Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo.

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Covid-19 Vaccine safety and adverse event analysis from Pakistan

Covid immunization commenced on 2nd Feb 2021 in Pakistan and as of 7th Sep 2021, over 84 million vaccine doses were administered in Pakistan, of which 72% procured by the government, 22% received through Covax and 6% were donated. The vaccines rolled out nationally included: Sinopharm, Sinovac and CanSinoBIO (China), AstraZeneca (UK), Moderna and Pfizer (USA), Sputnik (Russia), and PakVac (China/Pakistan). About half of the eligible population in Pakistan (63 m) had received at least one dose of Covid vaccine as of Sep 2021. Pakistan National Pharmacovigilance Centre (PNPC) in coordination with WHO, MHRA and Uppsala Monitoring Centre (UMC) established pharmacovigilance centers across Pakistan. The Covid vaccine AEFIs in Pakistan were mainly reported via NIMS (National Immunization Management System), COVIM (Covid-19 Vaccine Inventory Management System), 1166 freephone helpline and MedSafety. There have been 39,291 ADRs reported as of 30th Sept 2021, where most reported after the first dose (n = 27,108) and within 24-72 h of immunization (n = 27,591). Fever or shivering accounted for most AEFI (35%) followed by injection-site pain or redness (28%), headache (26%), nausea/vomiting (4%), and diarrhoea (3%). 24 serious AEFIs were also reported and investigated in detail by the National AEFI review committee. The rate of AEFIs reports ranged from 0.27 to 0.79 per 1000 for various Covid vaccines in Pakistan that was significantly lower than the rates in UK (~4 per 1000), primarily atrributed to underreporting of cases in Pakistan. Finally, Covid vaccines were well tolerated and no significant cause for concern was flagged up in Pakistan's Covid vaccine surveillance system concluding overall benefits outweighed risks.Copyright © 2022

Efficacy and Safety of Ixekizumab in Chinese Patients with Moderate-to-Severe Plaque Psoriasis: 60-Week Results from a Phase 3 Study

Objective: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis. This phase 3, multicenter, randomized, double-blind, placebo-controlled trial (NCT03364309;registered December 6, 2017) evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis. Method(s): 438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks (IXE Q2W, n = 176), 80 mg ixekizumab every 4 weeks (IXE Q4W, n = 174), or placebo (n = 88). Efficacy was assessed by evaluating the static Physician's Global Assessment score of 0 or 1 (sPGA [0,1]) and Psoriasis Area and Severity Index (PASI) 75/90/100 responses, and nonresponder imputation was used for handling missing data. The safety profile was evaluated by assessing treatment emergent adverse events (AEs) and serious AEs. Result(s): At week 12, the sPGA (0,1) response rates were 3.4%, 79.9%, and 86.4% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%, 87.4%/75.9%/29.3%, and 93.8%/82.4%/33.0% in the placebo, IXE Q4W, and IXE Q2W groups, respectively. Ixekizumab led to rapid PASI 50 responses, as early as week 1, whereas PASI 75 and sPGA (0,1) responses were observed from week 2. sPGA (0,1) and sPGA (0) responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs. placebo. The safety profile was consistent with previous studies of ixekizumab in psoriasis. Conclusion(s): Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs, in Chinese patients with moderate-to-severe plaque psoriasis. Copyright © 2022 International Journal of Dermatology and Venereology. All right reserved.

Allergology and the challenges we are facing today

The care of patients suffering from allergological disorders is a clinical priority of the Karlsruhe Dermatology Clinic. Previously, the diagnostic focus was on detection of type-IV-sensitisation. However, due to increasing demand, the diagnosis of hymenoptera venom allergies has become a much more prominent issue. The direct impact of recent events on the allergological activity in the Karlsruhe Dermatology Clinic, was, with regard to the clarification on a potential allergy to a Covid 19 vaccine, recently becoming even more noticeable. Copyright © 2022 Georg Thieme Verlag. All rights reserved.