Administration Site Conditions Research Articles

Analysis of Docetaxel Adverse Drug Reactions: A Retrospective Study Based on Iraqi Pharmacovigilance Center Database

Docetaxel is an effective treatment approved for many types of cancers, but its effectiveness in clinical practice can be compromised by significant occurrence of adverse drug reactions. The aim of the current study was to measure the distribution of adverse drug reactions of docetaxel reported in Iraq and to assess the causality, severity, seriousness, preventability, expectedness and outcome of these adverse reactions. A retrospective study conducted on individual case safety reports from the Iraqi Pharmacovigilance Center / Ministry of Health. The study included 118 individual case safety report containing 236 adverse drug reactions.Most of the adverse drug reactions were related to skin and subcutaneous tissue disorders(26.7%), followed by respiratory, thoracic and mediastinal disorders (20.8%), gastrointestinal disorders (17.4%) and general disorders and administration site conditions (10.6%). The majority of these reactions with possible causality (68.6%), moderate severity (75.4%), expected (80.5%), possibly preventable (93.2%), and serious (80.5%). In addition the most common outcome of adverse drug reactions was recovered / resolved (46.19%).

Adverse drug reactions in elderly: a five-year review of spontaneous reports to the Portuguese pharmacovigilance system

ABSTRACT Background: Adverse drug reactions (ADRs) are responsible for considerable morbidity and mortality in elderly. This study aimed to characterize the ADRs profile in Portuguese elderly patients, thus enhancing ADRs knowledge in this vulnerable population. Methods: All spontaneous ADRs reported to the Portuguese Pharmacovigilance System from 2013 to 2017 were examined. However, considering the aim of this study, ADRs referring to patients aged 65 and over were analyzed in higher detail and compared with those reported in non-elderly adults. Results: Considering the age of 65 years and above, 3692 spontaneous reports of suspected ADRs were analyzed. The suspected ADRs most frequently reported fall within the categories of general disorders and administration site conditions, and skin and subcutaneous tissue complaints. Regarding therapeutic agents, the antineoplastic drugs were the most common involved. Among the 2458 cases of serious ADRs reported, 34.0% led to hospitalization and in 5.8% of them occurred a fatal outcome. The antineoplastic and antithrombotic drugs were the most represented pharmacotherapeutic groups of suspected drugs involved in patient’s death (25.0% and 13.6%, respectively). Conclusions: Most of the suspected ADRs were classified as serious. The majority of them were expected, so preventable, highlighting the importance of improving medication use in elderly.

Red yeast rice (Monascus purpureus) supplements: Case series assessment of spontaneously reported cases to The Netherlands Pharmacovigilance Centre Lareb.

Serious concerns are expressed on the safe use of red yeast rice (RYR) supplements. The aim of the present study was to analyse cases received by Lareb on RYR‐related adverse health events. These cases were analysed for the number of reports, number of adverse drug reactions (ADRs), causality, seriousness of the reaction, latency‐period, age and sex of the patients, concomitant medication and type of reporter. A total of 94 individual reports were collected by Lareb, corresponding with 187 ADRs. The analysis showed most reported ADRs were labelled musculoskeletal and connective tissue disorders (n = 64), gastrointestinal disorders (n = 33) and general disorders and administration site conditions (n = 23). The use of RYR supplements should be considered as a significant safety concern. Exposure to monacolin K could lead to serious adverse effects. To fully assess the safety profile of RYR supplements, more research is necessary to compose a complete ADR profile of RYR supplements.

Phase II Single-Arm “Window-of-Opportunity” Study of a Combination of Obinutuzumab and Venetoclax in Early Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) - First Results of the AGMT NHL15B Study

Phase II Single-Arm “Window-of-Opportunity” Study of a Combination of Obinutuzumab and Venetoclax in Early Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) - First Results of the AGMT NHL15B Study

Effect of Age on the Efficacy and Safety of Single Agent Oral Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL): A Post-Hoc Analysis of the Sadal Pivotal Study

Effect of Age on the Efficacy and Safety of Single Agent Oral Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL): A Post-Hoc Analysis of the Sadal Pivotal Study

Patient-Reported Adverse Events of Radiopharmaceuticals: A Prospective Study of 1002 Patients.

IntroductionAdverse events of radiopharmaceuticals may be underreported or remain undetected. Patients can provide information about these adverse events to enable healthcare professionals to detect, understand, and manage them more efficiently.ObjectiveIn this study, we aimed to (a) determine the type, causality, and frequency of patient-reported adverse events of radiopharmaceuticals and to (b) assess the onset, outcome, and follow-up of these adverse events from the patient’s perspective.MethodsWe performed a prospective cohort study of 1002 patients who underwent a nuclear medicine examination. Using a validated questionnaire, we collected patient-reported information on adverse events that occurred immediately after administration of the radiopharmaceutical as well as those that occurred later. Adverse events were analysed, coded and assessed for causality by two independent researchers.ResultsA total of 187 (18.7%) patients reported 379 adverse events. Most patient-reported adverse events of radiopharmaceuticals belonged to the ‘general disorder and administration site conditions’ (42.0%) and ‘nervous system disorders’ (16.9%) system organ classes. Of the patient-reported adverse events, 43.0% were possibly or probably causally related to radiopharmaceuticals. We found the frequency of patient-reported adverse drug reactions to diagnostic radiopharmaceuticals to be 2.8%. No important medical events were related to the administrations of diagnostic radiopharmaceuticals. Most adverse events (80.0%) occurred shortly after administration of the radiopharmaceutical and were resolved within a few hours. Some events (20.0%) emerged after patients had left the nuclear medicine department, took longer to resolve, and sometimes prompted the patient to consult a healthcare professional.ConclusionAdverse reactions to diagnostic radiopharmaceuticals can occur, and the frequency reported by patients was found to be 2.8%, which is higher than reported in the existing literature. We hope that the results of this study increase awareness of these adverse reactions among patients and healthcare professionals.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-01006-2) contains supplementary material, which is available to authorized users.

Reporting of Safety Events during Anti-VEGF Treatment: Pharmacovigilance in a Noninterventional Trial.

Aim The prospective, noninterventional OCEAN study assessed the safety of intravitreal ranibizumab injections for treatment of neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion under real-world conditions in Germany. Methods Adults receiving ≥1 ranibizumab (0.5 mg) injections were recruited by 369 ophthalmologists and followed for 24 months. Information on adverse events (AEs) was reported by the treating physician or detected by the data management team. Collected information included observed AE, AE start and end date, intensity, causal relationship, outcome, severity, suspected drug, and actions taken. Results 2,687 AEs were reported for 1,176 of the 5,781 patients who had received a total of 32,621 injections: 27.4% nonserious AEs, 30.3% serious AEs, 27.3% nonserious adverse drug reactions (ADRs), and 15.0% serious ADRs. Most patients reported no AEs (79.7%) or only 1 AE (10.3%). AEs were most commonly reported in the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) Eye disorders (9.4% of patients) and General disorders and administration site conditions (5.8%). The most frequent AEs by MedDRA preferred term (PT) were visual acuity reduced (3.5% of patients), intraocular pressure increased (2.5%), and drug ineffective (2.1%). AEs occurred most frequently after 3 or 4 injections (1,129 of 2,687 AEs). The proportion of AEs in the SOC Eye disorders decreased slightly with increasing number of injections, from 39.8% of events after 1 or 2 injections to 29.1% after 5 or more injections. Rates of the most frequently reported PTs did not show any consistent increase with increasing number of injections. A decrease in overall AE rates was observed over the study course. Conclusions The results did not raise any new safety concerns for ranibizumab. The findings allow conclusions to be drawn on how pharmacovigilance data can be collected even more effectively in real-world studies to facilitate discussion on benefit-risk ratio.

Abstract 4227: Safety of dendtritic cell and cytokine-induced killer(DC-CIK) cell based immunotherapy in patients with solid tumor: A large retrospective study in China

Abstract Background: Adoptive T cell therapy especially cytokine-induced killer cell and dendric cell treatment (DC-CIK) alone or combined with chemotherapy had significantly improved patient survival time. Although some side effects studies were briefly reported in some articles. However, systematic assessment of the adverse side effects for DC-CIK therapy, especially combined with chemotherapy has not been reported. Patients and Methods: Totally 1099 consecutive patients (2054 trail cycles) enrolled in DC-CIK treatment trials at Beijing Shijitian hospital between August 2012 and August 2018 were retrospectively reviewed, and applying Common Terminology Criteria for Adverse Events version 4.0 [CTCAE v4.0] standards to definite adverse effects (AE). Result: The 370 patients (34%)/ 815 cycles enrolled in our trail combined with chemotherapy. In total, there were 548(cases)/870(cycles) had AEs. The AE class mainly composed of Neurological 34 cycles (4%), Musculoskeletal 28 cycles (3%), Immunopathies 5 cycles(1%), Hematological 521 cycles(60%), General disorders and Administration site conditions 224 cycles(26%), Gastrointestinal 209 cycles(24%), Skin 15 cycles(2%), Metabolism and Nutrition disorders 119 cycles(14%). AE class of the Gastrointestinal (vomiting P=0.025), Nutrition disorders (anorexia P=0.016) and Hematological (anemia P<0.0001, leukopenia P<0.0001) appears in the DC-CIK treatment were mainly correlated with combined with chemotherapy. Multiple logistic regression analysis suggests that no matter whether DC-CIK was combined with chemotherapy, multi-line treatment was more prone to nausea, anorexia, fatigue, anemia and leukopenia than the first-line treatment. However, correlation analysis verified that increasing cycles of only DC-CIK treatment could reduce the incidence rate of fatigue (P=0.001), anorexia (P<0.0001) and anxiety (P=0.01). Conclusion: Most of the adverse side effects that occur during autologous DC-CIK treatment were associated with combined or previously applied chemotherapeutic treatment, which also indicates that autologous DC-CIK anti-tumor therapy was safe. At the same time, the application of DC-CIK alone treatment could also reduce the occurrence rate of some side effects. Citation Format: Shuo Wang, Jun Ren. Safety of dendtritic cell and cytokine-induced killer(DC-CIK) cell based immunotherapy in patients with solid tumor: A large retrospective study in China [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4227.

A 7-Years Active Pharmacovigilance Study of Adverse Drug Reactions Causing Children Admission to a Pediatric Emergency Department in Sicily.

Children represent one of the most susceptible groups to adverse drug reactions (ADRs), as a consequence of physiological growth and maturation of different organ systems. The aim of this study was to characterize the frequency, preventability and seriousness of ADRs recorded in the Pediatric Emergency Department (ED) of the University hospital of Messina, in Sicily. All the suspected adverse reactions to drugs and vaccines collected from 2012 to 2018 were selected and then analyzed. Only adverse drug reactions (ADRs) with a probable or possible causality assessment were included, according to the Naranjo Algorithm and the World Health Organization criteria; the preventability assessment using Schumock and Thornton criteria was also carried out. The Medical Dictionary for Regulatory Activities (MedDRA) was used to group ADRs. Of 75,935 admissions to the Pediatric ED, 120 were due to suspected ADRs. The rate of hospital admission due to ADRs (75.8%) was significantly greater than that of patients without ADRs (11.9%). Among pediatric patients with ADRs the median (Q1–Q3) age was 29.5 (12–73.25) months. Most of ADRs were observed in infants and children (43.3% and 41.7%, respectively vs adolescents, 15%). In addition, in children with ADRs, females [41 (14–105)] were older than males [23 (11–45)] (p=0.044). Most adverse reactions were serious (75.8%) and 20.8% were preventable or probably preventable; however, the majority of serious ADRs (93.4%) resulted without sequelae. The reactions were found to be as probable (54.2%) or possible (45.8%). Vaccines (n=63), antibacterials (n=31) and anti-inflammatory medicines (n=14) were the most frequently drugs involved. Organ toxicity mapping due to vaccines was general disorders and administration site conditions (65.1%), nervous disorders (50.2%), cutaneous disorders (35%), followed by gastrointestinal disorders (20.6%). Cutaneous disorders (76%) gastrointestinal (20.7%), general (15.5%), and nervous disorders (8.6%) were the organ toxicity mapping due to drugs. Active pharmacovigilance has an essential role in supporting the development of strategies aimed at intervention to reduce admissions due to ADRs. Our data suggest that ADRs represent the first cause of hospitalization to the Pediatric Emergency Department. Furthermore, according to the literature, vaccines and antibiotics are the most frequent cause of adverse drug reactions in children.

Adverse drug reactions in adolescents: a review of reporting to a national pharmacovigilance system

ABSTRACT Objective Adverse drug reactions (ADR) cause significant morbidity, mortality and health costs and have an important prevalence in all ages. Few studies focus on ADR in adolescents. The goal of this study was to characterize a case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) of the National Authority of Medicines and Health Products (INFARMED, I.P.) during an eleven-year period (from 2006 to 2016) concerning this specific population. Methods Retrospective analysis of reports concerning patients from 10 to 18 years received by the PPS between 2006 and 2016. The authors evaluated patients’ demographics (age and sex). The characteristics and seriousness of the reactions, the type of reaction reported, and the drugs involved were assessed. Results The authors found 782 reports (59% females). Most reports came from physicians (61%). Overall 80% of the reports described serious ADR. A greater proportion of serious events was found among males. Most reactions referred to general disorders and administration site conditions (38%), followed by skin and subcutaneous tissue reactions (33%). In 3rd and 4th were gastrointestinal disorders (24%) and the nervous system disorders (23%), the former more frequent among females. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (19%). Conclusion Major findings considering drugs involved and the reported reactions varied according to age and sex.

Biosimilar trastuzumab active post-marketing surveillance real-world data update: Results from a patient support program for patients under treatment with the first biosimilar trastuzumab approved in Brazil.

e15626 Background: In 2017, biosimilar trastuzumab (Zedora) became the first biosimilar trastuzumab approved in Brazil. In 2019, biosimilar trastuzumab early data from an active postmarketing surveillance program were presented in ASCO. Now, with an extended follow up and more patients included, we present updated data from the surveillance program. Methods: This is a prospective observational study based on a patient support program. HER2 + breast cancer (BC) who received prescription for biosimilar trastuzumab were invited to participate. After agreement of informed consent, they were followed by periodical phone calls after each infusion and up to 3 months after the end of treatment. Treatment related data and adverse events (AEs) were collected. Results: A total of 76 female patients with HER2 + BC were enrolled in the program between May 2018 and December 2019. 74 patients with median age 51 (range 30 to 80) received at least one biosimilar trastuzumab infusion. Out of these, 52 (70.3%) patients reported 385 AEs all-causality (Table 1). Regarding severity and expectedness, 344 (89.4%) were non-serious AE (243 expected / 101 unexpected) and 41 (10.6%) were serious AE (29 expected / 12 unexpected). Considering all serious unexpected AEs (12), 8 were assessed as unlikely and 4 as likely. For the non-serious unexpected AEs (101) causality assessment was unlikely in 32 AEs, likely in 68 AEs and conditional in 1 AE. The three most frequently reported AEs according to SOC (System Organ Classification) were gastrointestinal disorders 59 (15.3%), general disorders and administration site conditions 57 (14.8%). The five most reported symptoms (PT - Preferential Term) were nausea 15 (3.9%), fatigue 14 (3.6%), infusion reactions 14 (3.6%), diarrhea 9 (2.3%) and insomnia 9 (2.3%). Further monitoring is continued. Conclusions: Nature of AEs for biosimilar trastuzumab are consistent with the label in female patients with HER2 + BC. The risk benefit remains consistent with the label and no new safety signals were detected. [Table: see text]

National Cross-Sectional Study of Community-Based Adverse Drug Reactions in Saudi Arabia

BackgroundAn adverse drug reaction (ADR) is a response to a medicine that is not intended and is harmful, and which occurs at normal dose levels for humans. Currently, there are no estimates of the population-based prevalence of ADRs in the Kingdom of Saudi Arabia (KSA).ObjectiveThe aims of this study were to (1) estimate the population-based prevalence of ADRs in KSA, (2) describe the ADRs experienced by survey respondents, and (3) investigate the level of awareness of the ADR reporting system.Patients and MethodsThis was a cross-sectional survey using stratified, population-based sampling conducted at a chain of community pharmacies.ResultsAnalysis was conducted on 5228 surveys; 50.17% of respondents were males, and the mean age was 39 ± 15 years (min = 18, max = 98). The sample prevalence of ADRs was 23.45% (95% CI 22.30–24.60%, P < 0.001). The estimated population prevalence (after weighting) was 28.00% (26.10–30.00%). Gastrointestinal disorders were the most commonly reported ADRs (58.73%), followed by general disorders and administration site conditions (19.74%). The largest drug class that was reported to lead to ADRs was nonsteroidal anti-inflammatory drugs (NSAIDs) (11%). Over 19% of the respondents who experienced an ADR required medical intervention to control the suffering induced by the ADR. Of the respondents who experienced an ADR, 371 (30.26%) were aware of the ADR reporting system but only 53 (14.29%) said that they had filed a report in the system.ConclusionsOur study estimated that 28% of the population experienced an ADR over a 1-year period in KSA. Risk factors for ADR included certain chronic disease groups and the use of certain classes of medications. Regulatory authorities in KSA intend to conduct more research and deploy educational interventions to reduce ADR rates in KSA. This will hopefully occur in an international context that promotes the standardized measurement of ADRs in the community. A subset of findings from this report was presented in an oral presentation at the Saudi Food and Drug Authority (SFDA) Annual Conference, September 27, 2018. In addition, a subset of findings from this report were presented on a poster at the International Conference of Pharmacoepidemiology and Therapeutic Risk Management (ICPE), August 27, 2019.Electronic supplementary materialThe online version of this article (10.1007/s40801-020-00186-8) contains supplementary material, which is available to authorized users.

Adverse event reports in patients taking psychiatric medication during pregnancy from spontaneous reports in Japan and the United States: an approach using latent class analysis

BackgroundLittle is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US).MethodsWe summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications.ResultsThe proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8).ConclusionsThe main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

Assessment of Causality, Severity and Seriousness of Adverse Event Following Immunization in Iraq: A Retrospective Study Based on Iraqi

Immunization is one of the most cost-effective and successful public health applications. The results of immunization are difficult to see as the incidence of disease occurrence is low while adverse effects following the immunization are noticeable, particularly if the vaccine was given to apparently healthy person. High safety expectations of population regarding the vaccines so they are more prone to hesitancy regarding presence of even small risk of adverse events which may lead to loss of public trust to the vaccination programs.&#x0D; Vaccine safety monitoring is needed as they now are administered to the general population and also available to special categories such as pregnant women and patients with different diseases whom not subjected to clinical trials as well as incorrect administration rout and presence of rare or delayed onset adverse events make the presence of surveillance system necessary. The aim of the current study was to measure the distribution, percentage, and frequency of adverse reactions related to vaccines administration in Iraq and to assess the causality, severity, seriousness of these adverse reactions. This study is a retrospective descriptive study for surveillance of vaccine safety conducted using Iraqi pharmacovigilance center database from 2014 till the end of 2018 . 2116 Adverse events were included and outcomes , severity , seriousness , and causality of adverse events were assessed. Majority of adverse events following immunization cases (90.97%) were mild, non serious (94.47%) and recovered (94.23%). Most reports were for general disorders and administration site conditions and the majority were for elevated body temperature and injection site reactions .

Phase III Clinical Trial of Elizaria® and Soliris® in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria: Results of Comparative Analysis of Efficacy, Safety, and Pharmacological Data

Introduction: Complement C5-inhibitor eculizumab is a current standard of care in patients with paroxysmal nocturnal hemoglobinuria (PNH). Elizaria® is the first registered biosimilar of the reference medicinal product Soliris®. Purpose: To demonstrate Elizaria® comparative efficacy and safety vs. reference product Soliris® in patients with paroxysmal nocturnal hemoglobinuria. Methods: 32 patients with PNH were stratified based on the previous eculizumab treatment status (eculizumab-naive patients/patients treated with eculizumab at a maintenance regimen before enrollment) and randomized to receive Elizaria® (n = 16) or Soliris® (n = 16). Eculizumab-naive patients with baseline LDH level ≥1.5 times the upper limit of normal started induction phase of four weekly infusion of the study medications at dose of 600 mg, with subsequent maintenance therapy at dose of 900 mg every two weeks. Previously treated patients started the study treatment at the maintenance dose. The total treatment duration was 26 weeks. Comparative evaluation of chronic hemolysis based on the area under the curve "LDH concentration-time" (LDH AUC) during the maintenance therapy period was the primary endpoint of the study. The main secondary efficacy parameters were hemoglobin dynamics, breakthrough hemolysis and transfusion dependence. PK profile as well as through eculizumab and membrane attack complex (MAC) concentration were also assessed during the treatment. Results: Thirty patients have completed the study without significant protocol deviations (16 patients in Elizaria® group and 14 patients in Soliris® group). The LDH AUC was highly variable between the patients but the means were not statistically differ between the treatment groups: 62,957.6 ± 46,066.5 U/L*day (95% CI [38,410.4; 87,504.7]) and 49,702.6 ± 26,182.1 U/L*day (95% CI [34,585.5; 64,819.7]) in Elizaria® and Soliris® groups respectively. Point estimation of the intergroup difference in LDH AUC of 13255,0 U/L*days (95% CI [-10492,9; 37002,8]) comprises 12,3% of the pre-specified non-inferiority margin of 150,635 U/L*days, that is not supposed clinically significant difference (Figure 1). The treatment groups were also comparable on all the secondary efficacy parameters (Table 1). The comparative PK parameters of eculizumab and MAC concentration have been demonstrated in the treatment groups in all studied time points. Thus, the median elimination half-life (T1/2) of eculizumab amounted to 187,7 h (IQR 165,7) in Elizaria® group and to 282,0 h (IQR 152,3) in Soliris® group (p = 0.236). The minimum concentration (Cmin) of eculizumab amounted to (64.89 ± 25.96) µg/mL in Elizaria® group and to (94.13 ± 58.76) µg/mL in Soliris® group (p = 0.065). The median residence time (MRT) of eculizumab amounted to 269,5 h (IQR 257.3) in Elizaria® group and to 393,1 h (IQR 240,9) in Soliris® group (p = 0.206). By the end of the study, the mean MAC values one hour after the study products infusion amounted to (170.41 ± 72.21) ng/mL and (214.08 ± 93.57) ng/mL in Elizaria® and Soliris® groups, respectively (Figure 2). Both Elizaria® and Soliris® demonstrated the similar safety profile. Thirteen adverse drug reactions (ADR) in 5 patients were reported in the study: 9 - in 3 Elizaria® patients, whereas 4 were reported in 2 Soliris® patients. ADRs were observed in the following system organ classes: Investigations (9.4%), Blood and lymphatic system disorders (6.3%), Infections and infestations (6.3%), Renal and urinary disorders (3.1%), General disorders and administration site conditions (3.1%), Metabolism and nutrition disorders (3.1%). No new cases of anti-drug antibody formation have been revealed during the study. Conclusion: Thus, the results of the clinical trial confirm that proposed biosimilar Elizaria® is comparable to the reference product Soliris® in term of efficacy, safety, immunogenicity and PK/PD parameters in the treatment of paroxysmal nocturnal hemoglobinuria. Disclosures Kulagin: Alexion Pharmaceuticals, Inc:: Consultancy, Honoraria; JSC GENERIUM: Consultancy, Honoraria, Research Funding. Ptushkin:Alexion Pharmaceuticals, Inc:: Consultancy, Research Funding; JSC GENERIUM: Research Funding; Janssen: Consultancy; AbbVie: Consultancy; Roche: Consultancy. Lukina:JSC GENERIUM: Research Funding; Sanofi Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Reimbursement, Research Funding; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Reimbursement. Gapchenko:JSC GENERIUM: Employment. Markova:JSC GENERIUM: Employment. Zuev:JSC GENERIUM: Employment. Kudlay:JSC GENERIUM: Employment.

Biological therapy-associated adverse reactions in asthma: analysis of reporting to the Portuguese pharmacovigilance system

ABSTRACT Objectives: Biological drugs have been successfully tested in asthma, especially in the most severe forms of the disease. The goal of this study was to characterize the safety profile of biologicals used in asthma. Methods: Retrospective and descriptive analysis of spontaneous reports (SRs) involving omalizumab and mepolizumab, sent to the Portuguese Pharmacovigilance System, since market launch until October 2018. Results: A total of 127 SRs for omalizumab and 10 SRs mepolizumab were found. Most patients were female (75.6% omalizumab and 90.0% mepolizumab), and aged 18–64 years (61.4% and 50.0%, respectively). 71.7% of the reports for omalizumab were serious, with 2 cases of anaphylaxis, 12 malignant neoplasms and 2 abortions. Only 20.0% of the reports for mepolizumab were considered serious. A total of 391 adverse drug reactions (ADRs) for omalizumab and 20 ADRs for mepolizumab were found. Most reported ADRs belonged to System organ class (SOC) groups: ‘respiratory, thoracic and mediastinal disorders’ and ‘investigations’, for omalizumab; ‘musculoskeletal and connective tissue disorders’ and ‘general disorders and administration site conditions’ for mepolizumab. Conclusion: Over the years, there was an increasing trend of SRs with these biological drugs. However, it is necessary to continue to develop educational programs in order to get a better reporting system.

Investigating safety profiles of human papillomavirus vaccine across group differences using VAERS data and MedDRA.

BackgroundThe safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. This study aimed to evaluate the safety profiles of human papillomavirus (HPV) vaccines with regard to the distribution of adverse events (AE) across gender and age, and the correlations across various AEs using the Food and Drug Administration/Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System (VAERS).MethodsFor analyses, 27,348 patients aged between 9 and 25 years old with at least one AE reported in VAERS between the year of 2006 and 2017 were included. AEs were summarized into two levels: the lower level preferred term (PT) and higher level system organ classes (SOCs) based on the structure of Medical Dictionary for Regulatory Activities (MedDRA). A series of statistical analyses were applied on both levels of AEs. Zero-truncated Poisson regression and multivariate logistic regression models were first developed to assess the rate and risk of SOCs across age groups and genders. Pairwise Pearson correlation analyses and hierarchical clustering analyses were then conducted to explore the interrelationships and clustering pattern among AEs.ResultsWe identified 27,337 unique HPV vaccine reports between 2006 and 2017. Disproportional reporting of AEs was observed across age and gender in 21 SOCs (p < 0.05). The correlation analyses found most SOCs demonstrate weak positive correlations except for five pairs which were negatively correlated: skin and subcutaneous tissue disorders + injury poisoning and procedural complications; skin and subcutaneous tissue disorders + nervous system disorders; Skin and subcutaneous tissue disorders + pregnancy, puerperium and perinatal conditions; nervous system disorders + pregnancy, puerperium and perinatal conditions; pregnancy, puerperium and perinatal conditions + general disorders and administration site conditions. Nervous system disorders had the most AEs which contributed to 12,448 (46%) cases. In the further analyses of correlations between PT in nervous system disorders, the three most strongly correlated AEs were psychiatric disorders (r = 0.35), gastrointestinal disorders (r = 0.215), and musculoskeletal and connective tissue disorders (r = 0.261). We observed an inter-SOCs correlation of the PTs among AE pairs by nervous system disorders/psychiatric disorders/gastrointestinal disorders/musculoskeletal and connective tissue disorders.ConclusionsThe analyses revealed a different distribution pattern of AEs across gender and age subgroups in 21 SOC level AEs. Correlation analyses and hierarchical clustering analyses further revealed several correlated patterns across various AEs. However, findings from this study should be interpreted with caution. Further clinical studies are needed to understand the heterogeneity of AEs reporting across subgroups and the biological pathways among the statistically correlated AEs.

Interferon Beta: Analysis of Information on Adverse Reactions and Evaluation of Possibility of Signal Identification

Multiple sclerosis is one of the most common neurological diseases of working age population. The last 20 years widely use drugs that change the course of multiple sclerosis. The article is devoted to the problems of the safety of treatment of multiple sclerosis with interferon beta drugs. The aim of the study was to analyze the adverse drug reactions (ADRs) of interferon beta medicines and the assessment of the possibility of identify signals on rare adverse drug reactions based on spontaneous reporting data. A retrospective analysis of reports of ADRs that occur after the use of interferon beta-1a, interferon beta-1b was performed. The results confirm the known risks of developing ADRs of this group of drugs: general disorders and administration site conditions, nervous system disorders, musculoskeletal and connective tissue disorders and psychiatric disorders. Under-reporting of ADR was identified, high level reporting rate from manufacturers was detected. A significant number of received spontaneous reports contained information about serious ADRs (52.9 % — for interferon beta-1a; 29.4 % — for interferon beta-1b). All ADRs corresponded to those specified in the instructions for medical use of drugs. The results of the study confirmed the possibility of identifying signals associated with the occurrence of very common, common, and uncommon ADRs, such as thrombocytopenia.

PF411 ENESTOP 192‐WK RESULTS: DURABILITY AND IMPACT ON QUALITY OF LIFE OF TREATMENT‐FREE REMISSION (TFR) FOLLOWING SECOND‐LINE (2L) NILOTINIB (NIL) IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA (CML)

Background:The ENESTop study (NCT01698905) is evaluating TFR in pts with CML in chronic phase who achieved sustained deep molecular response with 2L NIL. In the primary analysis, 57.9% of pts remained in TFR 48 wks after stopping NIL. Analyses at 144 wks showed durability of TFR.Aims:To assess the maintenance and safety of TFR after a longer follow‐up of 192 wks.Methods:Eligible pts had received ≥3 y of treatment (including &gt;4 wks of imatinib followed by ≥2 y of NIL) and had achieved MR4.5 (BCR‐ABL1 IS ≤0.0032%) on NIL. Pts without confirmed loss of MR4.5 after 1 y of consolidation (CONS) treatment could attempt TFR. NIL was resumed upon loss of major molecular response (BCR‐ABL1 IS ≤0.1%) or confirmed loss of MR4 (BCR‐ABL1 IS ≤0.01%). By the data cut‐off (24 Sep 2018), all pts had either completed ≥192 wks of TFR, resumed NIL, or discontinued the study.Results:At the data cut‐off, of the 126 pts who entered TFR, 56 remained in TFR, 59 had resumed NIL and 11 had discontinued the study. At 192 wks, the TFR rate was 46.0% (58/126; 95% CI, 37.1–55.1%); all but 1 pt were in MR4.5. Of pts in TFR at 144 wks, only 1/61 had lost response (confirmed loss of MR4) by 192 wks; 2 other pts had discontinued due to pt/guardian decision and serious AE (polycythemia vera), respectively. Of pts who resumed NIL, 56/59 (94.9%) and 55/59 (93.2%) regained MR4 and MR4.5, respectively. Of 56 pts who regained MR4, 40 (71.4%) had stable MR4 96 wks later; the remaining 16 had either discontinued &lt;96 wks after regaining MR4 (n = 12) or were ongoing with &lt;96 wks after regaining MR4 (n = 4). Of 55 pts who regained MR4.5, 37 (67.3%) had stable MR4.5 96 wks later; the remaining 18 pts had either discontinued &lt;96 wks after regaining MR4.5 (n = 12) or were ongoing with &lt;96 wks after regaining MR4.5 (n = 6). There were no cases of disease progression or deaths due to CML. No new deaths have occurred since the 144‐wk analysis. The treatment‐free survival rate at 192 wks was 50.3% (95% CI, 41.2–58.7%; Figure). During CONS and the 1st, 2nd, 3rd and 4th 48‐wk periods of TFR, respectively, rates of all‐grade AEs were 80.6%, 85.5%, 67.7%, 51.6% and 56.5% among the 62 pts who remained in TFR for &gt;144 wks. Musculoskeletal pain AE rates increased during the first 48 wks of TFR (53.2%) vs CONS (11.3%), then decreased during each subsequent 48‐wk period of TFR to levels below that seen in CONS (21.0%, 14.5% and 3.2%, respectively). In pts who resumed NIL (n = 59), the most common AEs were hypertension (20.3%) and arthralgia (13.6%), with the majority of AEs being grade 1/2. The rates of frequently occurring (&gt;10% on treatment) additional AEs (grouped by category) that may affect quality of life were assessed during CONS and the subsequent 48‐wk periods of TFR to further explore the potential impact of TFR. During these study periods, respectively, incidences of these categories of AEs were: gastrointestinal disorders, 22.6%, 17.7%, 21.0%, 8.1% and 8.1%; infections and infestations, 35.5%, 37.1%, 21.0%, 17.7% and 16.1%; musculoskeletal and connective tissue disorders: 24.2%, 62.9%, 29.0%, 22.6% and 12.9%; general disorders and administration site conditions (eg, asthenia, pyrexia): 11.3%, 21.0%, 4.8%, 4.8% and 6.5%. Across these AE categories, incidences tended to decrease over time in TFR.Summary/Conclusion:These results demonstrate the long‐term durability and safety of TFR following 2L NIL. No disease progressions or CML‐related deaths were reported. Musculoskeletal pain AEs were transient and additional AEs that may impact quality of life tended to decrease in frequency during TFR.image

Adverse drug reactions of antineoplastic and immunomodulating agents reported to the Egyptian Pharmaceutical Vigilance Center

The aim of this study was to evaluate the pattern of Adverse Drug Reactions (ADRs) related to antineoplastic and immunomodulating agents in Egypt. We extracted all ADR reports of antineoplastic and immunomodulating agents (Anatomical Therapeutic Chemical (ATC) code L) that were reported to Egyptian Pharmaceutical Vigilance Center (EPVC) from January 2011 to December 2015 using VigiLyze TM. Afterwards, these reports were analyzed and categorized by age, sex, reporter qualification, seriousness, type of ADRs, medications, indications of use and causality. During the study period, 1905 reports related to antineoplastic and immunomodulating agents were received; 44.6% of which were reported by consumers and 56.8% by health care professionals. ADRs were serious in 13.3% and 65.1% of the cases reported by consumers and healthcare professionals, respectively. Approximately half (52.5%) of the reported ADRs occurred in females and only 8.4% occurred in children. Half of the reported ADRs ( 51.5%) occurred in middle aged group (45- 64 years). The most reported classes at the therapeutic level were immunostimulants (ATC code L03) and antineoplastic agents (ATC code L01). The most frequently reported medication was peg-interferon alfa-2a. The majority of ADRs were of the type general disorders and administration site conditions and gastrointestinal disorders. In conclusion, ADRs caused by immunostimulants especially interferons have higher tendency to be reported in Egypt especially in the middle-aged group. Additionally, the study has shown that serious ADRs of antineoplastic and immunomodulating agents were more likely to be reported by healthcare professionals rather than consumers.