scholarly journals Safety and reactogenicity of the adjuvanted recombinant zoster vaccine: experience from clinical trials and post-marketing surveillance

2021 ◽  
Vol 9 ◽  
pp. 251513552110574
Author(s):  
Joseph Fiore ◽  
Maribel Miranda Co-van der Mee ◽  
Andrés Maldonado ◽  
Lisa Glasser ◽  
Phil Watson
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Pooled Analysis ◽  
Cell Transplant ◽  
Zoster Vaccine ◽  
Phase 3 ◽  
Pivotal Phase ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Recombinant Zoster Vaccine

An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of herpes zoster. This paper reviews its safety and reactogenicity. A pooled analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in adults ⩾50 years found that more solicited adverse events (AEs) were reported with RZV than placebo. Injection site pain was the most common solicited AE (RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%, respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms were mild to moderate in intensity with a median duration of 2–3 days. The intensity of reactogenicity symptoms did not differ substantially after the first and second vaccine doses. The pooled analysis of the pivotal Phase-3 trials did not identify any clinically relevant differences in the overall incidence of serious adverse events (SAEs), fatal AEs or potential immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five studies of immunocompromised patients ⩾18 years (autologous stem cell transplant, human immunodeficiency virus, solid tumors, hematological malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056, NCT01767467, and NCT02058589) was consistent with that observed in the pivotal Phase-3 trials. There were no clinically relevant differences between RZV and placebo in the immunocompromised populations with regard to overall incidence of SAEs, fatal AEs, pIMDs, or AEs related to patients’ underlying condition. Post-marketing surveillance found that the most commonly reported AEs were consistent with the reactogenicity profile of the vaccine in clinical trials. Overall, the clinical safety data for RZV are reassuring. [Formula: see text]

scholarly journals Systematic analysis of protein targets associated with adverse events of drugs from clinical trials and post-marketing reports

2020 ◽  
Author(s):  
Ines A. Smit ◽  
Avid M. Afzal ◽  
Chad H. G. Allen ◽  
Fredrik Svensson ◽  
Thierry Hanser ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Adverse Event Reporting System ◽  
Quantitative Information ◽  
Carbonic Anhydrases ◽  
Systematic Analysis ◽  
Post Marketing Surveillance ◽  
Post Marketing

AbstractAdverse drug reactions (ADRs) are undesired effects of medicines that can harm patients and are a significant source of attrition in drug development. ADRs are anticipated by routinely screening drugs against secondary pharmacology protein panels. However, there is still a lack of quantitative information on the links between these off-target proteins and the risk of ADRs in humans. Here, we present a systematic analysis of associations between measured and predicted in vitro bioactivities of drugs, and adverse events (AEs) in humans from two sources of data: the Side Effect Resource (SIDER), derived from clinical trials, and the Food and Drug Administration Adverse Event Reporting System (FAERS), derived from post-marketing surveillance. The ratio of a drug’s in vitro potency against a given protein relative to its therapeutic unbound drug plasma concentration was used to select proteins most likely to be relevant to in vivo effects. In examining individual target bioactivities as predictors of AEs, we found a trade-off between the Positive Predictive Value and the fraction of drugs with AEs that can be detected, however considering sets of multiple targets for the same AE can help identify a greater fraction of AE-associated drugs. Of the 45 targets with statistically significant associations to AEs, 30 are included on existing safety target panels. The remaining 15 targets include 8 carbonic anhydrases, of which CA5B was significantly associated with cholestatic jaundice. We include the full quantitative data on associations between in vitro bioactivities and AEs in humans in this work, which can be used to make a more informed selection of safety profiling targets.

Abstract 14248: Efficacy and Safety of Bempedoic Acid in Patients Who Cannot Tolerate Statins: Pooled Analysis of 4 Phase 3 Clinical Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ulrich Laufs ◽  
Maciej Banach ◽  
Harold E Bays ◽  
Alberico L Catapano ◽  
P Barton Duell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Pooled Analysis ◽  
Lipid Lowering ◽  
Drug Discontinuation ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Statin Intolerance ◽  
Phase 3 ◽  
Additional Information

Introduction: Some patients cannot tolerate statins mainly because of statin-associated muscle symptoms (SAMS). Bempedoic acid (BA) is a prodrug activated in the liver and not in skeletal muscle. BA has been shown to significantly lower LDL-C by a mean of ~18% in patients receiving background maximally tolerated statins and a mean of ~25% in patients with statin intolerance. Objective: Determine efficacy and safety of BA in statin-intolerant patients receiving no background statin therapy across 4 phase 3 clinical trials. Methods: Data were pooled from 4 randomized (2:1), placebo-controlled studies evaluating oral BA 180 mg once daily vs placebo for 12 to 52 weeks. Primary efficacy endpoint was LDL-C % change from baseline to week 12. Safety assessments included treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI), and laboratory values. For patients who reported SAMs, additional information around etiology and location were collected. Results: Of 3621 patients, 586 (394 BA; 192 placebo) reported intolerance to multiple statins because of SAMS or other AEs and received no statins during the studies. Mean baseline LDL-C was 148.7 mg/dL. After 12 weeks, BA significantly lowered LDL-C vs placebo (placebo-corrected, -26.5%; P < 0.001). Myalgia was the top reason for drug discontinuation, but was less common in the BA arm (17.7%) vs placebo (43.5%). CK > 5 х ULN was uncommon in both groups. Among AESIs (Table) , muscle disorders were reported by 12.7% (BA) vs 14.1% (placebo). Myalgia was less common with BA (4.6%) vs placebo (7.3%). Muscle spasms (4.1% vs 3.6%) and pain in extremity (3.3% vs 2.1%) were comparable between treatment groups. Muscular weakness was rare (0.5% BA, 1% placebo). Conclusion: Among the population of patients unable to use statins, BA significantly lowered LDL-C vs placebo without increasing muscle-related TEAEs. BA may be an appropriate lipid-lowering therapy for patients with hyperlipidemia who are statin intolerant.

Hardships of drugs monitoring – Ambiguities in pharmacovigilance (PV) rules 2018 and guidelines 2019 in the Pakistan

2021 ◽  
Author(s):  
Nazish Abbas ◽  
Rawshan Jabeen
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Self Medication ◽  
Over The Counter ◽  
Healthcare Settings ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Pharmaceutical Industries ◽  
The Government ◽  
Very High

Introduction: Pharmacovigilance is the monitoring of drugs in and after post marketing surveillance phase of drug development and clinical trials. The phases in clinical trials is restricted to a certain population size under some conditions therefore all effects of medicine which is under trials is limited to the involved participants and it needs to be monitored through a constant channel later for eliminating the adverse events of drugs, when it is ready to be used by general consumers. In a country like Pakistan where self-medication and over the counter (OTC) medicine rate is already very high 25-75%, the regulations to control this health threat is weak due to the weak regulations. This paper is aimed to address the critical analysis on the pipeline draft of Pharmacovigilance Rules 2018 and Guidelines 2019 of Pakistan. Methodology and Rationale: The qualitative document analysis has been done by using National PV guidelines and Rules 2018 draft of Pakistan. The culture of reporting adverse events of medicines in Pakistan is not followed because of no awareness and no PV training of Pharmacists and Physicians in healthcare settings who could disseminate PV and understand the need of this hence. Pharmaceutical industries also do not adopt and accept this subject properly because of no regulations by the government and regulatory authorities. They do not have proper workforce and departments for PV.  

scholarly journals Vigilância de eventos adversos pós-vacinação e segurança de programas de imunização

2011 ◽  
Vol 45 (1) ◽  
pp. 173-184 ◽  
Author(s):  
Eliseu Alves Waldman ◽  
Karin Regina Luhm ◽  
Sandra Aparecida Moreira Gomes Monteiro ◽  
Fabiana Ramos Martin de Freitas
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Vaccine Surveillance ◽  
Phase Iv

O objetivo da revisão foi analisar aspectos conceituais e operacionais de sistemas de vigilância de eventos adversos pós-vacina. Foram incluídos artigos disponíveis em formato eletrônico, publicados entre 1985 e 2009, selecionados nas bases Medline/PubMed, com as palavras-chave: "adverse events following vaccine", "adverse events following vaccine surveillance", "post-marketing surveillance" e "safety vaccine" e "Phase IV clinical trials", e excluídos aqueles com foco em tipos específicos desses eventos. Foram apontados os principais aspectos que justificam a importância dos eventos adversos pós-vacina em saúde pública, os instrumentos que garantem a segurança das vacinas e as finalidades, atributos, tipos, interpretações de dados, limitações e novos desafios da vigilância de eventos adversos pós-vacina, bem como estratégias para aumentar sua sensibilidade. A revisão é concluída com desafios para os próximos anos, visando à segurança e confiabilidade dos programas de vacinação.

scholarly journals Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Vaccine ◽  
2019 ◽  
Vol 37 (18) ◽  
pp. 2482-2493 ◽  
Author(s):  
Marta López-Fauqued ◽  
Laura Campora ◽  
Frédérique Delannois ◽  
Mohamed El Idrissi ◽  
Lidia Oostvogels ◽  
...  
Keyword(s):  
Safety Profile ◽  
Pooled Analysis ◽  
Zoster Vaccine ◽  
Phase 3 ◽  
Recombinant Zoster Vaccine

scholarly journals Recombinant Zoster Vaccine (Shingrix) real-world effectiveness in the first two years post-licensure

2021 ◽  
Author(s):  
Hector S Izurieta ◽  
Xiyuan Wu ◽  
Richard Forshee ◽  
Yun Lu ◽  
Heng-Ming Sung ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Herpes Zoster ◽  
Real World ◽  
Postherpetic Neuralgia ◽  
Vaccine Effectiveness ◽  
Community Dwelling ◽  
Zoster Vaccine ◽  
Post Market ◽  
Recombinant Zoster Vaccine ◽  
Dose Vaccine

Abstract Background Shingrix™ (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as two doses given 2–6 months apart, among adults ages ≥50 years. Clinical trials yielded efficacy of &gt;90% for confirmed herpes zoster,but post-market vaccine performance has not been evaluated. Efficacy of a single dose, delayed second dose, or among persons with autoimmune or general immunosuppressive conditions have also not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. Methods We conducted a cohort study among vaccinated and unvaccinated Medicare Part D community dwelling beneficiaries ages &gt;65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance, and marginal structural models to estimate hazard ratios. Results We found a vaccine effectiveness of 70.1% (95% CI, 68.6–71.5) and 56.9% (95% CI, 55.0–58.8) for two and one doses, respectively. The two-dose vaccine effectiveness was not significantly lower for beneficiaries 80+ years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). Conclusions This large real-world observational study of effectiveness of Shingrix demonstrates the benefit of completing the two-dose regimen. Second doses administered beyond the recommended 6 months did not impair vaccine effectiveness.Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

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