Rate Of Adverse Drug Reactions Research Articles

REAL-WORLD TREATMENT BURDEN ASSOCIATED WITH PARENTERAL ON-DEMAND THERAPIES FOR HEREDITARY ANGIOEDEMA

<h3>Introduction</h3> The objective of the current study is to describe treatment burden associated with FDA-approved on-demand therapies for hereditary angioedema (HAE) attacks using the real-world frequency of administration site reactions reported in the FDA's Adverse Event Reporting System (FAERS). <h3>Method</h3> : We searched FAERS data from 10/01/2009 to 3/31/2021 for human C1-inhibitor (H-C1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (R-C1-INH). The number of administration site adverse drug reactions (ADRs), where the drug was listed as "primary suspect" were recorded for each drug. ADR preferred terms were then grouped into an ADR domain based on semantic and/or clinical similarity. This process resulted in 15 overarching ADR domains. For each ADR domain, the number of reports for each drug were calculated per year from the time of their approval through March 2021. Descriptive results are presented. <h3>Results</h3> The most frequently reported ADR domains included injection site pain, erythema, swelling as well as access site complications or malfunctions. Icatibant had the highest rate of ADRs per year for site pain (16.6), erythema (7.08), and swelling (6.35). Access site complications/malfunctions (7.75) were highest for R-C1-INH. ADR rates per year for H-C1-INH and ecallantide were under 2. <h3>Conclusion</h3> Results generally support those found in clinical trials, particularly for icatibant, for which 97% of patients experience injection-site reactions. ADR rates are not exposure-adjusted and are based on spontaneous reporting. These real-world descriptive results suggest that patients experience significant treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks.

How Low Is Too Low? A Retrospective Analysis of Very Low LDL-C Levels in Veterans.

Low-density lipoprotein cholesterol (LDL-C) can build up on the walls of blood vessels, leading to coronary heart disease. Medications used to lower LDL-C levels have demonstrated decreased risks of atherosclerotic cardiovascular disease, but currently, there is no consensus on how to define very low LDL-C levels. It is necessary for the body to have LDL-C to maintain proper brain function; however, the safety and effects of prolonged very low LDL-C levels are unknown. The current study sought to gather information to determine the risks of very low LDL-C levels in a veteran population. A retrospective chart review was conducted at a US Department of Veterans Affairs medical center. Patients with hyperlipidemia/dyslipidemia treated with HMG-CoA reductase inhibitors or proprotein convertase subtilisin/kexin type 9 (PCSK9) therapy and LDL-C levels < 40 mg/dL between January 1, 2010, and September 1, 2020, were included. The primary outcome was the rate of intracranial hemorrhage that could be caused by an LDL-C level < 40 mg/dL. The secondary outcomes included actions taken by clinicians, adverse drug reactions (ADRs), duration of therapy, and medication adherence. This study included 3027 patients. Of the included patients, 8 had an intracranial hemorrhage within 1 year from a documented LDL-C level < 40 mg/dL (0.26%). Thirty-two patients with an LDL-C level < 40 mg/dL did not have a documented ADR with the studied medications. Of the 32 charts, 26 had a clinician address the LDL-C level < 40 mg/dL with either documentation and/or modification of the medication prescribed. The most common ADRs among the studied medications were muscle and joint pain, rash, and cramps. Adherence to the medications was consistently similar for all studied medications. Of the patient population included in this study, 0.26% of patients had an intracranial hemorrhage within 1 year of having an LDL-C level < 40 mg/dL. The rate of ADRs related to the medications analyzed in this study shows no statistical significance (P > .05). When compared with low- and moderate-intensity statin medications, high-intensity statin medications were statistically significant in resulting in an LDL-C level < 40 mg/dL (P < .001). LDL-C levels < 40 mg/mL were not routinely documented as being addressed in the chart by the clinician.

Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn's Disease: Results from an Early Access Program in Brazil.

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

A study of adverse drug reactions in tuberculosis patients in a tertiary care hospital

Background: Tuberculosis is the most rambling communicable infectious disease on earth. It is the single most common cause of death in individuals aged 15-49 years. Adverse drug reactions to antitubercular drugs causing significant morbidity, mortality, incurring substantial additional costs because of added outpatient visits, tests, and hospitalizations. Study was carried out with objectives of assessing the rate and type of adverse drug reactions (ADRs) and detecting serious and preventable ADRs with collection of demographic details of patients taking antitubercular drugs and developing ADRS.Methods: A cross sectional, prospective, observational study conducted in department of chest and TB of a tertiary Health care and teaching hospital in both IPD and OPD patients for a period of 18 months. 480 patients monitored.Results: Among 480 patients 120 i.e., 25% developed ADR. frequency being significantly higher in males (58%) and adult age group (&gt;18 years) amongst hospitalized comparing to outdoor patients the gastrointestinal tract [GIT] (39%) followed by, generalized body disorders (19%) hepatobiliary system (17%) were organ systems most affected Majority (56%) ADRs reported in 0-2 month of starting therapy (63%) of cases were in “probable according to Naranjo causality assessment (37%) being possible. 55% ADRs were moderate in severity followed by 36% mild and 9% severe. 30% of ADRs were definitely preventable followed by 20% of probably prevented according to schumock thronstone preventability scaleConclusions: Study highlights the importance of routine monitoring and robust pharmacovigilance system for success of national tuberculosis programmes in India as well as worldwide.

Nirmatrelvir/Ritonavir and Molnupiravir in the Treatment of Mild/Moderate COVID-19: Results of a Real-Life Study.

Molnupiravir and nirmatrelvir were the first available oral antivirals (OAs) active against SARS-CoV-2. Trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy in order to provide real-life data on the efficacy and safety of OAs during the omicron surge of the COVID-19 pandemic. Among 257 patients, 56.8% received molnupiravir, while 43.2% received nirmatrelvir/ritonavir. Patients in the molnupiravir group were older, had a lower body mass index, and had a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. Three hospitalizations were recorded in the molnupiravir (2.1%) group and one in the nirmatrelvir/ritonavir (0.9%) group. One patient treated with molnupiravir died. The median time to negativity was 8 days in the nirmatrelvir/ritonavir group vs. 10 days in the molnupiravir group, p < 0.01. We recorded 37 ADRs (mainly dysgeusia, diarrhea, and nausea) in 31 individuals (12.1%). Only two patients (0.8%) treated with molnupiravir terminated treatment due to ADRs. In conclusion, in a population of mostly vaccinated patients treated with OAs, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were lower than those reported in pivotal trials.

Assessment of Knowledge, Attitude, and Practice of Physicians toward Pharmacovigilance in Public and Private Hospitals in Jordan

Knowledge, attitude, and practice toward pharmacovigilance (PV) among healthcare providers are strongly associated with reporting of adverse drug reactions (ADRs). This study was conducted to evaluate knowledge, attitude, and practice toward pharmacovigilance and to identify barriers for ADR reporting among physicians working at public and private hospitals in Jordan. This study was conducted using an online questionnaire in the Arabic language, designed by the members of the Health Hazard Evaluation Committee of the Jordan Food and Drug Administration (JFDA) between (August 2016 to December 2017). The questionnaire was completed using Google Forms online. A total of 341 physicians completed the questionnaire online. The rate of reporting of ADRs is low among physicians, only 4.7% have reported an ADR. The majority of physicians had never heard the term PV before. Respondents also lacked awareness of the existence of a PV centre in Jordan, and were unaware that monitoring of ADRs is carried out by the JFDA. Although the majority of physicians had never seen the ADR form, many had positive attitudes toward reporting ADRs. According to participant responses, the main barriers to reporting are: 1) not knowing how to report, 2) not knowing the importance of reporting, 3) unavailability of the ADR form, and 4) general time pressure in the work environment. Although there is a low rate of ADR reporting among physicians, doctors have a positive attitude toward PV and are willing to implement ADR reporting in their practices. More education and training sessions are needed in order to raise physician awareness and knowledge of PV, and to enhance ADR reporting.

Effectiveness and safety of Jiuwei Zhenxin granules for treating generalized anxiety disorder: A randomized controlled trial.

BackgroundGeneralized anxiety disorder (GAD) is a chronic disorder characterized by excessive, pervasive, persistent worrying that is difficult to control. Jiuwei Zhenxin granules may be safer and more effective than non-benzodiazepine anti-anxiety drugs for treating GAD. This study aimed to assess the efficacy and safety of Jiuwei Zhenxin granules alone or in combination with the benzodiazepine alprazolam.Materials and methodsA total of 710 patients were recruited from outpatient clinics and were randomly divided into two groups to receive Jiuwei Zhenxin granules (single drug group) or Jiuwei Zhenxin granules and alprazolam (combination group). The primary outcome was the response rate, which was defined as a ≥ 50% reduction from the baseline total score on the Hamilton Anxiety Scale (HAMA). Secondary outcome measures included mean changes in HAMA total score, psychological and somatic factors, Hamilton Depression Rating Scale total score, and SF-36 health survey score.ResultsAt 4 weeks after treatment, the single and combination treatment groups showed significant improvement in the HAMA total score and they did not differ significantly in response rate (77.58 vs. 79.17%) or rate of adverse drug reactions (16.22 vs. 16.07%).ConclusionJiuwei Zhenxin granules are an effective, safe, and well-tolerated treatment against GAD. Combining them with alprazolam may not significantly improve efficacy.Clinical trial registration[www.ClinicalTrials.gov], identifier [CHICTR1800020095].

A RETROSPECTIVE STUDY: ANALYSIS OF ADVERSE DRUG REACTION IN PEDIATRIC PATIENTS IN A TERTIARY CARE HOSPITAL

Objective: The objective of this study was to analyze various parameters such as admission type, demographics, type of reaction, organ system classification, drugs involved, action is taken, reaction outcome, causality assessment, severity assessment, and the preventability of Adverse drug reactions (ADRs) in pediatric patients. Methods: This retrospective observational study was conducted during the period of September 2017 to June 2020 (34 months) at the ADR monitoring center, Department of Pharmacology, Jawaharlal Nehru Medical College, Ajmer, Rajasthan. All spontaneously reported ADRs were evaluated using various parameters such as type of reaction, causality assessment, preventability, and severity. Results: In the present study, 72 (7.27%) ADRs were reported in relation to 65 pediatric patients. In this study, more ADRs were reported in male (53.85%) as compared to female (46.15%) pediatric patients. The majority of ADRs were considered type B (63.89%), probable (87.5%), moderate (51.39%), and definitely preventable (88.89%) in nature. The majority of ADRs were reported due to antimicrobial classes of drugs, including anthelmintic drug (Albendazole), followed by glycopeptide antibiotic (Vancomycin) and third-generation cephalosporin antibiotics (Ceftriaxone, Cefotaxime, and Cefixime). The organ systems most commonly affected were skin and subcutaneous tissue disorders (47.22%), followed by general disorders and administration site conditions (20.83%) and gastrointestinal disorders (16.67%). Conclusion: The present study 30 different types of suspected ADRs that were reported with multiple frequencies, with included 34 different categories of drugs and combinations of drugs. The majority of patients recovered, with associated ADR, after necessary medical intervention and management. Our purpose is to minimize the incidence rate of ADRs in the pediatric population.

Single-center Evaluation of Safety & Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Solid Organ Transplantation.

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3-12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3-12 months post-initiation. Nadir values between 3-12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3-12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed.

A Real-world Pilot Observational Study of Neuropathic Pain Medications in Older Adult Patients in North India

Aims:This pilot study aimed to make head-to-head comparisons of multiple classes of drugs used in the management of neuropathic pain in North Indian older adult patients presenting to the geriatric clinic of a tertiary medical institutionBackground:Chronic neuropathic pain is a condition affecting nearly one third of older adults. There is paucity of data on head-to-head comparisons of drugs used in neuropathic pain in older adults. Real world studies may be a useful tool to study diverse neuropathic pain medications in this population.Objectives:The study objective was to measure NPRS (numeric pain rating scale), GDS (geriatric depression scale), IADL (instrumental activities of daily living), HMSE (Hindi mental state examination) scores at baseline, and 4- and 12-week follow-ups in all older adults patients receiving neuropathic pain medications.Methods:A prospective observational study was conducted involving older adult patients ≥ 50 years of age with painful peripheral neuropathy of any etiology (n=60; mean age 63±8.4 years). The patients received either gabapentin, pregabalin, duloxetine, amitriptyline, or methyl-cobalamin complex. NPRS, GDS, IADL, and HMSE scores were measured at baseline and post-therapy.Results:All groups except amitriptyline showed statistically significant improvement in NPRS at 4 weeks and 12 weeks compared to baseline. 30% response rate at 4 weeks was maximum for pregabalin (72%) and 50% response rate at 12 weeks was maximum for gabapentin (58%). Numerically maximum improvement in depression was seen with duloxetine. There was no statistically significant difference in the measured parameters between the drug groups across time. Mean daily dose was 172 mg (gabapentin group), 75 mg (pregabalin group) and 20 mg (duloxetine group). The adverse drug reaction rate was 10.5%.Conclusion:All drug groups showed beneficial effects on neuropathic pain at much lower doses than those described in the literature. The effectiveness at these low doses and the lower rates of adverse effects sets the foundation for larger studies in the future in diverse ethnic and aged populations.

Differences in the Recurrence Rate of Immediate Adverse Drug Reactions According to the Components of Alternative Contrast Media: Analysis of Repetitive Computed Tomography Cases in a Single Tertiary Hospital.

The recurrence rates of immediate adverse drug reactions (ADRs) to the alternative radiocontrast media (RCM) are not well known. Previous studies suggest selection of alternative RCM considering carbamoyl side chains; however, its usefulness for preventing the recurrence of ADRs has not been clearly verified. The aim of this study was to verify the recurrence rate of immediate ADRs according to the alternative RCM. This retrospective study analyzed 6420 contrast-enhanced computed tomography (CT) cases of 2009 patients registered in the ADR system from 861,664 CT cases in a single tertiary hospital between 2015 and 2020. Iohexol, iopromide, iobitridol, and iopamidol were used for CT. According to the carbamoyl side chains present, iohexol belongs to group 1, iopromide belongs to groups 1 and 2, iobitridol belongs to group 2, and iopamidol belongs to group 3. Replacing iobitridol with iopamidol (odds ratio [OR] 2.595, 95% confidence interval [CI] 1.48-4.550) or iopromide (OR 3.354, 95% CI 1.420-7.926) as the subsequent RCM was associated with increased recurrence, while replacing iopamidol with iobitridol (OR 0.506, 95% CI 0.282-0.908) and iopromide with iohexol (OR 0.355, 95% CI 0.177-0.711) was associated with decreased recurrence. Other changes did not influence the recurrence of ADRs. The recurrence of immediate ADRs increased in certain RCM combinations of preceding and subsequent CT scans, and the RCMs did not show cross-reactivity. Therefore, the clinical benefit of the alternative RCM considering cross-reactivity is limited. This result suggests that the side chains of RCM do not have an important role in the recurrence of immediate ADRs.

Correlation between Adverse Events and Antibody Titers among Healthcare Workers Vaccinated with BNT162b2 mRNA COVID-19 Vaccine.

Objectives: The BNT162b2 mRNA COVID-19 vaccine has been found to be highly effective in preventing COVID-19 but is associated with increased reactogenicity. We aimed to examine the correlation between immunogenicity and reactogenicity of the BNT162b2 vaccine. Methods: Subjects without prior SARS-CoV-2 infection that participated in active surveillance after being vaccinated with the BNT162b2 vaccine were included. Study participants reported adverse drug reactions (ADRs) through questionnaires administered by text message after receiving each dose of the vaccine. A reactogenicity score was developed based on the type and duration of ADRs. In addition, anti-receptor binding domain (RBD) levels and neutralization assays were performed 7–21 and 7–38 days after the first and second vaccine doses, respectively. Associations between ADRs and antibody levels were assessed by Spearman correlations. Multivariable logistic regression analyses were used to identify factors associated with ADRs. Results: A total of 831 health care workers were included. The mean age was 46.5 years (SD = 11.8) and 75.5% were females. 83.4% and 83.3% had at least one local ADR after the first and second doses, respectively. 33% and 83.2% had at least one systemic ADR after the first and second doses, respectively. Multivariate logistic regression analysis found a significant correlation between ADR score and anti-RBD-IgG titers (r = 0.366; p < 0.0001) after adjustment for age, gender, and days after the second vaccination. High anti-RBD-IgG levels, being younger than 55 and being female, were all correlated with increased rates of ADRs. Conclusion: BNT162b2 mRNA COVID-19 vaccine reactogenicity appears to be correlated with higher post-vaccination antibody levels and is independently associated with younger age and female gender.

Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial

IntroductionCombination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs...

Effectiveness and Safety of Rifaximin-Containing Regimens for Helicobacter pylori Eradication: Systematic Review - Are They Potential Eradication Regimens?

BackgroundRifaximin, a rifamycin antibiotic, is widely used to treat infectious diarrhea but not commonly used in H. pylori eradication. With its potential advantages of the agent, some studies were conducted on this topic. The aim of this study is to assess effectiveness and safety of rifaximin-containing regimens and to evaluate whether they are alternative choices for H. pylori eradication.MethodsScientific databases including PubMed, EMbase and Cochrane Library were used to identify clinical trials on rifaximin-containing regimens published from January 2000 to October 2021. Review Manager 5.4 and STATA12 were adopted for the systematic review.ResultsIn this study, totally 1025 patients were included from 3 randomized controlled and 9 single-arm studies. It showed that the differences in effectiveness and safety between rifaximin-containing and first-line regimens were not statistically significant in randomized controlled trials. However, the results of the single-arm trials indicated that the eradication and adverse drug reaction rate varied suggesting data instability (r=38.1%-85.4%, rADR 0.00–67.5% by ITT analysis). Among them, the eradication rate of pediatric patients (r=85.4% by ITT analysis) was higher than that of adult patients (r=38.1–74.5% by ITT analysis). Meanwhile, in all adult subgroups (triple or quadruple, with or without amoxicillin, different duration and rifaximin dose), the results did not show sufficient effectiveness as all the eradication rates did not meet the minimum ideal or ideal target.ConclusionTaken together, rifaximin-containing regimens should not be recommended for H. pylori eradication as they cannot achieve the eradication rate desired.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance.

To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy. Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi‐centre, non‐inferiority, randomized, controlled phase 3 clinical trial

Ciprofol is a propofol analogue with improved pharmacokinetic properties. A multi‐centre, non‐inferiority trial was conducted to compare the deep sedation properties of ciprofol and propofol with a non‐inferiority margin of 8% in patients undergoing gastroscopy and colonoscopy. In total, 289 patients were randomly allocated for surgery (259 colonoscopy and 30 gastroscopy) at a 1:1 ratio to be given intravenous injections of ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). The primary outcome was the success rate of colonoscopy defined as colonoscopy completion with no need for an alternative sedative or >5 ciprofol or propofol top up doses within any 15‐min time period. The success rate of colonoscopy was 100% in the ciprofol group vs. 99.2% in the propofol group (mean difference 0.8%, 95% CI: −2.2% to 4.2%). Except for the gastrointestinal lesions found during the gastroscopy and colonoscopy procedures, the occurrence rates of adverse drug reactions in the ciprofol and propofol groups were 31.3% and 62.8%, respectively (P < 0.001). Pain on injection was less common in the ciprofol group (4.9% vs. 52.4%, P < 0.001). The outcomes demonstrated that ciprofol was non‐inferior to propofol with regard to successful sedation for gastroscopy or colonoscopy procedures and no obvious important adverse events occurred.

Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

Frequency and Management of Adverse Drug Reactions Among Drug-Resistant Tuberculosis Patients: Analysis From a Prospective Study.

Drug-resistant tuberculosis (DR-TB) management is often linked with a higher rate of adverse drug reactions (ADRs) needing effective and timely management of these ADRs, which, if left untreated, may result in a higher rate of loss to follow-up of drug-resistant patients. Study objective: The study was aimed at prospectively identifying the nature, frequency, suspected drugs, and management approaches for ADRs along with risk factors of ADRs occurrence among DR-TB patients at Nishtar Medical University, Hospital, Multan, Pakistan. Materials and Methods: The prospective study included all the DR-TB patients enrolled for treatment from January 2016 to May 2017 at the study site. Patients were evaluated for the treatment-induced ADRs as per standard criteria of the National Tuberculosis Program, Pakistan. Multivariate logistic regression was used to assess the independent variables associated with the occurrence of ADRs. Results: Out of 271 DR-TB patients included in the final analysis, it was observed that 55 patients (20.3%) experienced at least three ADRs. A total of 50 (18.5%) patients experienced zero adverse effects, while 15 (5.5%), 33 (12.2%), and 53 (19.6%) patients experienced one, two, and four ADRs, respectively. Gastrointestinal disturbances (66.7%), nervous system disorders (59.4%), and electrolyte disturbances (55.7%) remained the highest reported ADRs during therapy, followed by arthralgia (49.1%), ototoxicity (24%), pruritic reactions/rash (12.9%), dyspnoea (12.5%), and tinnitus (8.8%). Pulmonary cavitation at the baseline visit (p-value 0.001, OR 3.419; 95% CI (1.694–6.902) was significantly associated with the occurrence of ADRs among DR-TB patients. Conclusion: The frequency of ADRs was high among the study cohort; however, these were managed effectively. Patients with recognized risk factors for ADRs occurrence need continuous clinical management efforts.

A real-world, non-interventional, prospective study of the effectiveness and safety of apremilast in bio-naïve adults with moderate plaque psoriasis treated in the routine care in Greece - the 'APRAISAL' study.

Real-world data in patients with moderate psoriasis treated with apremilast is limited. To evaluate the effectiveness and safety of apremilast in bio-naïve patients with moderate psoriasis in real-world clinical settings. This was a 52-week multicenter, observational, prospective study of adult outpatients with moderate psoriasis {[10% < body surface area < 20% or 10 < psoriasis area severity index (PASI) < 20] and 10 < dermatology quality of life index (DLQI) < 20} initiated on apremilast ≤7 days before enrollment. Missing data were imputed using the last observation carried forward method. A total of 287 eligible patients (median age: 54.2 years; median psoriasis duration: 9.8 years) were consecutively enrolled. At baseline, the median DLQI and PASI scores were 12.0 and 11.8, respectively. The 52-week DLQI ≤ 5 and PASI75 response rates were 68.3% and 61.0%. At 52 weeks, 70.8% and 72.7% of the patients shifted from moderate/severe/very severe to clear/minimal scalp and palmoplantar psoriasis involvement, respectively; the pruritus severity state improved in 67.2%. The 52-week Kaplan-Meier estimated drug continuation rate was 85.3%. The adverse drug reaction rate was 19.9%. Apremilast is a safe and effective treatment for bio-naïve patients with moderate psoriasis and specific psoriasis manifestations.

Interim results from a postmarketing surveillance study of patients with FLT3-mutated relapsed/refractory AML treated with the FLT3 inhibitor gilteritinib in Japan.

ObjectiveGilteritinib received approval for the treatment of FLT3-mutated relapsed or refractory acute myeloid leukemia in Japan in 2018. In accordance with regulatory requirements, we conducted a multicenter, observational surveillance of gilteritinib use in Japan.MethodsPatients were followed for 6 months from gilteritinib treatment initiation. The primary endpoint of the surveillance was incidence of adverse drug reactions related to each element of the safety specification defined in the Japanese Risk Management Plan. This interim analysis presents data collected from 3 December 2018 to 20 September 2020.ResultsAmong 204 patients with case report forms, 107 consented to data publication. Of these 107 patients, 59.8% (n = 64) were male and 58.9% (n = 63) were aged ≥65 years; most received a 120-mg/day initial (80.4%; 86/107) and maximum (74.8%; 80/107) daily dose. The discontinuation rate was 61.7% (66/107); the most common reasons for discontinuation were disease progression (18.7%), transplantation (16.8%) and adverse events (15.0%). The adverse drug reaction rate was 77.6%. The incidences of adverse drug reactions (grade ≥ 3) related to each element of the safety specification were myelosuppression, 44.9% (38.3%); liver function disorder, 24.3% (6.5%); infections, 24.3% (21.5%); prolonged QT interval, 10.3% (2.8%); hemorrhage, 9.3% (6.5%); renal dysfunction, 6.5% (0); hypersensitivity, 5.6% (1.9%); interstitial lung disease, 4.7% (3.7%); cardiac failure/pericarditis/pericardial effusion, 1.9% (0.9%); pancreatitis, 0.9% (0); posterior reversible encephalopathy syndrome, 0.9% (0.9%). The composite complete remission rate was 62.7%; the 6-month overall survival rate was 77.7%.ConclusionGilteritinib treatment for 6 months in Japan was associated with acceptable efficacy and no new safety concerns were observed.