1,721,067 research outputs found
On criteria to evaluate the therapeutic innovation of drugs
No full textAs authors of two papers proposing the“old”algorithm to assess thetherapeutic innovation of the medicines approved by the EM(E)Abetween 1995 and 2003,1,2we have read with great interest and curi-osity the paper by Filomena Fortinguerra et al. entitled“Using GRADEmethodology to assess innovation of new medicinal products inItaly.”3These authors rightly write that the Italian Medicines Agency(AIFA) was the first regulatory body to introduce a method foracknowledging and ranking the therapeutic innovation when itadopted our algorithm in 2007.4As former chairman (NM) andmember (DM), on behalf of AIFA, of the 2007-AIFA/Industry workinggroup commissioned to support such adoption, we had to arrange afew significant changes on the initial published algorithm. The mostimportant fruit of such bilateral effort was creating the category of“potential therapeutic innovation.
Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice
Full text linkPurpose: Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient’s own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting. Methods: We performed a retrospective observational study, collecting all the reports in EU (EudraVigilance, EV) and US (FAERS) databases of ADRs regarding axicabtagene ciloleucel and tisagenlecleucel. Both descriptive and statistical analyses were performed, the latter by using Reporting Odds Ratio (ROR). Results: A total number of 1426 reports of suspected ADRs were retrieved in EudraVigilance and FAERS. Patients’ reported age reflected the age range for which the drugs are approved (18–64 years for axicabtagene ciloleucel and patients aged under 25 years for tisagenlecleucel). The most reported event was cytokine release syndrome (CRS), 185 events for tisagenlecleucel and 462 for axicabtagene ciloleucel in FAERS and 137 and 498, respectively, in EudraVigilance. A disproportionality was found comparing axicabtagene ciloleucel with tisagenlecleucel for the above-mentioned event: EV ROR 2.47, 95% CI 2.22–2.74, FAERS 1.89, 1.70–2.10. Conclusion: CRS represents the major problem with the administration of CAR-T therapies. Our analysis has not revealed new ADRs; however, it supports the safety profile of CAR-T with new data from real clinical setting
Direct-acting oral anticoagulants and alopecia: The valuable support of postmarketing data
No full textLittle is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, seriousness and dechallenge/rechallenge outcome was carried out. For each report, the time-to-onset was evaluated and the causality was assessed by using Naranjo algorithm. Overall, 1316 reports were retrieved, most concerning rivaroxaban (58.8%); 80% of the reports were related to females, in particular to those aged ≥65 years (23.1%). The median value of the time-to-onset was 28 days, with an interquartile range of 63 days. In 54.3% of the reports the causality was assessed as possible. In conclusion, a possible association could exist between DOACs administration and alopecia, but further observational studies are needed to confirm these findings
Safety of COVID-19 vaccines in pregnancy: a VAERS based analysis
Full text linkPurpose: Since vaccination against COVID-19 is recommended in pregnant people, we aimed to provide further evidence on the safety profile of COVID-19 vaccines in pregnancy. Methods: Data on COVID-19 vaccines adverse events following immunizations (AEFIs) in pregnant people were retrieved from the open-access Vaccine Adverse Event Reporting System (VAERS) from December 2020 to April 2022. Results: From December 2020 to April 1, 2022, a total of 4,869 reports involving pregnant women at COVID-19 vaccination were reported to VAERS. Among vaccines recipients, most belonged to the age group between 30 and 39 years old (3,029; 62.21%) and nearly half experienced an adverse event within 48 h of immunization (2,344; 48.14%). Overall, 21,816 suspected adverse reactions associated with COVID-19 vaccines were reported, and for as many as 80.43% of patients, they were described as non-serious. Most reactions occurred after administration of the mRNA-1273 (53.34%) and the BNT162b2 (40.68%) vaccines, while only a small proportion were related to the Johnson & Johnson’s vaccine (5.69%). The most common non-pregnancy specific adverse events were headache (482; 2.21%), fatigue (472; 2.16%), and pyrexia (436; 2.00%), while adverse pregnancy outcomes with the highest reporting rate were abortions spontaneous (762; 3.49%), and vaginal haemorrhage (229; 1.05%). Conclusion: This post-marketing survey on VAERS data have provided updated evidence on the safety of COVID-19 vaccines during pregnancy, thus supporting clinicians in recommending maternal immunization
Safety Profile of Molnupiravir in the Treatment of COVID-19: A Descriptive Study Based on FAERS Data
Full text linkConcerns have been raised about the actual benefit and safety of molnupiravir, a new antiviral treatment for coronavirus disease 2019 (COVID-19). In order to provide additional evidence to support its use, we aimed to evaluate the real safety profile based on post-marketing pharmacovigilance data. Molnupiravir safety data were captured from the FDA Adverse Event Reporting System (FAERS). We performed a descriptive analysis of the baseline demographic characteristics of patients who experienced at least one adverse drug reaction (ADRs) related to molnupiravir, and then evaluated those most frequently reported. As of 31 March 2022, 612 reports of ADRs related to molnupiravir were submitted to the FDA, 301 (49.18%) were related to females and 281 (45.92%) to males. Most reports (524; 85.62%) were submitted by healthcare professionals and 345 (56.37%) concerned serious outcomes. The most common reported ADRs were diarrhoea (57; 4.51%), rash (36; 2.85), nausea (29; 2.30%), and COVID-19 pneumonia (22; 1.74%). The most frequent adverse reactions reported with molnupiravir in the U.S. post-marketing experience are consistent with the safety evaluation of the antiviral medicine. Even if no evident safety concerns emerged, an unexpectedly high rate of serious adverse reactions together with a few cases of potential new adverse reactions occurred
Safety profile of hydroxychloroquine used off-label for the treatment of patients with COVID-19: A descriptive study based on EudraVigilance data
No full textAt the beginning of the COVID-19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID-19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off-label for the treatment of COVID-19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases-9.97%-with COVID-19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID-19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision-related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off-label use in the treatment of COVID-19 disease
Removal of the EMA orphan designation upon request of the sponsor: cui prodest?
No full textPurpose: Various incentives are provided by the European Medicines Agency (EMA) to facilitate the development and marketing of orphan drugs. A 10-year period of market exclusivity is reserved to an orphan medicinal product. Sometimes, the sponsor renounces the designation before the expiration of that standard period. Our aim was to focus on these premature withdrawals. Methods: We retrieved all the molecules included in the Community Register of Orphan Medicinal Products for Human Use from 2000 to November 2020. We considered the active substance, therapeutic indication, sponsor, year of designation, year of approval of the corresponding medicinal product, and that of the withdrawal of the orphan designation, if occurred. Results: Overall, 2350 orphan designations were approved from 2000 to November 2020. Of these, 141 have been marketed. Premature withdrawal of orphan designation concerned 23 drugs (20 being antineoplastic agents), corresponding to 16 medicinal products. These withdrawals occurred after almost 2 years (range <1–7 years). Conclusions: A not negligible fraction of marketed orphan medicinal products underwent premature removal of their orphan designation. No motivation is requested by the EMA for this renouncement, although the peculiarity of the orphan medicinal products would need a greater transparency. We can only speculate about possible compensations in support of this decision, for instance in terms of commercial agreements between pharmaceutical companies, giving way to alternative products, as a couple of examples suggest. An open debate on this topic among members of academia, regulatory bodies, price and reimbursements committees, and pharmaceutical industry representatives will be welcome
Human papilloma virus vaccination in males: A pharmacovigilance study on the Vaccine Adverse Event Reporting System
No full textAims: Human papilloma virus (HPV) is 1 of the most common sexually transmitted infection responsible for different types of cancer: cervical, penile, vulvar, anal and oropharyngeal. It can affect both males and females. Our aim was to enrich the knowledge on the safety profiles of HPV vaccines in the male population. Methods: We reviewed all the reports of adverse events following immunization (AEFI) present in the US Vaccine Adverse Event Reporting System from 1 January 2006 to 30 September 2018. Statistical data mining was performed using the reporting odds ratio with 95% confidence interval in order to detect disproportionality in reporting. Results: A total of 5493 reports of AEFI were retrieved. The events most reported and that proportionally occurred more frequently with HPV vaccines than with others in males were: syncope (n = 701, reporting odds ratio = 2.85, 95% confidence interval [1.41–5.76p), loss of consciousness (n = 425, 2.79 [1.36–5.72]) and fall (n = 272, 3.54 [2.00–6.26]). Conclusion: Most of the AEFIs were already reported in premarketing clinical trials and acknowledged for the corresponding vaccines. A disproportionate reporting was found for some of these events including syncope. The HPV vaccines are generally well tolerated in males, although limitations own of spontaneous reporting should be considered
Level of therapeutic innovation from the registration studies of the new drugs for the prophylaxis of migraine
Full text linkWhat is known and objective: Migraine is one of the most prevalent and disabling medical illnesses. Preventive drugs are used to reduce the frequency, severity, and duration of attacks. Most patients were no longer on their medication due to contraindications or poor clinical response. Therefore, there is need for novel prophylactic agents for migraine. New preventive treatments are those of the class of calcitonin gene related peptide (CGRP)-targeting therapies. We aimed to assess the real level of therapeutic innovation of these new drugs. Methods: The information on the new drugs was collected from several documents, including the European public assessment reports. The level of therapeutic innovation was assessed with the algorithm published by some of us in 2006. Results: All new approved drugs (eptinezumab, galcanezumab, fremanezumab, erenumab) are indicated for the prophylaxis of migraine in adults who have at least four migraine days for month. All these drugs have been tested only in comparison to placebo. Their level of therapeutic innovation was only modest, that is, the lowest value of our algorithm. Discussion: The new monoclonal antibodies of the class of CGRP targeting therapies have been authorized with efficacy data only against placebo. They do not offer additional clinical benefits compared to available therapies for the prevention of migraine attacks, with the exception of a lower frequency of administration and a more rapid effect. All this assigns to these drugs only a modest role in therapy according to our algorithm for therapeutic innovation with a significantly higher cost than similar therapies
Drug-induced disseminated intravascular coagulation: a pharmacovigilance study on World Health Organization’s database
Full text linkBackground: Disseminated intravascular coagulation (DIC) occurs in several clinical conditions, including drug therapy. We aim to investigate the association between the administration of several drug classes and the onset of DIC by using the reports of Adverse Drug Reactions (ADR) collected in Vigibase, the World Health Organization (WHO) database of ADR. Methods: We collected reports of drug-related DIC from 1968 to September 2015, classified in Vigibase according to the MedDRA (Medical Dictionary for Regulatory Activities) term “Disseminated intravascular coagulation”. A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% Confidence Interval (CI95%) was performed. Results: Overall, 4653 reports of drug-associated DIC were retrieved and the 75.9% of them was serious according to WHO seriousness criteria. DIC was significantly (ROR > 1, lower limit of CI95% > 1) associated with 88 drugs, mainly antineoplastic agents, antithrombotic agents and antibacterials for systemic use. Among of the most frequently reported individual drugs we found dabigatran (94 reports) ROR = 1.34 (CI95% 1.08–1.67), oxaliplatin and bevacizumab both with 75 reports and ROR = 1.77 (1.38–2.27) and 2.02 (1.57–2.61), respectively. Conclusion: A substantial number of drugs, widely used in the clinical practice, may be associated with the potential occurrence of DIC. For many of these drugs, the ADR is not acknowledged in the corresponding Summary of Product Characteristics. The high number of drugs involved underlines the importance of evaluate this condition such as an ADR that might occur during drug therapy
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