-
JACC. CardioOncology Dec 2022T-cell therapies, such as chimeric antigen receptor (CAR) T-cell, bispecific T-cell engager (BiTE) and tumor-infiltrating lymphocyte (TIL) therapies, fight cancer cells... (Review)
Review
T-cell therapies, such as chimeric antigen receptor (CAR) T-cell, bispecific T-cell engager (BiTE) and tumor-infiltrating lymphocyte (TIL) therapies, fight cancer cells harboring specific tumor antigens. However, activation of the immune response by these therapies can lead to a systemic inflammatory response, termed cytokine release syndrome (CRS), that can result in adverse events, including cardiotoxicity. Retrospective studies have shown that cardiovascular complications occur in 10% to 20% of patients who develop high-grade CRS after CAR T-cell therapy and can include cardiomyopathy, heart failure, arrhythmias, and myocardial infarction. While cardiotoxicities have been less commonly reported with BiTE and TIL therapies, systematic surveillance for cardiotoxicity has not been performed. Patients undergoing T-cell therapies should be screened for cardiovascular conditions that may not be able to withstand the hemodynamic perturbations imposed by CRS. Generalized management of CRS, including the use of the interleukin-6 antagonist, tocilizumab, for high-grade CRS, is used to mitigate the risk of cardiotoxicity.
PubMed: 36636447
DOI: 10.1016/j.jaccao.2022.07.014 -
Respiratory Research Apr 2022In the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity compared... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity compared with placebo, with side-effects that were manageable for most patients. We used data from the INBUILD trial to characterize further the safety and tolerability of nintedanib.
METHODS
Patients with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), who had experienced progression of ILD within the 24 months before screening despite management deemed appropriate in clinical practice, were randomized to receive nintedanib 150 mg twice daily or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg twice daily. We assessed adverse events and dose adjustments over the whole trial.
RESULTS
A total of 332 patients received nintedanib and 331 received placebo. Median exposure to trial drug was 17.4 months in both treatment groups. Adverse events led to treatment discontinuation in 22.0% of patients treated with nintedanib and 14.5% of patients who received placebo. The most frequent adverse event was diarrhea, reported in 72.3% of patients in the nintedanib group and 25.7% of patients in the placebo group. Diarrhea led to treatment discontinuation in 6.3% of patients in the nintedanib group and 0.3% of the placebo group. In the nintedanib and placebo groups, respectively, 48.2% and 15.7% of patients had ≥ 1 dose reduction and/or treatment interruption. Serious adverse events were reported in 44.3% of patients in the nintedanib group and 49.5% of patients in the placebo group. The adverse event profile of nintedanib was generally consistent across subgroups based on age, sex, race and weight, but nausea, vomiting and dose reductions were more common among female than male patients.
CONCLUSIONS
The adverse event profile of nintedanib in patients with progressive fibrosing ILDs other than IPF is consistent with its established safety and tolerability profile in patients with IPF and characterized mainly by gastrointestinal events, particularly diarrhea. Management of adverse events using symptomatic therapies and dose adjustment is important to minimize the impact of adverse events and help patients remain on therapy. Trial registration Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178 A video abstract summarizing the key results presented in this manuscript is available at: https://www.globalmedcomms.com/respiratory/cottin/INBUILDsafety .
Topics: Diarrhea; Disease Progression; Female; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Diseases, Interstitial; Male; Protein Kinase Inhibitors; Treatment Outcome
PubMed: 35392908
DOI: 10.1186/s12931-022-01974-2 -
Vaccine Sep 2020COVID-19 vaccines are the most important tool to stem the pandemic. They are being developed with unprecedented global collaboration and accelerated timelines to achieve...
COVID-19 vaccines are the most important tool to stem the pandemic. They are being developed with unprecedented global collaboration and accelerated timelines to achieve WHO Emergency Use Listing, while using regulatory pathways through national regulatory authorities. Alongside preparations to ensure equitable access to the vaccines among people globally, preparations must be made within countries for COVID-19 vaccines safety surveillance on an urgent basis. Safety surveillance must be capable of investigating adverse events of special interest (AESI) and adverse events following immunization to determine a change in the benefit-risk profile of the vaccine, and to be able to anticipate coincidental events that might be attributed to the vaccine. Active surveillance systems should calculate the incidence of background rates of AESI prior to vaccine roll out. These background rates vary tremendously across regions, populations and case ascertainment methods. Active surveillance systems must be established or strengthened now, (including in LMIC), to calculate the background rates. Utilizing standardized case definitions and global standards for AESI will help in harmonization. Vaccine safety communication plans should be developed. Expanding the global vaccine safety system to meet the needs of COVID-19 and other emergency and routine use vaccines is a priority currently.
Topics: Adverse Drug Reaction Reporting Systems; Betacoronavirus; COVID-19; COVID-19 Vaccines; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; Product Surveillance, Postmarketing; SARS-CoV-2; Vaccination; Viral Vaccines
PubMed: 32684499
DOI: 10.1016/j.vaccine.2020.07.013 -
Endocrinology, Diabetes & Metabolism... Sep 2021Recombinant human growth hormone therapy (rhGH) has been available since 1985 for a variety of conditions and has expanded the indications for rhGH therapy and the...
SUMMARY
Recombinant human growth hormone therapy (rhGH) has been available since 1985 for a variety of conditions and has expanded the indications for rhGH therapy and the number of patients receiving therapy. The very nature of the therapy exposes individuals to years of injections. There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy. We report nine cases of localized lipoatrophy during rhGH therapy accounting for 14.5% of patients taking rhGH presenting to a single centre for routine follow-up over just a 2-month period. The development of localized lipoatrophy does not appear to be age, indication or dose-related but rather related to repeated administration of rhGH into a limited number of sites. The most likely putative mechanism is the local lipolytic action of growth hormone (GH) itself, although the possibility of an excipient-based interaction cannot be excluded. Given the high prevalence of this adverse event and the potential to prevent it with adequate site rotation, we can recommend that patients be informed of the possible development of localized lipoatrophy. Doctors and nurses should closely examine injection sites at each visit, and site rotation should be emphasized during injection technique education.
LEARNING POINTS
There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy. Examination of the injection sites at each visit by the treating healthcare practitioner. To advise the parents/caregivers/patients to change their injection site with each injection. To advise the parents/caregivers/patients to change the needles after every use. For parents, caregivers and patients to self-inspect their injection sites and have a high alert for the development of lipoatrophy and to then immediately report it to their doctor.
PubMed: 34515656
DOI: 10.1530/EDM-21-0087 -
Journal of Diabetes Science and... Jun 2023Adverse events for continuous glucose monitors (CGMs) represent a significant issue for people with diabetes with 281 963 CGM adverse events occurring in 2022. The...
BACKGROUND
Adverse events for continuous glucose monitors (CGMs) represent a significant issue for people with diabetes with 281 963 CGM adverse events occurring in 2022. The process to obtain adverse events and the US Food and Drug Administration (FDA) database that contains them are reviewed.
METHODS
Tables were created in SQL Server for four CGM products (Dexcom G6, all versions of Abbott Libre, Medtronic Guardian 3, and Senseonics Eversense) containing either malfunction or injury adverse events sorted by the manufacturer's chosen product code. As the product code is not always clear (or appropriate), the causes of the events were determined from the text description of the adverse event. The resulting causes were listed in decreasing order in tables for each product and event type.
RESULTS
A common effect of several event causes prevented the user from obtaining a result. Inaccuracy was also a frequent complaint. Other causes were specific to that device.
CONCLUSIONS
Creating tables based on manufacturer problem codes for their CGMs, followed by analysis of the adverse event text, facilitates the analysis of event causes. Analyzing adverse event data is the first step in trying to reduce the number of adverse events.
PubMed: 37264590
DOI: 10.1177/19322968231178525 -
British Journal of Clinical Pharmacology Mar 2021Medication harm has negative clinical and economic consequences, contributing to hospitalisation, morbidity and mortality. The incidence ranges from 4 to 14%, of which...
AIMS
Medication harm has negative clinical and economic consequences, contributing to hospitalisation, morbidity and mortality. The incidence ranges from 4 to 14%, of which up to 50% of events may be preventable. A predictive model for identifying high-risk inpatients can guide a timely and systematic approach to prioritisation. The aim of this study is to develop and internally validate a risk prediction model for prioritisation of hospitalised patients at risk of medication harm.
METHODS
A retrospective cohort study was conducted in general medical and geriatric specialties at an Australian hospital over six months. Medication harm was identified using International Classification of Disease (ICD-10) codes and the hospital's incident database. Sixty-eight variables, including medications and laboratory results, were extracted from the hospital's databases. Multivariable logistic regression was used to develop the final risk model. Performance was evaluated using area under the receiver operative characteristic curve (AuROC) and clinical utility was determined using decision curve analysis.
RESULTS
The study cohort included 1982 patients with median age 74 years, of which 136 (7%) experienced at least one adverse medication event(s). The model included: length of stay, hospital re-admission within 12 months, venous or arterial thrombosis and/or embolism, ≥ 8 medications, serum sodium < 126 mmol/L, INR > 3, anti-psychotic, antiarrhythmic and immunosuppressant medications, and history of medication allergy. Validation gave an AuROC of 0.70 (95% CI: 0.65-0.74). Decision curve analysis identified that the AIME may be clinically useful to help guide decision making in practice.
CONCLUSION
We have developed a predictive model with reasonable performance. Future steps include external validation and impact evaluation.
Topics: Aged; Area Under Curve; Australia; Cohort Studies; Humans; Inpatients; Retrospective Studies
PubMed: 32986855
DOI: 10.1111/bcp.14560 -
GE Portuguese Journal of... Jul 2019Immune checkpoint inhibitors have shown anti-tumour activity in cancers such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma,... (Review)
Review
Immune checkpoint inhibitors have shown anti-tumour activity in cancers such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma, colorectal cancer, and Hodgkin's lymphoma. Though immune checkpoint inhibitors have revolutionized the treatment and prognosis of some advanced malignancies, they are also associated with a significant risk of immune-related adverse events. These adverse events can occur in any organ system, but gastrointestinal side effects are among the most commonly reported, with manifestations ranging from mild diarrhoea to severe colitis, sharing some features with inflammatory bowel disease. Anticipating a greater use of these drugs in the future, gastroenterologists should expect to be increasingly faced with gastrointestinal immune-related adverse events. Knowledge of these toxicities, as well as effective management algorithms, is essential to enable early diagnosis and treatment, decreasing morbidity and mortality. We reviewed the currently available literature on gastrointestinal toxicity induced by immune checkpoint inhibitors, namely the clinical features, diagnosis, and management.
PubMed: 31328141
DOI: 10.1159/000494569 -
International Journal of Clinical... Apr 2024Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients...
Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database.
BACKGROUND
Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications.
AIM
To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide.
METHOD
All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics.
RESULTS
During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression.
CONCLUSION
Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.
Topics: Male; Humans; Female; Liraglutide; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Pharmacovigilance; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptides; Gastric Inhibitory Polypeptide
PubMed: 38265519
DOI: 10.1007/s11096-023-01694-7 -
Journal For Immunotherapy of Cancer Jul 2021Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation....
BACKGROUND
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.
METHODS
Two adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial's protocol. Databases were queried up to May 19, 2020.
RESULTS
In the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0-16, serious adverse events database: median 11 weeks, IQR 6-21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1-2) and grade 2 (moderate) (IQR 2-3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.
CONCLUSIONS
This is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.
Topics: Adult; Aged; Eye Diseases; Humans; Immune Checkpoint Inhibitors; Middle Aged; Programmed Cell Death 1 Receptor; Retrospective Studies
PubMed: 34226280
DOI: 10.1136/jitc-2020-002119 -
Current Drug Safety 2022The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of...
BACKGROUND
The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of pemafibrate in clinical settings, a pilot study evaluating the association between drug use and detected events was performed in Japan.
AIMS
In this study, the association between detected events and the use of pemafibrate, utilizing pharmacy records maintained by community pharmacists, was investigated. We identified the newuser cohort using a test and active comparison drug and collected the baseline information. An active comparison group comprising new users was used to assess the events.
METHODS
A retrospective cohort study using questionnaires regarding baseline and event data was conducted by community pharmacists belonging to the Japan Pharmaceutical Association. The incidence of event and estimated hazard ratio were calculated using the Cox proportional hazards model that was adjusted for confounding factors, such as age and sex.
RESULTS
A total of 1294 patients using pemafibrate and 508 patients using fenofibrate were identified as new drug users. The most reported events involving suspected adverse reactions and add-on drugs were increased blood pressure and lipid-lowering effects with pemafibrate use, and nasopharyngitis, pruritus, dizziness, and lipid-lowering effects with fenofibrate use. No significant differences were found in commonly occurring events, except that an add-on anti-hypertensive drug has been used by pemafibrate users compared to fenofibrate users.
CONCLUSION
This study conducted by pharmacists can facilitate the safety assessment of newly marketed drugs, as few drug use investigations with a comparator are carried out by the Japanese authority for pharmaceutical companies. However, further research is required.
Topics: Benzoxazoles; Butyrates; Fenofibrate; Humans; Japan; Pharmaceutical Preparations; Pharmacists; Pilot Projects; Retrospective Studies
PubMed: 35209830
DOI: 10.2174/1574886317666220224142511