Global Pharmacovigilance Research Articles

1056-P: Reported Pregnancy Outcomes with Insulin Glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) : Post-Marketing Survey of Pharmacovigilance Data

Background: Good metabolic control during pregnancy is crucial for people with diabetes to prevent adverse events associated with hyperglycemia. Gla-300, a long-acting basal insulin (BI) analog, provides similar glycemic control and less hypoglycemia versus the first-generation BI Gla-100. We examined real-life safety of insulin glargine use in pregnancy. Methods: Cumulative searches of the Sanofi global pharmacovigilance database for Gla-100/Gla-300 exposures in pregnancy were performed using Medical Dictionary for Regulatory Activities terms, from database initiation to March 9, 2021. Results: Searches found 4936 (2370 solicited, 2566 unsolicited; 71 countries) exposures to Gla-100 and 246 (66 solicited, 180 unsolicited; 44 countries) for Gla-300 (Table) . Cumulative exposure was 89 million and 7.9 million person-years for Gla-100 and Gla-300, respectively. Congenital, familial, and genetic anomalies were rare (2.6% Gla-100; 2.0% Gla-300) , in line with general population rates (3-5%) . Spontaneous abortion rates were low (3.0% Gla-100; 2.8% Gla-300) , which is also in line with the general population (˜10%) . Conclusion: Rates of congenital anomalies and spontaneous abortions for Gla-100 and Gla-300 were consistent with the general population. The results indicate no safety issues with insulin glargine use during pregnancy. Disclosure J.Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. C.Bassole: Employee; Sanofi. M.Duverne: Employee; Sanofi. Z.Doder: None. H.Schoepper: None. Funding Sanofi

Pulmonary hypertension reported with immune checkpoint inhibitors: a pharmacovigilance study.

Immune checkpoint inhibitors (ICI) restore immune response against cancer cells that can lead to immune-related adverse effects. While cardiovascular immune-related adverse effects are known to be associated with checkpoint inhibitors, recent case reports have raised concerns about the potential association with pulmonary hypertension (PH). By using the global pharmacovigilance database VigiBase, we investigated the onset of PH associated with ICI and propose a comprehensive description of the 42 cases of PH reported with ICI recorded in this database. Through this study and review of the cases published in the literature, we discuss the possible link between PH and ICI in the context of cancer in order to better understand this rare but potentially fatal event.

T Helper 2 IL-4/IL-13 Dual Blockade with Dupilumab Is Linked to Some Emergent T Helper 17‒Type Diseases, Including Seronegative Arthritis and Enthesitis/Enthesopathy, but Not to Humoral Autoimmune Diseases

Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns of immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) and T helper 2‒mediated disorders and humoral autoimmune pattern diseases, using VigiBase, the World Health Organization's global pharmacovigilance of adverse drug reactions. Several bioinformatics databases and repositories were mined to couple dupilumab-related immunopharmacovigilance with molecular cascades relevant to reported findings. A total of 37,848 dupilumab adverse drug reaction cases were reported, with skin, eye, and musculoskeletal systems most affected. Seronegative arthritis (OR= 9.61), psoriasis (OR= 1.48), enthesitis/enthesopathy (OR= 12.65), and iridocyclitis (OR= 3.77) were highly associated. However, ankylosing spondylitis and inflammatory bowel disease were not conclusively associated. Overall, classic polygenic humoral‒mediated autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus were not associated with dupilumab use. Pathway analysis identified several biological pathways potentially involved in dupilumab‒associated adverse drug reactions, including the fibroblast GF receptor (in particular, FGFR2) pathway. MicroRNAs analysis revealed the potential involvement of hsa-miR-21-5p and hsa-miR-335-5p. In conclusion, IL-4/IL-13 blockers are not unexpectedly protective against humoral autoimmune diseases but dynamically skew immune responses toward some IL-23/IL-17 cytokine pathway‒related diseases. IL-4/13 axis also plays a role in homeostatic tissue repair and we noted evidence for a link with ocular and arterial pathology.

IDF21-0195 Reported pregnancy outcomes with insulin glargine 300 U/mL: a post-marketing survey of pharmacovigilance data

Background: It is essential for people with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. To attain blood glucose control during pregnancy, insulin glargine and other basal insulins are treatment options. Insulin glargine 300 U/mL (Gla-300) is a second-generation basal insulin analogue that has been shown to provide similar glycaemic control with less hypoglycaemia versus the first-generation basal insulin analogue, insulin glargine 100 U/mL. However, there are currently no randomised controlled trials specifically designed to investigate the use of Gla-300 during pregnancy. Aim: The present analysis aims to examine the safety of Gla-300 use in women with diabetes during pregnancy in real-life practice, using post-marketing pharmacovigilance data. Method: Using Medical Dictionary for Regulatory Activities (MedDRA) terms, a cumulative search of Sanofi’s global pharmacovigilance database was performed to identify pregnancy outcomes during Gla-300 use, up until 9 March 2021. Results: Post-marketing searches identified 246 cases for analysis (66 solicited, 180 unsolicited) (Table) from 44 countries. Cumulative exposure to Gla-300 was 7.9 million person-years. Reporting rates for adverse events of specific interest were 31.1/1,000,000 person-years. Congenital, familial, and genetic anomalies were rare with Gla-300 (5, 2.0%: one cardiac, one genito-urinary, one musculoskeletal and connective tissues, one respiratory, and one gastrointestinal tract disorder); this is consistent with the rate of birth defects reported for the general population, which is ∼3–5% of all live births. Spontaneous abortions were also rare (7, 2.8%), consistent with miscarriage rates observed in the general population (≥∼10%). Table.Tabled 1MedDRA search termNumber of events (%)a,bReporting ratec.d,e (events per 1,000,000 person-years)Total number of pregnancy exposures (including 1 exposure via father)246 (N/A)31.1Abortion (induced)0 (0.0)0.00Abortion (spontaneous)7 (2.8)0.89Abortion (not specified as induced or spontaneous)4 (1.6)0.51Anembryonic gestation1 (0.4)0.13Congenital, familial, and genetic disorders5 (2.0)0.63Ectopic pregnancy0 (0.0)0.00Exposures via breast milk8 (3.3)1.01Premature birth7 (2.8)0.89Postmature birth0 (0.0)0.00Stillbirth1 (0.4)0.13Live birth/unknown or missing outcome237 (96.3)30.00 Open table in a new tab aSome cases may be counted more than once owing to multiple events reported in one case; bPercentage calculation is based on total number of pregnancy/lactation related cases (246); cThe reporting rate is based on cumulative exposure as there are no data by gender; dData collected from IMS Health; eCumulative exposure to Gla-300 (7.9 million person-years) based on data collected up to 26 January 2021. MedDRA, Medical Dictionary for Regulatory Activities; N/A, not applicable Discussion: Rates of spontaneous abortions and congenital anomalies were low for Gla-300 and consistent with rates in the general population. Use of Gla-300 during pregnancy was not associated with specific adverse events/congenital abnormalities. These results indicate no safety issues with use of Gla-300 during pregnancy.

Tamsulosin and risk of priapism: A causality assessment using Austin Bradford Hill Criteria.

Tamsulosin hydrochloride, a selective alpha‐adrenergic blocking agent has been previously associated with priapism. Priapism is a medically serious condition that, if not intervened, can cause permanent erectile dysfunction. This study was conducted to investigate whether the association of tamsulosin and priapism is causal. All currently available evidence such as experimental, biological, toxicological, published studies, and safety data mined from the WHO global pharmacovigilance database was systematically organized into the Austin Bradford Hill causality assessment framework. In the international pharmacovigilance database, a strong association between tamsulosin and priapism (IC025 = 4.1; PRR025 = 19.9; ROR025 = 20) was observed. There were 122 cases of priapism associated with tamsulosin submitted to the database from 23 countries. In 87.7% of the cases, tamsulosin was reported as a ‘sole suspect,’ and in 50.8%, it was the only drug administered. In several patients, priapism resolved following discontinuation of tamsulosin and recurred after its reintroduction. Both in the published and unpublished data, for majority of the cases, the time to onset of priapism was within few days following the first intake of tamsulosin. Cases of priapism, particularly those published, were consistent in their clinical features with patients experiencing prolonged painful erection that required aspiration of cavernosal blood, irrigation of the corpora cavernosa, and treatment with vasopressors. Other alpha‐adrenergic blocking agents that are structurally analogous with tamsulosin have also been associated with priapism. In several cases, tamsulosin was used off‐label, for the treatment of ureteral calculi expulsion. Eight patients experienced priapism that ended up with serious complications such as ejaculation disorders and erectile dysfunction. The currently available totality of evidence suggests that the association of tamsulosin and priapism is causal. Healthcare professionals are therefore recommended to cautiously prescribe tamsulosin and ensure that consumers are aware of the potential risk of priapism.

Association between myocarditis and antipsychotics other than clozapine: a systematic literature review and a pharmacovigilance study using VigiBase

ABSTRACT Introduction Pharmacovigilance studies have definitely established that clozapine can cause myocarditis. Two published reviews suggested that on rare occasions other antipsychotics may induce myocarditis. Areas covered This review explored myocarditis associated with antipsychotics other than clozapine by conducting a systematic search of the literature and critically analyzing the current data in VigiBase compared to the data on clozapine-associated myocarditis. VigiBase is the World Health Organization’s global pharmacovigilance database that uses a statistical signal for associations with a logarithmic measure of disproportionality called the information component (IC). Expert opinion For quetiapine, VigiBase provided 106 reports of myocarditis and a significant statistical signal (IC = 1.8; IC025 = 1.5) which was confounded by 48% (51/106) with clozapine co-prescription. Combining the literature and VigiBase cases provided five probable myocarditis cases during quetiapine monotherapy (4 after overdose or rapid titration). For olanzapine, VigiBase provided 107 reports of myocarditis and a significant statistical signal (IC = 2.1; IC025 = 1.8) probably explained by 77% (82/107) using clozapine co-prescription. Combining the literature and VigiBase cases provided one probable myocarditis case during olanzapine monotherapy. Combining the literature and VigiBase provided another three probable cases during therapy with other antipsychotics during overdose or titration with a high dose.

Development and Implementation of an Online Global Pharmacovigilance Certificate Program During the COVID-19 Pandemic.

Pharmacovigilance plays a lifesaving role in the practice of medicine. In 2021, during the Coronavirus Infectious Disease 2019 (COVID-19) pandemic, Loyola University Chicago launched a graduate-level Pharmacovigilance Certificate Program (PV-CERT) and a pre-professional non-graduate Pharmacovigilance Certificate Course (EPEC-PV), to provide students a comprehensive and contemporary understanding of the principles and practices of pharmacovigilance. Formal training in pharmacovigilance through this course provided a structured understanding of how safety data are generated through clinical trials and from real-world evidence as well as the regulatory environment in which data are monitored and interpreted. Pharmacovigilance training is of critical importance, especially during the COVID-19 pandemic, during which several drugs were re-purposed for the management of various stages of COVID-19 without conventional safety data. Moreover, the safety of currently-used vaccines is of concern in some populations. Although anticoagulants and antithrombotic medications are crucial in the management of COVID-19, a clear pharmacovigilance program on their use in this indication is not established. As the century progresses, new diseases and infectious agents will require novel therapies for which the evaluation of benefits versus risks will be as essential as it has been for the current COVID-19 pandemic. As such, the Loyola course and accompanying programs on pharmacovigilance will play a key role in educating the next generation of professionals in pursuing careers in the development of therapies that ultimately improve patient outcomes while maintaining rigorous safety standards.

Association between Antidepressant Use and Delirium in Older Adults: An Analysis of the World Health Organization's Global Pharmacovigilance Database

Association between Antidepressant Use and Delirium in Older Adults: An Analysis of the World Health Organization's Global Pharmacovigilance Database

Adverse event following vaccine surveillance in Kaduna State, Northwestern Nigeria (January 2018 -June 2019): analysis of health facility´s records.

IntroductionAdverse Events Following Immunization (AEFI) are one of the main reasons for inadequate immunization coverage in Kaduna State, and AEFI underreporting serves as a barrier to achieving goals of global pharmaco-vigilance for vaccine. The purpose of this study is to estimate the completeness of variables in the AEFI line-listing forms, calculate AEFI reporting rates by Local Government Areas & vaccine type and profile the reported cases according to their reactions.Methodswe conducted a descriptive, cross-sectional, retrospective study of primary surveillance records. We calculated AEFI reporting rates in the State and Local Government areas and AEFI Vaccine reaction rates to the various antigens. We used Binary logistic regression to determine the association between gender and vaccine reactions.Resultsseven thousand eight hundred and twenty-four (7,824) AEFI cases were reported. The completeness of variables on the filled AEFI line-list varied from 21% to 100%. The State had a high AEFI reporting rate of 9.09 per 10,000 administered doses. Fever (<38oC) was the main AEFI reaction. Severe AEFI cases accounted for only 0.89% of the total reported cases. Pentavalent vaccine was the suspect antigen responsible for the highest number of AEFI cases, with a vaccine reaction rate of 44.77 per 10,000 doses. The Zaria Local Government area had the highest AEFI reporting rate, while the Sanga Local Government area had the lowest AEFI reporting rate in the State. The difference between genders in the number of reported AEFI cases was not statistically significant (p>0.05). There were 35% higher odds of occurrence of bleeding among males than among females (aOR: 1.354; P-value: p=.012; 95% CI: 1.070-1.715; Nagelkerke-R2-: 0.003). The other reactions were not significantly related to gender.Conclusionour study shows a higher occurrence of severe AEFI in subjects undergoing pentavalent vaccine. Thiscaused the highest incidence of AEFI. There was no significant association between gender and AEFI reactions.

Comment on: Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study: reply

Comment on: Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study: reply

Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study

Risk of giant cell arteritis and polymyalgia rheumatica following COVID-19 vaccination: a global pharmacovigilance study

Adverse events associated with dupilumab in the World Health Organization pharmacovigilance database

To the Editor: Dupilumab is a monoclonal antibody targeting the interleukin 4/interleukin 13 pathway and is approved to treat atopic dermatitis. Dupilumab has shown a favorable safety profile in randomized controlled trials and observational cohorts but has been associated with a number of adverse events, including exacerbation of atopic dermatitis, eye disorders, or eosinophilia.1,2 Nevertheless, data are limited by short time frames. In order to assess adverse events associated with dupilumab, we conducted a pharmacovigilance study using Vigibase, the World Health Organization's global pharmacovigilance database.

Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase.

Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection. We carried out a comprehensive data mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the age-group of 45-64 years (with an IC0.25 of 0.17). Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab.

Safety profile of Dupilumab during pregnancy: a data mining and disproportionality analysis of over 37,000 reports from the WHO individual case safety reporting database (VigiBase™).

Atopic dermatitis, known also as atopic eczema, represents a commonly diagnosed, chronic or recurrent/relapsing inflammatory disorder. From a clinical point of view, it is characterized by acute flare-ups of intense itching, eczematous pruritic lesions involving dry skin. Dupilumab is the only biologic agent approved to treat moderate to severe course of atopic dermatitis, which can be particularly severe during pregnancy causing distress and impacting on maternal and fetal health. However, there is a dearth of data concerning the safety profile of Dupilumab during gestation. Therefore, we took advantage of a large global pharmacovigilance database. From inception up to March 9, 2021, 94,065 adverse drug reactions (ADRs) from 37,848 unique reports were retrieved. Of these, 36 reports related to pregnancy, puerperium and perinatal ADR could be extracted from the pharmacovigilance database. More than half of reports (n = 21; 58.3%) were spontaneous abortion, followed by other events, including exposure to the drug during the pregnancy (n = 8; 22.2%). Two cases of abortion were reported. No studied pregnancy, puerperium and perinatal ADR was found to be associated with the use of Dupilumab. The only OR significantly greater than 1 was the OR associated with the risk of developing heterotopic pregnancy (21.66 [95% CrI 2.95-159.02]) even if the IC was highly imprecise (1.45 [95% CrI from -2.34 to 3.09]), probably because of the single case of heterotopic pregnancy reported. In conclusion, Dupilumab use appears safe during gestation. Further studies are needed, especially to better understand the mechanisms underlying the pharmacological actions and ADR of Dupilumab.

A PHARMACOVIGILANCE STUDY OF HUMAN CHORIONIC GONADOTROPIN-ASSOCIATED ADVERSE EVENTS IN MALES

Human chorionic gonadotropin (hCG) is an exogenous analog of luteinizing hormone (LH). The only FDA-approved indication for males is to treat hypogonadotropic hypogonadism and cryptorchidism. hCG is used off-label to treat other conditions, including hypogonadism with various etiologies and infertility. Thus, little has been reported on the adverse side effects of hCG. We sought to explore the W.H.O pharmacovigilance database (VigiBase), the world's largest pharmacovigilance database, based on spontaneous individual case safety reports (ICSR), in order to report adverse events associated with the use of hCG. We conducted a pharmacovigilance study using VigiBase on hCG use in men. We used reporting odds ratio (ROR), a surrogate measure of association used in disproportionality analysis, with 95% confidence intervals (CI), and descriptive demographic statistics were calculated. Conclusively for ease of interpretation, related indications and adverse events were grouped. Furthermore, we ran sensitivity analyses on indications, age, and gender to mitigate uncertainty in our results. A total of 530 adverse events of hCG usage in men were identified; only 308(58.11%) had indication reported. Age demographics were; 157(29.62%) children, 241(45.47%) adults, 132(29.91%) unknown age. There was a significant disproportionally signal with dosing and administration errors 75(14.15%) (ROR, 5.313; 95% CI, 4.162-6.784), reproduction and fertility disorders 13(2.45%) (ROR, 12.117; 95% CI, 6.987-21.012), testicular and epididymal disorders 13(2.45%) (ROR, 102.245; 95% CI, 58.919-177.430), and penile disorders 4(0.75%) (ROR, 41.819; 95% CI, 15.627-111.908). In our pediatric sub-group, edema, whether facial, peripheral, or generalized, represented 12.73% of adverse events, with a significant disproportionally signal (ROR, 10.052; 95% CI, 5.579-18.115). Main indications included; 85(16.03%) hypogonadism, 74(13.96%) cryptorchidism, 41(7.73%) anabolic steroids and substance abuse, 32(6.03%) hypothalamo-pituitary disorders, 30(5.66%) infertility, and testicular failure. We report the first global pharmacovigilance study of hCG usage and adverse events in males. hCG appears to be associated with a spectrum of perhaps under-appreciated relevant physical side effects. Additionally, we noted a strong association of dosing and medication errors which raises concern about deficits in patient education and medication packaging for hCG, suggesting further investigational studies.

Drug-Induced Stuttering: Occurrence and Possible Pathways.

Background: Stuttering is a well-known condition that affects mainly children. Often, they recover as they get older. However, a drug-induced form of stuttering may occur at any age. The aim of the present study was to detect drugs that have been associated with stuttering and discuss the mechanisms involved.Method: A descriptive study based on reports submitted to the global pharmacovigilance database VigiBase of the WHO was conducted.Results: A total of 3,385 reports of dysphemia were retrieved from VigiBase. These reports were contributed by 51 countries. Antiepileptics, antidepressants, immunosuppressants, antipsychotics, and centrally acting sympathomimetics were among the most frequently implicated drugs.Conclusion: A wide variety of drugs has been linked to the occurrence or recurrence of stuttering. Several mechanisms, such as increased dopamine levels, reduction of GABA, anticholinergic properties of drugs, or changes in serotonin levels, have been associated with the development of drug-induced stuttering. Paradoxically, agents known to reduce stuttering in some people may induce it in others.

Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

Using an Automated Algorithm to Identify Potential Drug-Induced Liver Injury Cases in a Pharmacovigilance Database.

IntroductionDrug-induced liver injury (DILI) is the most frequent cause of acute liver failure in North America and Europe, but it is often missed because of unstandardized diagnostic methods and criteria. This study aimed to develop and validate an automated algorithm to identify potential DILI cases in routine pharmacovigilance (PV) activities.MethodsPost-marketing hepatic adverse events reported for a potentially hepatotoxic drug in a global PV database from 19 March 2017 to 18 June 2018 were assessed manually and with the automated algorithm. The algorithm provided case assessments by applying pre-specified criteria to all case data and narratives simultaneously.ResultsA total of 1456 cases were included for analysis and assessed manually. Sufficient data for algorithm assessment were available for 476 cases (32.7%). Of these cases, manual assessment identified 312 (65.5%) potential DILI cases while algorithm assessment identified 305 (64.1%) potential DILI cases. Comparison of manual and algorithm assessments demonstrated a sensitivity of 97.8% and a specificity of 79.3% for the algorithm. Given the prevalence of potential DILI cases in the population studied, the algorithm was calculated to have positive predictive value 56.3% and negative predictive value 99.2%. The time required for manual review compared to algorithm review suggested that application of the algorithm prior to manual screening would have resulted in a time savings of 42.2%.ConclusionAn automated algorithm to identify potential DILI cases was developed and successfully implemented. The algorithm demonstrated a high sensitivity, a high negative predictive value, along with significant efficiency and utility in a real-time PV database.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01856-x.

Higher Rates of COVID-19 but Less Severe Infections Reported for Patients on Il-4/Il-13 Blocker: A Big Data Analysis of the WHO Vigibase

Background: Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biological therapy is generally associated with an increased risk of infectious disease, prior studies have suggested Dupilumab may be protective. Objective: We investigated the link between Dupilumab therapy and SARS-CoV-2 infection.Methods: We carryied out a comprehensive data-mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. Results: Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the age-group of 45-64 years (with an IC0.25 of 0.17). Limitations: Limitations include: the heterogeneous nature of the database sources. Furthermore, a direct causal relationship cannot be inferred from the current investigation.Conclusion: Dupilumab use was found to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings.

Global Pharmacovigilance, challenges, and future considerations: West globe and East globe

Global Pharmacovigilance, challenges, and future considerations: West globe and East globe