Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.000
Filtrar
2.
Clin Drug Investig ; 41(12): 1075-1086, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34784011

RESUMO

OBJECTIVE: Since May 2018, a 6-year post­marketing surveillance (PMS) has been underway to evaluate the safety and effectiveness of letermovir for cytomegalovirus (CMV) prophylaxis in Japanese patients with allogenic hematopoietic stem-cell transplantation (allo-HSCT). The interim PMS data for 461 patients collected as of March 2021 are reported in this publication. METHODS: The case report forms (CRFs) were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) using data elements in the Transplant Registry Unified Management Program (TRUMP) and sent to individual HSCT centers to decrease burden of reporting. These CRFs were completed by physicians in the respective HSCT centers and sent to MSD K.K., Tokyo, Japan. RESULTS: Allo-HSCT recipients prescribed with letermovir for CMV prophylaxis were included across 136 centers in Japan between May 2018 and March 2021. Safety and effectiveness were assessed for 460 and 373 patients, respectively. Of the patients in the safety analysis, 13.9 % experienced adverse drug reactions, the most frequent of which were renal impairment (2.2 %) and nausea (1.7 %). Among patients in the effectiveness analysis, the overall CMV antigen positivity rate was 21.2 % at Week 14 and 37.5 % at Week 24 after allo-HSCT. CONCLUSIONS: Interim data from this largest of real-world studies confirm the safety and effectiveness of letermovir for CMV prophylaxis in Japanese allo-HSCT recipients. Given the limited data on Asian patients for letermovir use, this survey will provide valuable information for medical decision-making in routine clinical practice, serving as a vital supplement to the results obtained from clinical trials.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Acetatos , Antivirais/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Japão , Vigilância de Produtos Comercializados , Quinazolinas
3.
JAMA ; 326(16): 1606-1613, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34617967

RESUMO

Importance: As part of postauthorization safety surveillance, the US Food and Drug Administration (FDA) has identified a potential safety concern for Guillain-Barré syndrome (GBS) following receipt of the Ad26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccine. Objective: To assess reports of GBS received in the Vaccine Adverse Event Reporting System (VAERS) following Ad26.COV2.S vaccination. Design, Setting, and Participants: Reports of presumptive GBS were identified in a US passive reporting system (VAERS) February-July 2021 and characterized, including demographics, clinical characteristics, and relevant medical history. Exposures: Receipt of the Ad26.COV2.S vaccine; the comparator was the background rate of GBS in the general (unvaccinated) population that had been estimated and published based on a standardized case definition. Main Outcomes and Measures: Presumptive GBS; the reporting rate was analyzed, including calculation of the observed to expected ratio based on background rates and vaccine administration data. Because of limited availability of medical records, cases were not assessed according to the Brighton Collaboration criteria for GBS. Results: As of July 24, 2021, 130 reports of presumptive GBS were identified in VAERS following Ad26.COV2.S vaccination (median age, 56 years; IQR, 45-62 years; 111 individuals [86.0%] were < 65 years; 77 men [59.7%]). The median time to onset of GBS following vaccination was 13 days (IQR, 10-18 days), with 105 cases (81.4%) beginning within 21 days and 123 (95.3%) within 42 days. One hundred twenty-one reports (93.1%) were serious, including 1 death. With approximately 13 209 858 doses of vaccine administered to adults in the US, the estimated crude reporting rate was 1 case of GBS per 100 000 doses administered. The overall estimated observed to expected rate ratio was 4.18 (95% CI, 3.47-4.98) for the 42-day window, and in the worst-case scenario analysis for adults 18 years or older, corresponded to an estimated absolute rate increase of 6.36 per 100 000 person-years (based on a rate of approximately 8.36 cases per 100 000 person-years [123 cases per 1 472 162 person-years] compared with a background rate of approximately 2 cases per 100 000 person-years). For both risk windows, the observed to expected rate ratio was elevated in all age groups except individuals aged 18 through 29 years. Conclusions and Relevance: These findings suggest a potential small but statistically significant safety concern for Guillain-Barré syndrome following receipt of the Ad26.COV2.S vaccine. However, the findings are subject to the limitations of passive reporting systems and presumptive case definition, and they must be considered preliminary pending analysis of medical records to establish a definitive diagnosis.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/epidemiologia , Adulto , Distribuição por Idade , Idoso , Vacinas contra COVID-19/administração & dosagem , Feminino , Síndrome de Guillain-Barré/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Vigilância de Produtos Comercializados , Estados Unidos/epidemiologia , Vacinação/estatística & dados numéricos , Adulto Jovem
4.
AMA J Ethics ; 23(9): E673-678, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710025

RESUMO

The number of new medical devices cleared by the US Food and Drug Administration (FDA) through the 510(k) pathway that has subsequently been associated with safety risks has led to discussion of approaches to regulation and communication of device risks. As debate continues over whether the pathway needs to be altered, features of ethical use of 510(k)-cleared devices can include (1) heightened caution with respect to newly cleared 510(k) products until adequate data are gathered through postmarket surveillance, (2) facilitating informed consent by improving physician and patient knowledge of the 510(k) pathway, and (3) basing distribution of these devices on individual risk assessments while ensuring equitable access.


Assuntos
Aprovação de Equipamentos , Vigilância de Produtos Comercializados , Comunicação , Humanos , Medição de Risco , Estados Unidos , United States Food and Drug Administration
5.
Korean J Gastroenterol ; 78(4): 219-226, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697276

RESUMO

Background/Aims: Constipation is a common gastrointestinal disorder. Prucalopride is a dihydrobenzofurancarboxamide derivative with gastrointestinal prokinetic activities and is recommended as an appropriate choice in patients unresponsive to laxatives. This study assessed the safety and efficacy of prucalopride in Korean patients with chronic constipation, in whom laxatives were ineffective. Methods: This prospective, non-interventional post-marketing surveillance of prucalopride was conducted from 2012 to 2018 at 28 hospitals in Korea. Adults who received prucalopride for the symptomatic treatment of chronic constipation were included. The patients received 2 mg of prucalopride once daily or 1 mg once daily in patients older than 65 years. The baseline characteristics, adverse events (AEs), and seven-point scale of Clinical Global Impression-Improvement were collected. Results: Of 601 patients, 67.7% were female, and the mean age was 62.3 years. Three hundred patients (49.9%) were older than 65 years. At the baseline, 70.0% of patients reported less than two instances of spontaneous complete bowel movements per week. AEs were reported in 107 patients (17.7%), including headache (3.2%) and diarrhea (2.8%). Seven serious AEs (SAEs) were reported in five patients (0.8%). The SAEs were resolved without complications; there were no cases of death. All SAEs were assessed as 'unlikely' causality with prucalopride. In 72.7% of patients, chronic constipation was improved by the prucalopride treatment during the study period. Conclusions: This study demonstrated the promising safety and efficacy profile of prucalopride in clinical practice. Thus, prucalopride should be considered in patients with chronic constipation when bowel symptoms are refractory to simple laxatives.


Assuntos
Constipação Intestinal , Laxantes , Adulto , Benzofuranos , Doença Crônica , Constipação Intestinal/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Laxantes/uso terapêutico , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Prospectivos , República da Coreia , Resultado do Tratamento
6.
MMWR Morb Mortal Wkly Rep ; 70(39): 1379-1384, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34591835

RESUMO

On August 12, 2021, the Food and Drug Administration (FDA) amended Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech and Moderna COVID-19 vaccines to authorize administration of an additional dose after completion of a primary vaccination series to eligible persons with moderate to severe immunocompromising conditions (1,2). On September 22, 2021, FDA authorized an additional dose of Pfizer-BioNTech vaccine ≥6 months after completion of the primary series among persons aged ≥65 years, at high risk for severe COVID-19, or whose occupational or institutional exposure puts them at high risk for COVID-19 (1). Results from a phase 3 clinical trial conducted by Pfizer-BioNTech that included 306 persons aged 18-55 years showed that adverse reactions after receipt of a third dose administered 5-8 months after completion of a 2-dose primary mRNA vaccination series were similar to those reported after receipt of dose 2; these adverse reactions included mild to moderate injection site and systemic reactions (3). CDC developed v-safe, a voluntary, smartphone-based safety surveillance system, to provide information on adverse reactions after COVID-19 vaccination. Coincident with authorization of an additional dose for persons with immunocompromising conditions, the v-safe platform was updated to allow registrants to enter information about additional doses of COVID-19 vaccine received. During August 12-September 19, 2021, a total of 22,191 v-safe registrants reported receipt of an additional dose of COVID-19 vaccine. Most (97.6%) reported a primary 2-dose mRNA vaccination series followed by a third dose of the same vaccine. Among those who completed a health check-in survey for all 3 doses (12,591; 58.1%), 79.4% and 74.1% reported local or systemic reactions, respectively, after dose 3, compared with 77.6% and 76.5% who reported local or systemic reactions, respectively, after dose 2. These initial findings indicate no unexpected patterns of adverse reactions after an additional dose of COVID-19 vaccine; most of these adverse reactions were mild or moderate. CDC will continue to monitor vaccine safety, including the safety of additional doses of COVID-19 vaccine, and provide data to guide vaccine recommendations and protect public health.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Vigilância de Produtos Comercializados , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Adulto Jovem
7.
JAMA ; 326(5): 420-432, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342614

RESUMO

Importance: US law generally requires testing of high-risk medical devices prior to approval, as well as premarket evaluation of moderate-risk medical devices, with the goal of ensuring that the benefits of these products exceed their risks. The US Food and Drug Administration (FDA) attempts to balance the need for evidence generation with an approval process that facilitates access and encourages innovation. Objective: To review the development of laws and standards affecting the evaluation and oversight of medical devices by the US regulatory system and the outcomes of this system from 1976 to 2020. Evidence Review: Laws enacted by US Congress and regulations promulgated by the FDA through 2020; databases maintained by the FDA of device authorizations from 1976 to 2020; and annual reports of user fees paid to the FDA by industry. Findings: Since Congress and the FDA initiated premarket review of medical devices in 1976, some fundamental innovations in the device regulation system have included special pathways to accelerate availability of investigational devices, more flexible evidence and review requirements, and increased funding to the FDA through industry-paid user fees. From 1987 to 2020, the annual number of novel devices granted premarket approval (which excludes supplements) ranged from 8 to 56 (median, 32), and the number of clearances for 510(k) devices (those that are "substantially equivalent" to marketed devices) ranged from 2804 to 5762 (median, 3404). User fee funding for devices was established in 2002 and annual fees collected increased from $30 million in 2003 (in 2019 dollars) to more than $208 million in 2019; this represented 43% of FDA funding related to the review of medical devices. Although many new devices have led to considerable patient benefit, such as hypodermic needles and magnetic resonance imaging machines, important adverse events caused by some devices, such as an implanted device for birth control and a surgical mesh implant for pelvic organ prolapse, have led to calls to reexamine the regulatory system for such products. Conclusions and Relevance: Over the last 45 years, medical device regulation has become more complex, with more regulatory pathways and greater variations in the evidence and controls required for authorization. Increased FDA support from industry and concern about flexible authorization requirements reflect the tension between efficient access and the need for assurances that products will safely benefit patients.


Assuntos
Aprovação de Equipamentos/legislação & jurisprudência , Regulamentação Governamental/história , História do Século XX , História do Século XXI , Legislação Médica/história , Legislação Médica/tendências , Patentes como Assunto/história , Patentes como Assunto/legislação & jurisprudência , Vigilância de Produtos Comercializados , Software/história , Software/legislação & jurisprudência , Estados Unidos , United States Food and Drug Administration/história
8.
Adv Ther ; 38(9): 4949-4960, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34386895

RESUMO

INTRODUCTION: Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking. METHODS: This was a post-marketing surveillance study that included all Japanese patients who received thyrotropin alfa, either as a supporting diagnostic from January 2009 to December 2016, or as adjunctive treatment for ablation from May 2012 to October 2018. Information was collected on patient demographics, thyroid cancer characteristics, adverse drug reactions (ADRs), scintigraphy, serum thyroglobulin (Tg) testing, and hypothyroidism symptoms. RESULTS: A total of 9268 patients were included in the safety analysis and 9031 in the effectiveness analysis. In the safety analysis set, 3444 patients received thyrotropin alfa as a diagnostic and 5822 received it as treatment. ADRs occurred in 7.1% (n = 660) of patients, including 9.4% (n = 324) of patients who received thyrotropin alfa as a diagnostic and 5.8% (n = 336) of patients who received it as treatment. Nausea was the most common ADR (4.0% of overall safety population). Among patients who received thyrotropin alfa as a diagnostic (n = 1835), the Tg test was positive in 53.6% after the second dose. The scintigram was rated as "readable" in 3023 of the 3054 patients included in this analysis (99.0%). Of the 765 patients who were included in the assessment of response to ablation at 6 months to 1 year after the procedure, 621 (81.2%) were considered to have had "treatment success". There were no significant differences in the proportions of patients who had hypothyroidism symptoms before the first and after the second dose of thyrotropin alfa. CONCLUSION: In this large post-marketing surveillance study, thyrotropin alfa was well tolerated and showed effectiveness that was comparable to that observed in randomised, controlled trials.


Assuntos
Neoplasias da Glândula Tireoide , Tirotropina Alfa , Humanos , Radioisótopos do Iodo , Japão , Vigilância de Produtos Comercializados , Proteínas Recombinantes , Tireoglobulina , Tireotropina
9.
J Manag Care Spec Pharm ; 27(10): 1503-1508, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34459234

RESUMO

With the dual goals of identifying key actions that can support the further development and use of biosimilars in the United States and providing consistent and accurate messages about the value of biosimilars, AMCP held a virtual multidisciplinary stakeholder forum December 15-16, 2020. The participants, including payers, pharmacists, integrated delivery system leaders, health economists and analysts, academicians, patient advocates, pharmaceutical manufacturers, and other key decision makers, spent the 2 days (1) identifying challenges with biosimilar adoption within the US health care system; (2) determining clear and unbiased scientific messaging to support broader acceptance of biologics as valid therapeutic options and to facilitate faster time to biosimilar adoption; and (3) discussing needs and opportunities related to real-world evidence to help with adoption of biosimilars. Participants identified various challenges, including approval-related nuances and other regulatory considerations; general information about biosimilars and lack of consistent, positive messaging; clinical and administrative barriers; and economic complexities and variation. They also highlighted areas of opportunity, such as demystifying information and developing strong, positive messaging around biologics and biosimilars, and improving confidence in biosimilars by using tools such as education and real-world evidence, organizational strategies to ease biosimilar adoption, and updates to legislation and regulation to reduce barriers related to biosimilars. DISCLOSURES: This forum was sponsored by Amgen, the Association for Accessible Medicines, Boehringer Ingelheim, Fresenius Kabi, Johnson & Johnson, Novo Nordisk, Pfizer, Sandoz, and Takeda. These proceedings were prepared as a summary of the forum to represent common themes; they are not necessarily endorsed by all attendees, nor should they be construed as reflecting group consensus.


Assuntos
Medicamentos Biossimilares , Cobertura do Seguro , Seguro de Serviços Farmacêuticos , Vigilância de Produtos Comercializados , Medicamentos Biossimilares/uso terapêutico , Prestação Integrada de Cuidados de Saúde , Política de Saúde , Humanos , Estados Unidos , United States Food and Drug Administration
10.
Methods Inf Med ; 60(3-04): 116-122, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34450668

RESUMO

BACKGROUND: The European Medical Device Regulation 2017/745 (MDR) has its date of application in May 2021. This new legislation has refined and expanded the need of manufacturers to have a postmarket surveillance (PMS) system. According to this legislation, a postmarket clinical follow-up (PMCF) plan is also required. Manufacturers of high-risk medical devices are obliged to conduct both PMCF and PMS studies. There is thus the need to generate evidence from clinical data. OBJECTIVES: The conduct of several studies for PMS and PMCF can be cumbersome. We therefore aim to present a modular approach to combine PMS and PMCF studies into a single study. MATERIALS AND METHODS: We extracted the topics listed in the MDR, especially Annex XV, Section 3, the Good Clinical Practice for medical devices (EN 14155:2020, Annex A). In addition, we added topics according to the SPIRIT and the SPIRIT-PRO statement and created a draft clinical investigation plan (CIP). RESULTS: The CIP template is provided as part of the manuscript. The modular concept has passed the required regulatory and legal requirements for one specific study. CONCLUSION: A modular approach for combining PMCF and PMS studies in a single CIP has been developed and implemented, and it is ready for use. The provided CIP template should enable other researchers and groups to adopt this concept according to their needs.


Assuntos
Aprovação de Equipamentos , Vigilância de Produtos Comercializados , Seguimentos , Estados Unidos , United States Food and Drug Administration
11.
Cancer Sci ; 112(11): 4692-4701, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34431585

RESUMO

Postmarketing surveillance of Japanese patients with unresectable, previously treated, advanced or recurrent non-small-cell lung cancer treated with nivolumab was undertaken during the conditional approval period. The study aim was to evaluate the occurrence of treatment-related adverse events of nivolumab in the real world. Patients were registered between December 2015 and March 2016 at 536 sites. Nivolumab was given intravenously (3 mg/kg every 2 weeks); the observation period was 12 months after the first dose of nivolumab. Patients were evaluated for safety (n = 3601; 18.2% ≥75 years, 22.4% ECOG performance status ≥2) and effectiveness (n = 3570). The frequencies of any grade and grade 3 or higher treatment-related adverse events were 47.1% and 15.9%, respectively. The most frequent treatment-related adverse events (any grade) were interstitial lung disease (6.4%), hypothyroidism (5.7%), and diarrhea (4.4%). Treatment-related adverse events of special interest (priority items) occurring at a frequency of 5% or more were adverse events related to interstitial lung disease, thyroid dysfunction, liver dysfunction, colitis/severe diarrhea, infusion reaction, and infusion reaction within 24 hours. Significant risk factors for these priority items were identified by competing risk analysis: interstitial lung disease (previous/comorbid interstitial lung disease, abnormal findings on chest imaging, and smoking history); liver dysfunction (previous/comorbid liver disease, smoking history, and metastasis); thyroid dysfunction (previous/comorbid thyroid disease and performance status); and colitis/severe diarrhea (treatment line 2 vs ≥3). The 12-month survival rate was 40.7%. In conclusion, the safety profile of nivolumab in this postmarketing surveillance was similar to that in clinical trials, and no new safety signals were identified. The study was registered with the Japan Pharmaceutical Information Center (clinicaltrials.jp: Japic-163271).


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/efeitos adversos , Vigilância de Produtos Comercializados , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Diarreia/induzido quimicamente , Esquema de Medicação , Feminino , Humanos , Hipotireoidismo/induzido quimicamente , Japão , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Taxa de Sobrevida
12.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444905

RESUMO

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.


Assuntos
Anti-Hipertensivos/uso terapêutico , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/uso terapêutico , Vigilância de Produtos Comercializados , Ácido gama-Aminobutírico/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Cães , Feminino , Fermentação , Humanos , Masculino , Leite/química , Gravidez , Ratos , Alimentos de Soja/análise , Estados Unidos
13.
PLoS One ; 16(7): e0253513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329291

RESUMO

A post-marketing study was performed on all patients who had started treatment with iguratimod, a conventional synthetic disease-modifying antirheumatic drug approved in Japan. During the study period, various safety measures were implemented to reduce risks. We investigated the frequency of adverse drug reactions before and after implementation of each safety measure to examine the preventive effect of these measures. Post-hoc analysis was performed using data from all-case surveillance of iguratimod. The subjects were all of the patients receiving iguratimod for whom safety information was obtained. To identify the time after starting administration when adverse drug reactions were most likely to occur, a generalized linear mixed-effect model was applied for the period from initiation of administration until occurrence of reactions in each patient. The mean incidence of adverse drug reactions per patient was compared before and after the implementation of safety measures by using generalized estimating equations based on a two-sided test, 95% confidence interval, and 5% significance level. The number of patients treated with iguratimod was not related to changes in the number of patients with adverse drug reactions. After implementing precautions regarding co-administration with warfarin and liver dysfunction, the estimated mean incidence rate of adverse drug reactions (95% confidence interval) decreased significantly to 0.73 (0.59-0.90) and 0.72 (0.55-0.94), respectively. Accordingly, some of the implementation of safety measures significantly reduced adverse drug reactions. The effectiveness of safety measures implemented during the all-case surveillance of iguratimod was evaluated, revealing that early implementation of safety measures decreased the incidence of adverse drug reactions.


Assuntos
Artrite Reumatoide , Cromonas , Modelos Biológicos , Sulfonamidas , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Cromonas/administração & dosagem , Cromonas/efeitos adversos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Prospectivos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
14.
Clin Pharmacol Ther ; 110(6): 1537-1546, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34314511

RESUMO

This study aimed to systematically investigate if any of the available drugs in the electronic health record (EHR) can be repurposed as potential treatment for coronavirus disease 2019 (COVID-19). Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on 9,748 patients with COVID-19 at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID-19 disease outcomes. Patient exposure to a drug between 3-months prior to the pandemic and the COVID-19 diagnosis was chosen as the exposure of interest. All-cause of death was selected as the primary outcome. Hospitalization, admission to the intensive care unit, and need for mechanical ventilation were identified as secondary outcomes. Overall, 17 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to two types of 13-valent pneumococcal conjugate vaccines, PCV13 (odds ratio (OR), 0.31, 95% confidence interval (CI), 0.12-0.81 and OR, 0.33, 95% CI, 0.15-0.73), diphtheria toxoid and tetanus toxoid vaccine (OR, 0.38, 95% CI, 0.15-0.93) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID-19 outcomes: acellular pertussis vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), flaxseed extract, ethinyl estradiol, estradiol, turmeric extract, ubidecarenone, azelastine, pseudoephedrine, dextromethorphan, omega-3 fatty acids, fluticasone, and ibuprofen. In conclusion, this cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID-19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs.


Assuntos
COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Vacinas Pneumocócicas/administração & dosagem , Vigilância de Produtos Comercializados/métodos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Estudos de Coortes , Humanos , Estudos Retrospectivos
15.
J Eur Acad Dermatol Venereol ; 35(11): 2277-2284, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34320249

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal and anogenital regions. Overall prevalence of HS is ˜1%, and the impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high. OBJECTIVES: To estimate the real-world effectiveness of adalimumab (Humira®) treatment in patients with moderate-to-severe HS on disease severity, pain, QoL, work productivity and HRU. METHODS: HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patients - a Multi-cOuNtry studY in Real Life Setting) is a multicentre, postmarketing observational study in adult patients with moderate-to-severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36 and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using as-observed data. RESULTS: The proportion of patients reaching the primary HiSCR endpoint was 70.2% (n = 132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P < 0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P < 0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P < 0.05), and there was a ˜50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated. CONCLUSIONS: In this real-world setting, adalimumab treatment of moderate-to-severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.


Assuntos
Hidradenite Supurativa , Qualidade de Vida , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Hidradenite Supurativa/tratamento farmacológico , Humanos , Vigilância de Produtos Comercializados , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Sci Rep ; 11(1): 14022, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234253

RESUMO

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , COVID-19/tratamento farmacológico , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Vigilância de Produtos Comercializados , Segurança
17.
Expert Opin Drug Saf ; 20(11): 1421-1431, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34280062

RESUMO

BackgroundTo investigate the adverse event (AE) profile of tedizolid and linezolid in post-marketing surveillance.Research design and methodsWe queried the worldwide FDA Adverse Event Reporting System and selected all records where tedizolid and linezolid were reported as suspect by removing potential duplicates. Disproportionality analysis was performed investigating designated medical events (DMEs) and specific AEs of clinical interest reported with tedizolid. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL95%CI)>1, using linezolid as comparator. Case-by-case assessment of AEs reported in at least three cases with tedizolid was performed.ResultsOverall, 271 and 11,259 reports mentioning respectively tedizolid and linezolid were recorded, of which respectively 59 and 4,473 patients with DMEs or selected AEs were found. No difference emerged for the selected AEs except for increased reporting of hepatic failure (N = 3; LL95%CI = 1.06) with tedizolid considering reports collected after 2014. Extensive off-label use in terms of therapeutic indications (83.6%) and treatment duration was reported with tedizolid.ConclusionsSimilar AE reporting between the two oxazolidinones was found. Considering limitations of pharmacovigilance, this hypothesis of comparable safety profile should be tested prospectively through dedicated real-world studies.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antibacterianos/efeitos adversos , Linezolida/efeitos adversos , Oxazolidinonas/efeitos adversos , Tetrazóis/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Vigilância de Produtos Comercializados , Estados Unidos , United States Food and Drug Administration
18.
Adv Ther ; 38(8): 4480-4504, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34275116

RESUMO

INTRODUCTION: Dolutegravir (DTG), a novel HIV-integrase strand transfer inhibitor (INSTI), is usually used with multiple antiretrovirals (ARVs) for treatment of HIV. DTG is now approved as Tivicay tablets in over 120 countries and Triumeq combination tablets (DTG/abacavir [ABC]/lamivudine [3TC]) in over 90 countries. In Japan, these formulations have been marketed since 2014 and 2015. The post-marketing prospective surveillance has been conducted as part of the HIV-Related Drug (HRD) cooperative survey aimed to collect actual drug use information in all of these DTG-treated patients in accordance with conditions for initial approvals. METHODS: The survey has been conducted to evaluate long-term safety and effectiveness of DTG since 2014, for approximately 6 years. The safety was evaluated by incidence of adverse drug reactions (ADRs) and change in body weight. The effectiveness was evaluated by plasma HIV RNA copies/mL and peripheral CD4+ cell counts. RESULTS: Of 2292 patients in 30 Japanese sites, 565 (24.65%) reported ADRs. The most common ADR was blood creatinine increased (4.28%). Incidence of ADRs was statistically significantly higher in patients with severe symptoms (Centers for Disease Control and Prevention [CDC] categories B and C) than those with category A, and in patients with comorbidities than those without comorbidities. Whereas incidence of ADRs was statistically significantly lower in antiretroviral therapy (ART)-experienced patients than that in ART-naïve patients. Incidence of ADRs related to suicide or self-injurious behavior was statistically significantly higher in patients with comorbidities of psychiatric disorders than those without comorbidities. The body weight tended to increase over time and those changes and percentage changes from baseline were greater in ART-naïve patients compared with ART-experienced patients. HIV RNA copies/mL and CD4+ cell counts showed favorable shifts from baseline in both ART-naïve and ART-experienced patients. CONCLUSION: The results of the survey identified no new safety and effectiveness risks in Japanese patients with HIV/AIDS treated with DTG.


Assuntos
Fármacos Anti-HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Humanos , Japão/epidemiologia , Marketing , Oxazinas , Piperazinas , Vigilância de Produtos Comercializados , Estudos Prospectivos , Piridonas
19.
J Infect Chemother ; 27(10): 1436-1446, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34226112

RESUMO

INTRODUCTION: We conducted a post-marketing surveillance of laninamivir octanoate hydrate for Inhalation Suspension Set in patients under the age of 5 infected with the influenza virus to evaluate safety and efficacy of the drug. METHODS: Subjects enrolled by the centralized enrollment system were administered laninamivir once using a nebulizer based on the package insert. RESULTS: Safety was evaluated in 1104 patients. The incidence of ADRs was 1.00% (11/1104). Compared to the incidence of ADRs of 2.04% (9/441) in the clinical trials for development, no increase in the frequency of ADRs was noted. Serious ADRs were noted in 3 patients (5 cases): 2 cases of convulsive attack, each 1 case of muscular weakness, a depressed level of consciousness, and pain in extremities. Excluding 2 patients with unknown outcomes, all of the patients recovered or their symptoms were alleviated. To detect risk factors for the occurrence of ADRs, 16 attributes were examined, and none of them were found to be significant. Efficacy was evaluated in 881 patients. The median time (95% CI) to fever resolution was 37.0 (33.0-39.0) h in type A virus (785 patients), 45.0 (34.0-56.0) h in type B virus (95 patients), and 22.0 h (1 patient) in the mixed type. This was similar to the time to fever resolution in the clinical trials. CONCLUSION: The results of this surveillance verified that there are no noticeable problems with the safety or efficacy of laninamivir for children under the age of 5 infected with the influenza A and B viruses.


Assuntos
Influenza Humana , Neuraminidase , Administração por Inalação , Antivirais/efeitos adversos , Pré-Escolar , Guanidinas/uso terapêutico , Humanos , Influenza Humana/tratamento farmacológico , Vigilância de Produtos Comercializados , Piranos/uso terapêutico , Ácidos Siálicos/uso terapêutico , Zanamivir/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...