1,720,982 research outputs found
Is There a Risk of Lymphoma Associated With Anti-tumor Necrosis Factor Drugs in Patients With Inflammatory Bowel Disease? A Systematic Review of Observational Studies
Full text linkBackground: Inflammatory bowel diseases (IBDs) are generally not considered a risk factor for the development of lymphoma. When considering IBD treatments, there is good evidence supporting thiopurines (azathioprine, 6-mercaptopurine) as a risk factor for lymphoma. Conversely, the association between the use of anti-TNF agents and the development of lymphoma remains undetermined. In this systematic review, we analyzed the evidence coming from observational studies supporting an association between the use of anti-TNF drugs and lymphoma in patients with IBDs. Methods: This systematic review was performed according with MOOSE and PRISMA statements. We searched observational studies conducted on IBD patients, using MEDLINE, EMBASE, and Google Scholar, published in English language, within the period ranging from January 1st, 1999 to June 30th, 2018. An assessment of the methodologic shortcomings of selected studies was performed as well. Results: Fourteen studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drug with lymphoma or groups of cancers including lymphoma. However, the methodologic shortcomings of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not. Conclusions: Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients
The usefulness of listening social media for pharmacovigilance purposes: a systematic review
Full text linkIntroduction: Social media mining could be a possible strategy to retrieve drug safety information. The mining of social media is a complex process under progressive evolution, falling into three broad categories: listening (safety data reporting), engaging (follow-up), and broadcasting (risk communication). This systematic review is aimed at evaluating the usefulness and quality of proto-signals by social media listening. Areas covered: In this systematic search, performed according to MOOSE and PRISMA statements, we selected studies, published in MEDLINE, EMBASE, and Google Scholar until 31 December 2017, that listened at least one social media to identify proto-adverse drug events and proto-signals. Expert opinion: The selected 38 studies identified serious and unexpected proto-adverse drug events characterized by poorer information quality as compared with spontaneous reporting databases. This feature allows rarely the evaluation of causal relationships. Proto-signals identified by social media listening had the potential of anticipating pre-specified known signals in only six studies. Moreover, the personal perception of patients reported in social media could be used to implement effective risk communication strategies. However, signal detection in social media cannot be currently recommended for routine pharmacovigilance, due to logistic and technical issues.</p
Tixagevimab + cilgavimab against SARS-CoV-2: the preclinical and clinical development and real-world evidence
No full textIntroductionDirect-acting SARS-CoV-2 antiviral monoclonal antibodies have been an integral part of therapeutic strategies against COVID-19 pandemic. The monoclonal strategy was jeopardized by the emergence of new variants and resistant strains, making many monoclonal antibodies quickly obsolete. Nevertheless, a possible strategy consists in the use of antibody cocktails and the development of the cilgavimab + tixagevimab in combination is placed in this context.Areas coveredIn this review, we describe the development of the cilgavimab + tixagevimab cocktail, from pre-clinical to real-world evidence.Expert opinionThe pre-clinical and clinical development of cilgavimab + tixagevimab followed a similar path to that of the antibodies developed in the earlier stages of the pandemic. Both antibodies have been developed from convalescent plasma and have been shown to be effective in clinical trials in prophylaxis and in early therapy. This cocktail has found its position in therapy especially in immunocompromised subjects for whom vaccine prevention is not feasible. The cocktail strategy, together with a more stable pandemic situation, could ensure a certain longevity to the drug against resistance, especially when compared with that of other antibodies. Recently emerged Omicron sub-lineages have demonstrated the ability to escape this cocktail's activity and so the future of this treatment could be compromised
Signals of Possibly Persistent Gustatory, Olfactory and Auditory Adverse Drug Reactions to Antibiotic Drugs: A Disproportionality Analysis Using the EudraVigilance Database
No full textBackground In 2018, the European Medicines Agency issued some risk minimisation measures related to unresolved adverse drug reactions (ADRs) reported for fluoroquinolones, including sensory ADRs. Spontaneous reporting databases frequently report unresolved outcomes for gustatory, olfactory and auditory (GOA) ADRs. However, such a high volume of unresolved GOA ADRs could reflect an under-investigated clinical issue or an intrinsic difficulty in the outcome assessment. Objectives The objectives of the study were: (1) to investigate whether unresolved outcomes are reported more frequently for GOA ADRs than for other ADRs to systemic antibiotics and (2) to identify possible signals of unresolved GOA ADRs for systemic antibiotics. Methods We used the EudraVigilance database to extract the number of ADRs to systemic antibiotics of the Anatomical Therapeutic Chemical class J01 up to February 2019. We classified ADRs in "non-GOA ADRs" and "GOA ADRs". Adverse drug reactions were categorised in three groups according to the outcome: defined, persistent/permanent (unresolved) and undetermined ADRs. We performed disproportionality analyses with the case/non-case methodology, by calculating the crude reporting odds ratio (ROR) and 95% confidence interval (CI). Cases were all persistent/permanent ADRs, and non-cases were defined and undetermined ADRs. For the first objective, index groups were gustatory or olfactory or auditory ADRs, while reference group included all non-GOA ADRs. For the second objective, we performed a disproportionality analysis by using the sub-set of GOA ADRs. Index and reference groups varied with subgroups of drugs and drug class, so that each drug and drug class was compared with the others. We conducted two sensitivity analyses for each analysis by varying the case definition. Results We extracted 748,798 ADRs, including 10,770 GOA ADRs. The first analysis showed that GOA ADRs were reported more frequently as unresolved events compared with all other ADRs (ROR: 2.68 95% CI 2.51-2.85; ROR: 5.20 95% CI 4.66-5.81; and ROR: 2.64 (95% CI 2.51-2.79, respectively). Gustatory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.69, 95% CI 1.18-2.41, p = 0.0038), azithromycin (ROR: 2.07, 95% CI 1.58-2.72, p < 0.0001) and levofloxacin (ROR: 1.59, 95% CI 1.22-2.07, p < 0.001) compared with GOA ADRs of all other antibiotics. Olfactory ADRs were reported more frequently as unresolved for doxycycline (ROR: 2.4, 95% CI 1.26-4.58, p = 0.0078) and levofloxacin (ROR: 1.92, 95% CI 1.28-2.86, p = 0.0014). Auditory ADRs were reported more frequently as unresolved for doxycycline (ROR: 1.52, 95% CI 1.09-2.12, p = 0.013) and clarithromycin (ROR: 1.31, 95% CI 1.09-1.59, p = 0.0049). Conclusions We tested and used an appropriate expected frequency standard, which allows us to identify possible signals of unresolved GOA ADRs to antibiotic drugs in the EudraVigilance database. This approach could be used to generate signals of persistent or even irreversible events for other drugs or adverse reactions. However, these signals must be confirmed with a thorough clinical assessment
Editorial: Biologic drugs in immune-mediated inflammatory diseases, validation, drug-utilization, effectiveness, regulation, costs, and safety in the real-world
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Communicating Drug Safety
No full textPromoting safety of medications is imperative for optimal use, and the communication of the risk is entrusted to communicators. The communication of the risk of medicine requires peculiar expertise that is different from communications about its benefit. The identification of a risk related to a medicinal product is a dynamic process that involves the acquisition of information that progressively transforms into knowledge. In the initial stages of this process, the risk is often only potential but this uncertainty still requires caution. Uncertain risks are frequently matter of communication, and the magnitude of this uncertainty often drives the risk communication itself as the main subject. A message has to be tailored to the attitude and concerns of the target audience for achieving the best effects. Otherwise, uncertainties and hesitancies could persist even after the confirmation of the absence of a risk or could spread throughout media with consequent possible inappropriate use of drugs or therapeutic failure of medicines. In this regard, case studies such as measles vaccination and autism and the COVID-19 infodemic are paradigmatic examples. In risk communication about medicines, it is important to identify the subjects involved, define their roles (senders or receivers) and characteristics, to build the message and its content, and choosing the appropriate media for conveying the message. Several expertise is also required, including rhetoric, ethics, social sciences, and pharmacoepidemiology
Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects
Full text linkExposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about drug-induced neonatal syndromes
Preclinical discovery and development of the casirivimab + imdevimab cocktail for the treatment of novel coronavirus infection: the rise and fall
No full textIntroduction The ongoing COVID19 pandemic represents an unprecedented opportunity to test the feasibility of monoclonal antibody (mAb) therapies against respiratory viruses. While many hurdles were easily predictable (e.g. time to develop, scalability, and economic sustainability), mAb cocktails (i.e. the combination of two mAbs) were finally deployed in 2021, one year after the beginning of the pandemic. Of them, the REGN-COV-2 cocktail was likely the most successful experience and contributed at saving lives at the time of the wave sustained by the Delta variant of concern (VOC). Areas Covered Herein, the authors review the preclinical and clinical history of the casirivimab + imdevimab cocktail for the treatment of novel coronavirus infection. The authors furthermore provide the reader with their perspectives on this cocktail including its current place in the treatment armamentarium. Expert opinion Unfortunately, results from clinical trials highlighted a very limited efficacy in inpatients; furthermore, the current evidence with regards to its lack of effectiveness against the current dominant VOC (omicron) suggests a very limited use of these drugs in the future. In the authors' opinion, this story reminds us of the limitations of mAb therapies in pandemic settings, and of the inferiority of monoclonal versus polyclonal antibody-based therapeutics in such scenarios
Diabetes drugs and the incidence of solid cancers: a survey of the current evidence
Full text linkIntroduction: The evaluation of the relationship between the use of antidiabetic drug and the occurrence of cancer is extremely challenging, both from the clinical and pharmacoepidemiological standpoint. This narrative review described the current evidence supporting a relationship between the use of antidiabetic drugs and the incidence of solid cancers. Areas covered: Data from pharmacoepidemiological studies on cancer incidence were presented for the main antidiabetic drugs and drug classes, including human insulin and insulin analogues, metformin, sulfonylureas, glinides, alpha-glucosidase inhibitors, thiazolidinediones, incretin mimetics, and sodium glucose co-transporter 2 inhibitors. The relationship between the use of antidiabetics and the incidence of solid cancer was described in strata by any cancer and by organ-specific cancer and by drug and by drug classes. Information supporting biological evidence and putative mechanisms were also provided. Expert opinion: The history of exploration of the relationship between antidiabetic drugs and the risk of solid cancers has showed several issues. Unrecognized biases and misinterpretations of study results have had important consequences that delayed the identification of actual risk and benefits of the use of antidiabetic drugs associated with cancer occurrence or progression. The lesson learned from the past should address the future research in this area, since in the majority of cases findings are controversial and confirmatory studies are warranted
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