Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Systematic review on the adverse reactions of oral administration of Indigo Naturalis and its preparations

Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study,we aimed to determine the incidence of adverse drug reactions(ADRs)of atezolizumab,identify ADR signals that are significantly related to atezolizumab,and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events(ADEs)reported in the American Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database.Methods In total,4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed.Results The top three ADEs were febrile neutropenia(3.7%),anemia(2.9%),and acute renal failure(2.3%).In addition,the incidence rates of some ADEs were significantly different according to sex and age.The systematic organ classification of atezolizumab ADEs involved 32 systems,among which the top three were blood and lymphatic system disorders(585 cases,12.2%),gastrointestinal disorders(433 cases,9.0%),and infections and infestations(401 cases,8.4%).The reporting odds ratio(ROR)method was used to detect the ADR signals of atezolizumab.The ROR(95%confidence interval)of the top ADE,febrile neutropenia,was 39.236(33.757–45.604).In addition,we found 121 cases of complications associated with immune-related ADEs.Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use,suggesting that atezolizumab has an acceptable and controllable drug effect.

Clinical profile of medication-related emergencies among patients presenting to the emergency department:An observational study

Objective:To determine the clinical profile of patients presenting with medication-related emergencies to the Emergency Department of our institute.Methods:This was an observational study conducted between November 2018 and September 2020 at Bangalore Baptist Hospital,Karnataka.A total of 138 subjects who satisfied the inclusion criteria were included in the study.The severity of adverse drug reactions(ADR)is assessed based on the Hurwitz severity assessment scale of ADR.Glasgow coma scale at the time of presentation and source of medication were noted.The type of drug overdose,requirement of advanced airway and vasopressors,and the outcome were also assessed.Results:Among medication-related emergencies(n=138)in our study,ADR contributed to 70.3%(n=97)of the study population,and drug overdose accounted for 29.7%(n=41).One-third of the ADR occurred in patients aged above 60 years.Most patients were hemodynamically stable and did not require vasopressors,or advanced airway in both groups.Most patients had Glasgow coma scale ranging from 13-15 in both groups.Nonsteroidal anti-inflammatory drugs were the most used medicine(17/41,41.5%)and most medications were over the counter drugs(25/41,61.0%)in the drug overdose group;meanwhile in the ADR group,anti-diabetic medication was the most used medicine(34/97,35.1%)and most medications were prescribed in the ADR group(93/97,95.9%).Conclusions:Our study shows that ADR is the most common type of medication-related emergency.

Immune checkpoint inhibitor-related hepatotoxicity:A review

The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer:Gemcitabine monotherapy vs combination chemotherapy

BACKGROUND Combination chemotherapy(gemcitabine plus nab-paclitaxel and FOLFIRINOX)is widely used as the standard first-line treatment for pancreatic cancer.Considering the severe toxicities of combination chemotherapy,gemcitabine monotherapy(G mono)could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status.However,reports on the efficacy of G mono in patients older than 75 years are limited.AIM To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.METHODS We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono(n=45)or combination therapy(n=59)as a first-line treatment between 2011 and 2019.All patients were histologically diagnosed with ductal adenocarcinoma.Primary outcomes were progression-free survival and overall survival.We also analyzed subgroups according to age[65-74 years(elderly)and≥75 years(very elderly)].Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.RESULTS The baseline characteristics were significantly different between the two chemotherapy groups,especially regarding age,ratio of multiple metastases,tumor burden,and Eastern Cooperative Oncology Group performance status.After propensity score matching,the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients.In the elderly patients,the median progression-free survival(62 d vs 206 d,P=0.000)and overall survival(102 d vs 302 d,P=0.000)were longer in the combination chemotherapy group.However,in the very elderly patients,the median progression-free survival(147 d and 174 d,respectively,P=0.796)and overall survival(227 d and 211 d,respectively,P=0.739)were comparable between the G mono and combination chemotherapy groups.Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group,especially thromboembolism(G mono vs nab-paclitaxel vs FOLFIRINOX;8.9%vs 5.9%vs 28%,P=0.041),neutropenia(40.0%vs 76.5%vs 84.0%,P=0.000),and neuropathy(0%vs 61.8%vs 28.0%,P=0.006).CONCLUSION In elderly patients,combination therapy is more effective than G mono.However,G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

Use of Cholesterol-Lowering Medications of Patients with Myocardial Infarction from 2007-2015 in Cardiology Clinic to “Mother Teresa” University Hospital in Albania

Background: Coronary Heart Disease (CHD) remains the leading cause of morbidity and mortality in Albania. According to Institute of Statistics of Albania (ISA), CHD remains in the 5 first places caused mortality and morbidity in our country. Currently, all the protocol treatments to Mother Teresa University Hospital (MTUH) are focused on low-density lipoprotein cholesterol (LDL-C) as the primary target for risk reduction therapy, followed by triglycerides (TG) and high-density lipoprotein cholesterol (HDL). Our clinicians recommend that the intensity and target goals of LDL-C-lowering therapy should be adjusted to individual treatment. The choice of a specific drug from anti hypercholesterolemia class depends on several factors which need to be evaluated better from our health providers. Methods and Findings: Data was collected between 2007 to 2015 at Mother Teresa University Hospital (MTUH), Intensive Care Unit in Cardiology Clinic. 700 patients were treated with statins as follows: Fluvastain 40 mg and 80 mg, Atorvastatin 10 mg and 20 mg, Simvastatin and Rosuvastatin 20 mg. Statins are increased significantly during the years compared with fibrates. Their use grew from 87% of all statin types to 95% in 2015, with different types from fluvastatin in 2007 to atorvastatin being the leading medication in 2015. Coronary Heart Disease, especially Myocardium Infarct, were studied as diseases when meanly the hypolipidic drugs were usually used in medical protocol treatment. Statins and fibrates were the therapy target to be studied when statin dominated the patients’ treatment and fibrates were used in limited quantity. Atorvastatin is now dominating the market, while fluvastatin was on the first statin therapy for several years in the past. Fibrate were used in the modest quantities in value from 2% to 1.5% in years 2007 to 2015. The use of statins in moderate-risk and high-risk patients showed continued growth subsequently, but stable with dosage of atorvastatin 20 mg. Lower statin dosage used was independently associated for all patients, young patients had used high dosage of statins and fluvastatin respectively 40 mg and 80 mg. The missing high dosage of atorvastatin was notable. The values of LDL were improved but not in the level of efficacy of treatment. Conclusion: Statin therapy becomes more selected compared with fibrate. Atorvastatin 20 mg remains the most important stain used in our clinic, but low dosage remains still a problem. The expected level of LDL-C is the target for the practitioners. More aggressive statins such as rosuvastatin start to be present in our clinic, but it is less used by the patients. Meanwhile the lifestyle, exercises, balance diet, smoking cessation are parts of the patients’ files. The side effects are minors and the medication process has continued.

Impact of an Active Pharmacovigilance Program in a Third-Level Clinic in Barranquilla, Colombia

The objective of this study is to assess the impact of APV （active pharmacovigilance） and PPV （passive pharmacovigilance） by detection of ADEs （adverse drug events）, through PIs （pharmaceutical interventions）. Authors have used observational pre-post intervention study. Dader methodology was used in 123 patients with data obtained from medical records and pharmaceutical interview. Detection of ADE was made by direct observation and laboratory tests, with statistical significance 0.05. In PPV, 47 ADEs were detected： nausea, vomiting, skin rash and skin redness. In APV, 100 ADEs are presented, similar to those described in the PPV, in which Dipyrone produced 26.2%. The causes of DRPs （drug related problems） were： probability of adverse events 36%, personal characteristics 30%, and dose regimen and/or inadequate duration 22%. Out of 127 PIs performed, 91.34% were accepted and resolved. The patient satisfaction rate was 82.7% for APV and doctor satisfaction 90.4% with high impact, surpassing the 80%. The impact of APV was 93.6% and 53% in PPV for PIs and ADEs. PIs were performed to the ADEs with a high percentage of accepted and solved ones. Evaluation of satisfaction of patients and doctors in APV had a high impact. The assessment of APV generated a high impact on compliance and PPV a low one.