clinical trials and the implementation of post-marketing requirements. The aim of this study was to estimate the effect of individual risk-minimizing measures to evaluate the appropriateness of regulatory activities. Methods: We re-examined clinical trial data prior to and after the introduction of revised treatment guidelines; we analysed spontaneous adverse drug reaction (ADR) reports submitted to the EudraVigilance database in 2019/2020 regarding their completeness; and we performed a survey of treatment centres in Germany that have been qualified for the use of commercial CAR-T cells. Results: Lower combined incidences of severe cytokine release syndrome (CRS) as well as neurotoxicity occurred following CAR-T-cell treatment after a revision of management guidelines, suggesting earlier intervention compared to before (12.6% vs. 20.5%). Numerous post-marketing ADR reports lacked information important for case assessment. Full details on treatment indication, CRS onset, outcome, and grading were available for just 38.3% of CRS cases. Survey responses support the majority of regulatory requirements for centre qualification. Time investment was highest for training of healthcare professionals, which required an average of 6.5 staff members (range 2–20) and lasted more than 2 days per person in half of the facilities. The need to harmonize the regulatory requirements for the different CAR-T-cell therapeutics was emphasized. Conclusion: Defined regulatory measures can support the safe and effective use of new therapies and are indicated for structured recording of post-marketing data, and the evaluation of such measures appears to be necessary for the continuous improvement.

Analysis of Reported Adverse Events Related to Over-the-Scope Clips: A MAUDE Database Analysis

Background and AimsOver-the-scope clips (OTSCs) have been increasingly used in the management of bleeding, perforations, fistulae, and anastomotic leaks in the gastrointestinal tract. However, since their Food and Drug Administration (FDA) approval in 2010, data on the adverse events of OTSC systems have been lacking. The aim of our study was to report and analyze adverse events and device failures associated with OTSC systems using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. MethodsWe analyzed the FDA MAUDE database post-marketing surveillance data from January 2013 through May 2022 on the two OTSC systems available in the United States. ResultsForty medical device reporting claims were found from January 2013 through May 2022. Adverse events were classified as device-related problems and patient-related adverse events. Forty device-related problems were reported, along with 20 device-related adverse events. Most device-related problems were reported in the Padlock defect closure system (n = 23), followed by the Padlock pro clip system (n = 8) and Ovesco OTSC system (n = 9). The most common device-related problem was related to the failure of OTSC deployment (n = 13), followed by material protrusion or extrusion (n = 7). The most common patient adverse events were perforation (n = 4), esophageal laceration (n = 4), bleeding (n = 3), and luminal stenosis (n = 3). All 4 patients required surgical management of the perforation. No deaths related to the use of OTSCs were reported. ConclusionFailure of OTSC deployment and perforation were the most common device-related problem and patient-related adverse event, respectively. As the use of OTSC systems continues to increase, it is important for endoscopists to be mindful of both the common and rare adverse events associated with OTSC use.

MRNA COVID-19 vaccines are well tolerated and myopericarditis is a rare adverse event following immunisation.

mRNA vaccines are considered to be important tools for the management of the COVID-19 pandemic. Although mRNA COVID-19 vaccines are well tolerated in most recipients, post-marketing data have highlighted an association between myocarditis and mRNA vaccines. Post-vaccine myocarditis (PVM) is most commonly reported in male adolescents receiving the second dose of an mRNA vaccine. However, the incidence of PVM is low and the risk of myocarditis should be kept in perspective. Cases of PVM are mostly mild in severity, and may be managed using existing myocarditis guidelines. The pathology of PVM is under investigation, and current data suggest that cross reactivity or hypersensitivity reactions may be involved. Globally, mRNA vaccines are generally recommended for use in children/adolescents, and delaying the administration of the second dose may reduce the risk of PVM.

The evolution of pharmacovigilance ecosystems: Does Moore's law invite the use of Occam's razor?

Moore's law predicts the doubling of complexity of integrated circuits every 2 years; Kryder's corollary assumes a doubling of data storage every 13 months. With the increasing volume of legislation, pharmacovigilance systems today are inherently complex, and the emphasis has shifted from reactive (responding to emerging risks) to planned, active, risk-proportionate approaches operating throughout the life cycle of medicines. Exploration of the drivers for increasing complexity of pharmacovigilance systems, focusing on regulatory environment, data management and evaluation. Evaluation of postmarketing data plays an increasingly important role in pharmacovigilance. There is great interest on the part of all stakeholders in optimizing the use of these data. Innovative approaches, including pharmacogenetics and passive measures (sensors), will lead to increased complexity and volumes of data and inevitably to an increase in the volume of case reports. There is a multiplicity of regulations and guidelines on how to manage these data, with an inherent lack of harmonization. We summarize the current characterization of safety data types, sources and the classification of these data. Using this benchmark, we discuss the future requirements of an effective pharmacovigilance ecosystem, keeping the principle of parsimony in mind. In this complex, continuously and rapidly changing environment, there is a need for a return to simplicity and pragmatism. The application of Occam's razor could help to support the rapid provision of new, affordable medicines with a positive benefit to risk profile.

Depicting Risperidone Safety Profiles in Clinical Trials Across Different Diagnoses Using a Dopamine D2-Based Pharmacological Class Effect Query Defined by FAERS.

Current methods are not designed to relate the incidence of individual adverse events reported in clinical trials to the plurality of adverse events accumulated in spontaneous reporting databases during real-world use. We have previously reported on a pharmacological class-effect query of clinical trial data defined by a disproportionality analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) post-marketing data. The aim of the current analysis was to apply a dopamine D2-based pharmacological class-effect query to clinical trial safety data of an atypical antipsychotic tested across different patient populations. Patient-level adverse event data (n = 4400) from controlled clinical trials of the antipsychotic risperidone in schizophrenia, bipolar disorder, Alzheimer's disease psychosis, and autism were obtained through the Yale University Open Data Access (YODA) project. An Empirical Bayes Geometric Mean analysis was performed, and a three-fold threshold incidence level was applied to determine if a preferred term met criteria for being an antipsychotic class-related adverse event. In pooled data from seven trials of adult schizophrenia, class-specific adverse events were identified in 49% of patients treated with risperidone; in 49% of risperidone-treated patients in two trials in adolescent schizophrenia; in 65% of risperidone-treated patients in four trials in adult bipolar disorder; in 50% of risperidone-treated patients in two trials in adolescent schizophrenia; in 36% of risperidone-treated patients in one trial in Alzheimer's disease; and in 94% of risperidone-treated patients in one trial in autism. The cumulative curves of class-specific adverse events in risperidone clinical trials of schizophrenia were similar to those first reported for other atypical antipsychotic drugs. However, the class-specific adverse event curves were notably lower for Alzheimer's disease and higher for autism, suggesting that the diagnostic indication may have an important effect on the cumulative class-specific side-effect burden.

Abstract 240: High First Shock Success With Reduction In Refractory Ventricular Fibrillation In A Real-world Public Access Defibrillator Registry Of Out-of-hospital Cardiac Arrests

Introduction: Refractory VF, which is defined as fibrillation that persists after three or more shocks, has been reported to occur in 20% of VF presenting cardiac arrest patients. This analysis was conducted to assess the frequency of shock resistant VF, during OHCA treated with a public access defibrillator (PAD). Methods: Heartsine Samaritan PAD post-market data collected between October 2012 to January 2021 were analyzed; electrocardiography (ECG) is recorded by the PAD and is assessed for shockability immediately after detecting patient impedance and then following each 2-minute period of CPR. Shock success (SS) was determined for each shock. SS was defined as one in which the initial shockable arrhythmia was terminated for at least five seconds. A consecutive shock was defined as a shock delivered after the first analysis mode following a previous shock. Results: Data was analyzed for 1082 patients who received at least one shock during OHCA. First shock success (FSS) was 88.2% (862/977 assessable shocks). At least three consecutive shocks were delivered in 207/1082 (19.1%) patients. Three patients (3/207, 1.4%) had two unsuccessful shocks followed by termination of VF on the third shock. A further thirteen (13/204, 6.4%) patients had VF which was resistant to defibrillation (i.e., three or more consecutive failed shocks with no observed successful shock). In the remaining 191 patients at least one of the three consecutive shocks was successful, or shock success could not be determined. Conclusion: The prevalence of shock resistant VF for OHCA treated with a PAD is much lower (6.4%) than published data. This low prevalence is in part due to the high FSS observed resulting in reduction in the number of possible shock resistant cases.

Abstract 253: Decline In Initial Shockable Rhythm In Patients Treated With Public Access Defibrillators Over A 10-year Period

Introduction: Previous analysis of emergency medical services manual defibrillator recordings suggests that the proportion of patients with initial shockable rhythms during out-of-hospital cardiac arrest is decreasing over time. This analysis aims to determine if this decline also occurs in public access defibrillator data. Methods: Worldwide post-market data from HeartSine SAM PAD public access defibrillators was collected between 2012 and 2022. Presence of an initial shockable rhythm (ventricular fibrillation or ventricular tachycardia) was determined by the device algorithm decision and clinical overread. The proportion of patients who presented an initial shockable rhythm each year was calculated. Data was analysed using Minitab. Summary statistics were calculated for patient age and gender, and a logistic regression model was used to examine the proportion of initial shockable rhythm over time. Results: A total of 5404 patient events were collected. Seventy-four percent were male, and mean (SD) age was 61.2 (18.2) years. Proportion of initial shockable rhythm as a response to year was assessed, and occurrence of shockable rhythms decreased by approximately 6% per year [OR: 0.94, 95%CI (0.91, 0.96), p&lt;0.001]. Conclusion: In line with findings from emergency service resuscitation attempts, the proportion of initial shockable rhythms in patients treated with a public access defibrillator declined over a ten-year period.

Hypoxia-Inducible Factor-Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs?

Anemia is a common complication of chronic kidney disease; it is mainly treated with erythropoiesis-stimulating agents (ESAs) and iron. Experimental studies extensively investigated the mechanisms involved in the body's response to hypoxia and led to the discovery of the hypoxia-inducible factor (HIF) pathway and the enzymes regulating its function. HIF-prolyl-hydroxyl domain (PHD) inhibitors are a new class of oral drugs developed to treat anemia in chronic kidney disease. By inhibiting the function of PHD enzymes, they mimic the exposure to moderate hypoxia and stimulate the production of endogenous erythropoietin and very likely increase iron availability. Some data also suggest that their efficacy and, consequently, dose needs are less influenced by inflammation than ESAs. Overall, data from phases 2 and 3 clinical development showed efficacy in anemia correction and maintenance for all of the class molecules compared with placebo (superiority) or erythropoiesis-stimulating agents (noninferiority). Three molecules, roxadustat, vadadustat, and daprodustat, underwent extensive clinical investigation to assess their safety on hard cardiovascular end points, mortality, and special interest events (including cancer and thrombosis). Aside from vadadustat in the nondialysis population, at the prespecified primary analyses, all three molecules met the noninferiority margin for the risk of major cardiovascular events compared with erythropoiesis-stimulating agents or placebo. The reason for this discrepancy is difficult to explain. Other safety signals came from secondary analyses of some of the other randomized clinical trials, including a higher incidence of thrombosis. A more extensive clinical experience with post-marketing data on hard safety issues is needed to define better when and how to use HIF-PHD inhibitors compared with already available ESAs.

Patient-related adverse events and device failures associated with commercially available enteral or duodenal self-expanding metal stents: an analysis of the MAUDE database

Duodenal stents are widely used to treat patients with malignant gastric outlet obstruction (MGOO), most commonly from pancreatic cancer. The WallFlex (Boston Scientific, Natick, Mass, USA) and Evolution (Cook Endoscopy, Winston-Salem, NC, USA) duodenal stents are in widespread use for treating MGOO. The objective of this study was to analyze device failures and patient-related adverse events reported to the U.S. Food and Drug Administration (FDA) for these 2 stents. We analyzed postmarketing surveillance data on the WallFlex and Evolution duodenal stents from January 2000 to January 2022 through the FDA's Manufacturer and User Facility Device Experience (MAUDE) database (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm). One hundred fifty-four MAUDE reports were identified and analyzed, from which 176 device failures and 186 patient-related adverse events were identified. Device-related failures for the WallFlex stent were delivery system failure (15.4%) and failure to activate the stent (13.2%). Device failures for the Evolution stent were failure to activate the stent (16.5%) and delivery system failure (15.3%). Patient-related adverse events for the WallFlex stent were perforation (18.9%), death (6.6%), and hemorrhage (3.8%), whereas patient-related adverse events for the Evolution duodenal stent were obstruction (16.3%), perforation (6.3%), aspiration (3.8%), and fragments of broken delivery system left in the patient (3.8%). Both stents are associated with device failures such as failure to activate the stent, stent migration, and occlusion by tumor growth. Despite high success rates, duodenal stents can be associated with serious device failures and patient-related adverse events.

Toxicity signals associated with secukinumab: A pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders. Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post-marketing data. Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0. A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025 /ROR025 = 3.25/9.69), genital candidiasis (IC025 /ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025 /ROR025 = 1.94/4.04) and anosmia (IC025 /ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities. This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high-risk signals need to be given attention.

Focus on zavegepant: the first intranasal third-generation gepant.

Migraine is the leading cause of years lived with disability in people under 50 and its burden is increased by calcitonin gene-related peptide (CGRP)-driven chronicity. Newly approved small molecules that antagonize theCGRP receptor, gepants, have advancedfrom the hepatotoxic first-generation telcagepant tothird-generation intranasal zavegepant;during this process of drug development, rimegepant, ubrogepant and atogepant, which are orally administered, have been launched and approved for clinical usewith no warning for hepatotoxicity. Real-world, long-term postmarketingdata about the efficacy and safety of gepants areawaited. The aim of the present drug evaluation study was to provide an overview of the novel, third-generation intranasal zavegepant, encompassing its development andfuture perspectives.

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

DISSEMINATED HERPES ZOSTER VIRUS INFECTION FOLLOWING BARICITINIB IN COVID-19

P.175 Global FKRP registry - the research database for limb girdle muscular dystrophy R9 (2I)

The Global FKRP Registry is an international registry for individuals with conditions caused by mutation of the Fukutin-Related Protein gene (<i>FKRP</i>): limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and the congenital muscular dystrophies (MD) MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understanding of the natural history and prevalence of FKRP-related MD and to aid the rapid identification of eligible patients for clinical studies. It disseminates FKRP-relevant information; provides a source of information to academics, industry and healthcare professionals; and supports the FKRP community. Registration is patient-initiated through a secure online portal (www.fkrp-registry.org). Participants give their consent and are invited to complete a questionnaire about their condition. Data is reported by both patients and their healthcare professionals and includes gene mutation, age of onset, presenting symptoms, motor function and muscle strength, respiratory and cardiac function, and medication. In addition, participants are invited to complete validated questionnaires on quality of life (INQoL) and pain (McGill). In recent years, the registry has assisted recruitment to natural history studies and clinical trials in LGMDR9. It has facilitated research by responding to data enquiries and circulating surveys, demonstrating its effectiveness as a repository of patient data, a tool for data collection and assembly of a trial-ready patient cohort. This year, the registry will implement the newly developed TREAT-NMD LGMD Core Dataset. Collection of a shared dataset by individual LGMD patient registries from around the world will enable a larger and potentially more powerful body of data to be collected on this diverse patient cohort. As knowledge of rare neuromuscular conditions increases and advances in the development of potential therapies are made, the registry is centrally placed to help support the accumulation of natural history and post-marketing surveillance data and facilitate recruitment to clinical trials.