Abstract:Introduction Although the burden of adverse drug reactions (ADRs) has a significant impact on patients' quality of life, thorough knowledge about patients' perspectives on the burden of ADRs attributed to biologics is lacking. Objectives This study was conducted to gain insight into the patient burden of ADRs experienced with biologic use. Methods The Dutch Biologic Monitor is a prospective, multicentre, event monitoring cohort system including information collected by web-based questionnaires from patients us… Show more
“… Rapid defervescence. Possible resistant viral mutations can alter mAb affinities and efficacy Adverse drug reactions are severe and often life-threatening Varying bioavailabilities may affect effectivness Affordability and accessibility across global economic spectrum and lower income countries is questionable 112 , 167–171 …”
Section: Introductionmentioning
confidence: 99%
“… 112 However, cytokine-targeting mAbs are also documented to be potentially associated with adverse events. 169 This may impact both the outcomes of clinical trials and post-approval use in critically ill COVID-19 patients, particularly those with comorbidities. Figure 2.…”
Section: Introductionmentioning
confidence: 99%
“…A questionnaire-based survey involving 1,355 patients who were undergoing treatment with cytokine-targeting mAbs for immune-mediated inflammatory diseases identified several risks associated with the immunotherapy. 169 Those patients were treated with various therapeutic mAbs including adalimumab, canakinumab, infliximab, rituximab, sarilumab, and tocilizumab. In several patients, the treatment was associated with minor adverse events such as respiratory disorders, nervous system disorders, or cancer in patients with no comorbidities.…”
Section: Introductionmentioning
confidence: 99%
“…In several patients, the treatment was associated with minor adverse events such as respiratory disorders, nervous system disorders, or cancer in patients with no comorbidities. 169 However, in patients with preexisting comorbidities such as inflammatory rheumatic diseases, 49% (665/1,355) reported adverse drug reactions (ADRs). 169 In total, approximately 1,720 ADRs were reported in patients with comorbidities, with 65% (1,116 ADRs) being musculoskeletal complaints, injection-site reactions, infections, skin reactions, fatigue, and gastrointestinal complications.…”
Section: Introductionmentioning
confidence: 99%
“… 169 However, in patients with preexisting comorbidities such as inflammatory rheumatic diseases, 49% (665/1,355) reported adverse drug reactions (ADRs). 169 In total, approximately 1,720 ADRs were reported in patients with comorbidities, with 65% (1,116 ADRs) being musculoskeletal complaints, injection-site reactions, infections, skin reactions, fatigue, and gastrointestinal complications. 169 Moreover, of the patients who developed treatment-associated ADRs, 29 (4%) required hospitalization.…”
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease 2019 (COVID-19) pandemic that lacks globally accessible effective antivirals or extensively available vaccines. Numerous clinical trials are exploring the applicability of repurposed monoclonal antibodies (mAbs) targeting cytokines that cause adverse COVID-19-related pathologies, and novel mAbs directly targeting SARS-CoV-2. However, comorbidities and the incidence of cytokine storm (CS)-associated pathological complexities in some COVID-19 patients may limit the clinical use of these drugs. Additionally, CS-targeting mAbs have the potential to cause adverse events that restrict their applicability in patients with comorbidities. Novel mAbs targeting SARS-CoV-2 require pharmacological and toxicological characterization before a marketable product becomes available. The affordability of novel mAbs across the global economic spectrum may seriously limit their accessibility. This review presents a perspective on antibody-based research efforts and their limitations for COVID-19.
“… Rapid defervescence. Possible resistant viral mutations can alter mAb affinities and efficacy Adverse drug reactions are severe and often life-threatening Varying bioavailabilities may affect effectivness Affordability and accessibility across global economic spectrum and lower income countries is questionable 112 , 167–171 …”
Section: Introductionmentioning
confidence: 99%
“… 112 However, cytokine-targeting mAbs are also documented to be potentially associated with adverse events. 169 This may impact both the outcomes of clinical trials and post-approval use in critically ill COVID-19 patients, particularly those with comorbidities. Figure 2.…”
Section: Introductionmentioning
confidence: 99%
“…A questionnaire-based survey involving 1,355 patients who were undergoing treatment with cytokine-targeting mAbs for immune-mediated inflammatory diseases identified several risks associated with the immunotherapy. 169 Those patients were treated with various therapeutic mAbs including adalimumab, canakinumab, infliximab, rituximab, sarilumab, and tocilizumab. In several patients, the treatment was associated with minor adverse events such as respiratory disorders, nervous system disorders, or cancer in patients with no comorbidities.…”
Section: Introductionmentioning
confidence: 99%
“…In several patients, the treatment was associated with minor adverse events such as respiratory disorders, nervous system disorders, or cancer in patients with no comorbidities. 169 However, in patients with preexisting comorbidities such as inflammatory rheumatic diseases, 49% (665/1,355) reported adverse drug reactions (ADRs). 169 In total, approximately 1,720 ADRs were reported in patients with comorbidities, with 65% (1,116 ADRs) being musculoskeletal complaints, injection-site reactions, infections, skin reactions, fatigue, and gastrointestinal complications.…”
Section: Introductionmentioning
confidence: 99%
“… 169 However, in patients with preexisting comorbidities such as inflammatory rheumatic diseases, 49% (665/1,355) reported adverse drug reactions (ADRs). 169 In total, approximately 1,720 ADRs were reported in patients with comorbidities, with 65% (1,116 ADRs) being musculoskeletal complaints, injection-site reactions, infections, skin reactions, fatigue, and gastrointestinal complications. 169 Moreover, of the patients who developed treatment-associated ADRs, 29 (4%) required hospitalization.…”
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease 2019 (COVID-19) pandemic that lacks globally accessible effective antivirals or extensively available vaccines. Numerous clinical trials are exploring the applicability of repurposed monoclonal antibodies (mAbs) targeting cytokines that cause adverse COVID-19-related pathologies, and novel mAbs directly targeting SARS-CoV-2. However, comorbidities and the incidence of cytokine storm (CS)-associated pathological complexities in some COVID-19 patients may limit the clinical use of these drugs. Additionally, CS-targeting mAbs have the potential to cause adverse events that restrict their applicability in patients with comorbidities. Novel mAbs targeting SARS-CoV-2 require pharmacological and toxicological characterization before a marketable product becomes available. The affordability of novel mAbs across the global economic spectrum may seriously limit their accessibility. This review presents a perspective on antibody-based research efforts and their limitations for COVID-19.
The aim of the study is to characterise safety signals based on the Dutch spontaneous reporting system (SRS) and to investigate the association between signal characteristics and Product Information (PI) update stratified by approval type: centrally authorised products (CAPs) versus nationally and decentralised authorised products (NAPs). Methods: This study evaluates the full cohort of signals disseminated from the Dutch SRS in the period from 2008 to 2017. Each retrieved signal was characterised on a number of aspects. The signal management process from signal generation to a potential PI update was analysed in four steps: (1) signal characterisation; (2) proposed actions by the Dutch national competent authority (NCA) for the signals;(3) presence of PI update (yes/no) and association with signal characteristics;(4) timing from the moment the signal was issued to PI update. For step 1-3 we stratified products in CAPs and NAPs.Results: Of all signals, 88.7% led to a proposed regulatory action by the NCA. Signals from the Dutch SRS for CAPs versus NAPs more often concerned biologicals, important medical events, class effects and shorter periods since marketing authorization.We detected PI updates for 26.2% of CAP signals and 61.3% of NAP signals.
Conclusions:The Dutch SRSs remains an important source of signals. There are some notable differences in the characteristics of signals for CAPs versus NAPs. Signals for NAPs more frequently led to PI updates.
Why is this important?While previous studies showed that the characteristics of drug safety signals from a variety of sources may affect regulatory actions, there is little information on how characteristics of safety signals derived specifically from national spontaneous reporting systems are associated with regulatory actions. The aim of the study is to characterise signals based on the Dutch spontaneous reporting system and to investigate the association between signal characteristics and Product Information updates for products with a centralised marketing authorization and those without.
Background
The number of Individual Case Safety Reports (ICSRs) in pharmacovigilance databases are rapidly increasing world‐wide. The majority of ICSRs at the Netherlands Pharmacovigilance Centre Lareb is reviewed manually to identify potential signal triggering reports (PSTR) or ICSRs which need further clinical assessment for other reasons.
Objectives
To develop a prediction model to identify ICSRs that require clinical review, including PSTRs. Secondly, to identify the most important features of these reports.
Methods
All ICSRs (n = 30 424) received by Lareb between October 1, 2017 and February 26, 2021 were included. ICSRs originating from marketing authorisation holders and ICSRs reported on vaccines were excluded. The outcome was defined as PSTR (yes/no), where PSTR ‘yes’ was defined as an ICSR discussed at a signal detection meeting. Nineteen features were included, concerning structured information on: patients, adverse drug reactions (ADR) or drugs. Data were divided into a training (70%) and test set (30%) using a stratified split to maintain the PSTR/no PSTR ratio. Logistic regression, elastic net logistic regression and eXtreme Gradient Boosting models were trained and tuned on a training set. Random down‐sampling of negative controls was applied on the training set to adjust for the imbalanced dataset. Final models were evaluated on the test set. Model performances were assessed using the area under the curve (AUC) with 95% confidence interval of a receiver operating characteristic (ROC), and specificity and precision were assessed at a threshold for perfect sensitivity (100%, to not miss any PSTRs). Feature importance plots were inspected and a selection of features was used to re‐train and test model performances with fewer features.
Results
1439 (4.7%) of reports were PSTR. All three models performed equally with a highest AUC of 0.75 (0.73–0.77). Despite moderate model performances, specificity (5%) and precision (5%) were low. Most important features were: ‘absence of ADR in the Summary of product characteristics’, ‘ADR reported as serious’, ‘ADR labelled as an important medical event’, ‘ADR reported by physician’ and ‘positive rechallenge’. Model performances were similar when using only nine of the most important features.
Conclusions
We developed a prediction model with moderate performances to identify PSTRs with nine commonly available features. Optimisation of the model using more ICSR information (e.g., free text fields) to increase model precision is required before implementation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
