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1.
BMC Cancer ; 21(1): 1021, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521387

RESUMO

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48-11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indazóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , África do Norte , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Ásia , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Neoplasias Renais/etnologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Oriente Médio , Intervalo Livre de Progressão , Estudos Prospectivos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Fatores de Risco , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
2.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356673

RESUMO

Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition of COX-2 in healthy tissues, has considerably limited their use in clinic. In addition, increasing evidence indicate that these anti-cancerous properties are not strictly dependent on the inhibition of the catalytic site. These findings have led to the development of non-active COX-2 inhibitors analogues aiming at preserving the antitumor effects of COX-2 inhibitors without their side effects. Among them, two celecoxib derivatives, 2,5-Dimethyl-Celecoxib and OSU-03012, have been developed and suggested for the treatment of viral (e.g., recently SARS-CoV-2), inflammatory, metabolic diseases and cancers. These molecules display stronger anti-tumor properties than celecoxib and thus may represent promising anti-cancer molecules. In this review, we discuss the impact of these two analogues on cancerous processes but also their potential for cancer treatment alone or in combination with existing approaches.


Assuntos
Antineoplásicos/uso terapêutico , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Neoplasias/tratamento farmacológico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/farmacologia , Celecoxib/efeitos adversos , Celecoxib/análogos & derivados , Celecoxib/farmacologia , Ciclo Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Humanos , Pirazóis/efeitos adversos , Pirazóis/química , Pirazóis/farmacologia , Sulfonamidas/efeitos adversos , Sulfonamidas/química , Sulfonamidas/farmacologia
3.
Am J Clin Dermatol ; 22(5): 693-707, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34406619

RESUMO

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.


Assuntos
Dermatite Atópica/tratamento farmacológico , Infecções/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Sulfonamidas/efeitos adversos , Acne Vulgar/induzido quimicamente , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Cefaleia/induzido quimicamente , Herpes Simples/epidemiologia , Herpes Zoster/epidemiologia , Humanos , Incidência , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Contagem de Plaquetas , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Fatores de Risco , Sulfonamidas/administração & dosagem , Fatores de Tempo , Tromboembolia Venosa/epidemiologia , Adulto Jovem
4.
J Med Case Rep ; 15(1): 355, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284818

RESUMO

BACKGROUND: Cystoid macular edema is a rare, vision-threatening side effect of the taxane family of anticancer agents. There is no established treatment or standard treatment protocol for taxane-related cystoid macular edema. Here, we report two cases of taxane-related cystoid macular edema that were treated with topical dorzolamide. CASE PRESENTATION: In case 1, a 72-year-old Japanese woman with bilateral geographic choroiditis reported for a follow-up visit with a complaint of blurred vision in both eyes for 2 months after starting nanoparticle albumin-bound paclitaxel chemotherapy for multiple metastases of her breast cancer. Her best-corrected visual acuity had dropped from 1.2 to 0.9 in the right eye and from 1.0 to 0.4 in the left eye. Fundus examination showed no newly active geographic choroiditis lesion, but optical coherence tomography exhibited cystoid macular edema. We suspected taxane-related cystoid macular edema and terminated nanoparticle albumin-bound paclitaxel, and started topical dorzolamide treatment. Cystoid macular edema nearly resolved within 6 weeks in the right eye and within 10 weeks in the left eye after starting topical dorzolamide treatment. The resolution of cystoid macular edema without leaving a chorioretinal scar after discontinuation of paclitaxel confirmed our initial diagnosis of taxane-related cystoid macular edema. A few inconspicuous cystoid spaces persisted at the parafovea for a year after dorzolamide treatment ended, but regressed after restarting dorzolamide treatment without any side effects. Best-corrected visual acuity improved to 1.2 in the right eye and 1.0 in the left eye. In case 2, a 70-year-old Japanese man, who received nanoparticle albumin-bound paclitaxel for pancreatic cancer with multiple metastases, developed bilateral cystoid macular edema. Best-corrected visual acuity was 0.3 bilaterally. Cystoid macular edema resolved within 5 weeks after stopping nanoparticle albumin-bound paclitaxel and starting topical dorzolamide treatment confirming the diagnosis of taxane-related cystoid macular edema. Nine weeks later, best-corrected visual acuity improved to 0.8 in the right eye and 1.0 in the left eye. CONCLUSIONS: Cystoid macular edema in each case resolved within a few months without any side effects using topical dorzolamide and terminating taxane-based chemotherapy. Topical dorzolamide appears to be a safe and effective treatment option for patients with taxane-related cystoid macular edema whose quality of life is threatened by visual disturbances.


Assuntos
Edema Macular , Idoso , Feminino , Humanos , Edema Macular/induzido quimicamente , Edema Macular/tratamento farmacológico , Masculino , Qualidade de Vida , Sulfonamidas/efeitos adversos , Taxoides , Tiofenos , Tomografia de Coerência Óptica
5.
Biomolecules ; 11(7)2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202146

RESUMO

Liver malignant tumors (LMTs) represent a serious adverse drug event associated with drug-induced liver injury. Increases in endocrine-disrupting chemicals (EDCs) have attracted attention in recent years, due to their liver function-inhibiting abilities. Exposure to EDCs can induce nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which are major etiologies of LMTs, through interaction with nuclear receptors (NR) and stress response pathways (SRs). Therefore, exposure to potential EDC drugs could be associated with drug-induced LMTs. However, the drug classes associated with LMTs and the molecular initiating events (MIEs) that are specific to these drugs are not well understood. In this study, using the Food and Drug Administration Adverse Event Reporting System, we detected LMT-inducing drug signals based on adjusted odds ratios. Furthermore, based on the hypothesis that drug-induced LMTs are triggered by NR and SR modulation of potential EDCs, we used the quantitative structure-activity relationship platform for toxicity prediction to identify potential MIEs that are specific to LMT-inducing drug classes. Events related to cell proliferation and apoptosis, DNA damage, and lipid accumulation were identified as potential MIEs, and their relevance to LMTs was supported by the literature. The findings of this study may contribute to drug development and research, as well as regulatory decision making.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Neoplasias Hepáticas/epidemiologia , United States Food and Drug Administration/estatística & dados numéricos , Carbamatos/efeitos adversos , Carbamatos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/genética , Previsões , Humanos , Imidazóis/efeitos adversos , Imidazóis/toxicidade , Isoquinolinas/efeitos adversos , Isoquinolinas/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/toxicidade , Pirrolidinas/efeitos adversos , Pirrolidinas/toxicidade , Receptores de Calcitriol/genética , Receptores de Estrogênio/genética , Sulfonamidas/efeitos adversos , Sulfonamidas/toxicidade , Estados Unidos/epidemiologia , Valina/efeitos adversos , Valina/análogos & derivados , Valina/toxicidade
6.
Middle East Afr J Ophthalmol ; 28(1): 51-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321822

RESUMO

Tamsulosin is an antagonist of a subtype-specific alpha-1A- and alpha-1D-adrenoceptor (AR) that is expressed in the prostate gland, urethra, and bladder. Several reports have shown a possible relationship between ophthalmologic adverse effects and the use of alpha-1-receptor medicines, including tamsulosin. This descriptive review evaluates the intraoperative floppy iris syndrome (IFIS) associated with tamsulosin. A search of the Medline and PubMed databases was conducted to identify control trials, case reports, and observational examinations published in English. The publication dates were restricted (January 1, 2000, to January 1, 2020). Keywords (tamsulosin, alpha-blocker, ocular, eye, adverse reaction, and IFIS) were used in the searches. The searches identified 66 studies including in vitro or in vivo studies, trials, and observational studies. Twenty-two (33.33%) studies were articles citing tamsulosin and IFIS as having confirmed potential risk to ocular safety. The results of this review, including a comprehensive summary of published research on tamsulosin use in different populations, have identified several articles showing associations between tamsulosin and IFIS that merit further investigation. Suspending of potential causative pharmacological treatment of IFIS before ocular surgery including tamsulosin, proper identification of at-risk patients, preoperative prophylaxis treatments, and surgical technique modifications clearly can mitigate the anticipated risk of IFIS induced by tamsulosin.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Doenças da Íris , Tansulosina , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Humanos , Complicações Intraoperatórias/induzido quimicamente , Iris , Doenças da Íris/induzido quimicamente , Doenças da Íris/prevenção & controle , Fatores de Risco , Sulfonamidas/efeitos adversos , Tansulosina/efeitos adversos
7.
J Am Geriatr Soc ; 69(10): 2752-2758, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34235720

RESUMO

BACKGROUND: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. METHODS: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09-0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03-0.64; p = 0.011). CONCLUSIONS: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.


Assuntos
Azetidinas , COVID-19 , Pneumonia Viral , Purinas , Pirazóis , Sulfonamidas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/fisiopatologia , Feminino , Mortalidade Hospitalar , Humanos , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/efeitos adversos , Masculino , Mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Purinas/administração & dosagem , Purinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Espanha/epidemiologia , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
8.
Cancer Sci ; 112(9): 3636-3644, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34185931

RESUMO

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m2 for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Decitabina/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/cirurgia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Sulfonamidas/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Decitabina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Recidiva , Sulfonamidas/administração & dosagem , Transplante Homólogo/efeitos adversos , Adulto Jovem
9.
Andrologia ; 53(9): e14166, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34189764

RESUMO

We conducted a systematic review and meta-analysis to assess the outcomes and complications of naftopidil in treating elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and compared them with those administered with tamsulosin. A literature review was performed to identify the available randomised controlled trials concerning the comparison between naftopidil and tamsulosin for men with LUTS/BPH. We searched the following databases: the Cochrane Library Database, PubMed, Embase and Web of Science. Eleven publications involving 1,114 men (557 in the naf group and 557 in the tam group) were pooled in our analysis. We found no significant differences in the total IPSS, IPSS storage score, IPSS voiding score, quality of life index, peak urinary flow rate, average flow rate and post-void residual volumes. We assessed cardiovascular and sexual adverse events, acute urinary retention, surgical intervention, withdrawals due to any reason and withdrawals due to adverse events. The incidence of adverse events was similar among patients in naf and tam groups. In conclusion, naftopidil shared comparable efficacy and similar incidence of adverse events with tamsulosin and appears to be a promising agent for and alternative to tam. However, more prospective trials with high quality and long-term treatment duration are needed to verify this observation.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Idoso , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Naftalenos , Piperazinas , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Tansulosina/uso terapêutico , Resultado do Tratamento
10.
Am J Hematol ; 96(9): 1131-1136, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34115387

RESUMO

Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM, particularly those harboring t(11;14). We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December, 2016 and March, 2019. The data cut-off date was August 06, 2020. We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was six (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n = 31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p = 0.019) and OS (median not reached vs. 10.8 9 months, p = 0.015). Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly the t(11;14) patient-population.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Sulfonamidas/efeitos adversos , Resultado do Tratamento
11.
BMC Vet Res ; 17(1): 205, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082759

RESUMO

BACKGROUND: Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. RESULTS: No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. CONCLUSIONS: Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Cães , Pirazóis/efeitos adversos , Sulfonamidas/efeitos adversos , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Feminino , Masculino , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia
12.
Am J Clin Dermatol ; 22(4): 541-554, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33954933

RESUMO

BACKGROUND: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life. OBJECTIVE: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy. METHODS: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients. RESULTS: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (- 11.4, - 8.2, and - 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (- 2.0, - 1.7, and - 1.0) and depression (- 1.7, - 1.3, and - 0.1). CONCLUSIONS: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes. CLINICAL TRIAL REGISTRATION: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018).


Assuntos
Dermatite Atópica/tratamento farmacológico , Inibidores de Janus Quinases/administração & dosagem , Prurido/tratamento farmacológico , Pirimidinas/administração & dosagem , Qualidade de Vida , Sulfonamidas/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Depressão/diagnóstico , Depressão/psicologia , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/psicologia , Eficiência , Fadiga/diagnóstico , Fadiga/psicologia , Feminino , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Prurido/complicações , Prurido/diagnóstico , Prurido/psicologia , Pirimidinas/efeitos adversos , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
13.
Urologiia ; (2): 40-45, 2021 May.
Artigo em Russo | MEDLINE | ID: mdl-33960155

RESUMO

INTRODUCTION: Daytime and nighttime urinary frequency is a common complaint in patients with benign prostatic hyperplasia (BPH). The most common reason for seeking elective surgery is an ineffective treatment with alpha-blockers. The aim of the study was to evaluate the efficacy and safety of combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg in patients with BPH and predominant irritative symptoms. MATERIALS AND METHODS: from January 2018 to December 2019 in the outpatient department of the city clinical hospital named after D.D. Pletnev, a total of 64 patients with BPH with complains of frequent nighttime and daytime frequency and a desire to undergo surgery were followed. The patients underwent a comprehensive clinical and laboratory examination, according to which 10 patients had indications for surgery, and they were excluded from the study. In 6 patients, the prevalence of nocturnal over daytime diuresis was revealed and they were also excluded. Combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg a day was prescribed to 48 patients. The average duration of therapy was 15.4 +/- 3.1 months. Patients underwent a follow-up examination to evaluate the efficiency and safety after 3, 6 and 12 months of therapy. Adverse events, possibly treatment-related, were recorded. RESULTS: there was an additional decrease in irritative complaints according to the I-PSS, namely 2 points after 3 months and 4 points after 6 and 12 months. In addition, a decrease in the number of nocturnal urinations by one, a decrease in daytime urination by one after 3 months and by two after 6 and 12 months, as well as an increase in the average voided volume from 150 +/- 33 to 240 +/- 40 ml after 12 months of therapy was seen. The change in other parameters was not significant. Two patients stopped taking the drug due to non-medical reasons. In other 2 patients, the development of sinus tachycardia and a transient increase in blood pressure were noted, which did not require discontinuation of the drug. CONCLUSIONS: Combination therapy with tamsulosin 0.4 mg and mirabegron 50 mg reduces the frequency of daytime and night urination with the maximum effect after 6-12 months, improves the quality of life and has a good safety profile.


Assuntos
Hiperplasia Prostática , Antagonistas Adrenérgicos alfa/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Tansulosina/uso terapêutico , Resultado do Tratamento
15.
Blood Adv ; 5(8): 2156-2164, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33885751

RESUMO

In patients with acute myeloid leukemia evolving from myeloproliferative neoplasms (post-MPN-AML), the clinical activity of the B-cell lymphoma 2 inhibitor venetoclax remains to be determined. We review our experience with venetoclax-based regimens in 14 newly diagnosed (frontline [FL]) and 17 relapsed/refractory (R/R) post-MPN-AML patients. Venetoclax was used in combination with hypomethylating agents in 58% of cases and in 19% with intensive chemotherapy (treatment including cytarabine ≥1 g/m2 or CPX-351); the remaining patients received cladribine and low-dose cytarabine or isocitrate dehydrogenase 1/2 inhibitors. The median dose of venetoclax during the initial cycle was 100 mg in all patients (range, 50-800 mg) and 200 mg (range, 100-800 mg) for FL patients. The venetoclax dose was adjusted when used concomitantly with azole antifungal agents. In FL patients, complete remission with and without count recovery in 6 patients (median duration of 6.4 months) and partial remission in 1 patient was noted, with a median overall survival of 7 months. In R/R patients, no formal responses were seen, with a median overall survival of 3 months. Hematologic toxicities and adverse events were frequent; 83% of patients developed grade 3 or higher infection during the initial cycle. Severe hemorrhagic complications were observed in 14 patients, including 6 cases of intracranial and subdural hemorrhage. Overall 4-week and 8-week mortality were 10% and 32%, respectively. Given the substantial treatment-associated hematologic toxicity and mortality, and modest short-lived responses only in newly diagnosed patients with venetoclax-based regimens, additional treatment options are urgently needed for these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/efeitos adversos
16.
Am J Clin Dermatol ; 22(3): 395-405, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33826132

RESUMO

BACKGROUND: Baricitinib, a selective Janus kinase 1/Janus kinase 2 inhibitor, is indicated in the European Union and Japan for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. OBJECTIVE: The objective of this study was to evaluate the safety of baricitinib 2 mg in the AD clinical program. METHODS: Six double-blind, randomized, placebo-controlled studies, and two long-term extension studies were summarized in two datasets. Placebo comparison was based on six 16-week studies with baricitinib 2 mg. All-bari-2-mg-AD included patients who received baricitinib 2 mg at any time during the eight studies. RESULTS: In total, 1598 patients received once-daily baricitinib 2 mg for 1434.2 patient-years of exposure (median 330 days/maximum 2.4 years). Treatment-emergent adverse events were higher for baricitinib 2 mg (57.9%) vs placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in frequency and similar between baricitinib 2 mg and placebo. There were no malignancies, gastrointestinal perforations, or major adverse cardiovascular events with baricitinib 2 mg in the placebo-controlled period. Herpes simplex (cluster) was higher for baricitinib 2 mg (3.8%) vs placebo (2.8%); rates decreased with extended 2 mg exposure. In All-bari-2-mg-AD, there were five malignancies other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths. CONCLUSIONS: This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. Longer exposure to treatment is required to evaluate risks of malignancies and major adverse cardiovascular events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02576938 (first posted 15 October, 2015); NCT03334396 (7 November, 2017); NCT03334422 (7 November, 2017); NCT03428100 (9 February, 2018); NCT03435081 (15 February, 2018); NCT03733301 (7 November, 2018); NCT03334435 (7 November, 2017); NCT03559270 (18 June, 2018).


Assuntos
Azetidinas/efeitos adversos , Dermatite Atópica/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Inibidores de Janus Quinases/efeitos adversos , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Sulfonamidas/efeitos adversos , Administração Oral , Adulto , Azetidinas/administração & dosagem , Dermatite Atópica/diagnóstico , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Seguimentos , Humanos , Inibidores de Janus Quinases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Adulto Jovem
17.
Crit Care ; 25(1): 160, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33910609

RESUMO

BACKGROUND: During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. METHODS: We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). RESULTS: Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). CONCLUSION: In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.


Assuntos
Arginina/análogos & derivados , Oxigenação por Membrana Extracorpórea/métodos , Heparina/normas , Ácidos Pipecólicos/normas , Sulfonamidas/normas , Trombocitopenia/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Antitrombinas/efeitos adversos , Antitrombinas/normas , Arginina/efeitos adversos , Arginina/normas , Estudos de Equivalência como Asunto , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Alemanha , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Pipecólicos/efeitos adversos , Pontuação de Propensão , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Sulfonamidas/efeitos adversos
18.
Ann Hematol ; 100(6): 1509-1516, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33900450

RESUMO

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.


Assuntos
Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Piperidinas/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/efeitos adversos , Resultado do Tratamento
19.
Bull Cancer ; 108(5): 528-543, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-33812673

RESUMO

Major therapeutic advances have been made recently in the treatment of metastatic melanoma, due to the development of targeted therapies, namely BRAF and MEK inhibitors, in patients with BRAF V600 mutation. Combinations of vemurafenib+cobimetinib, dabrafenib+trametinib, et encorafenib+binimetinib, evaluated in coBRIM, COMBI-d/COMBI-v and COLUMBUS trials respectively have been approved in this indication. Toxicities induced by combination therapies are different from those reported with monotherapies, in terms of frequency and intensity. Physicians who treat melanoma patients thus face news issues relating to prevention, detection and treatment of these adverse events. This paper summarizes tolerance data from the three pivotal trials (coBRIM, COMBI-v and COLUMBUS) and issues recommendations for the specific management of main toxicities, based on experts' opinion. We discuss dermatological, ophthalmological, cardiovascular, digestive, musculoskeletal, renal and general toxicities and propose a timetable for examinations to be performed before and during treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Carbamatos/efeitos adversos , Carbamatos/uso terapêutico , Combinação de Medicamentos , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Melanoma/patologia , Mutação , Oximas/efeitos adversos , Oximas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Pirimidinonas/efeitos adversos , Pirimidinonas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Vemurafenib/efeitos adversos , Vemurafenib/uso terapêutico
20.
Cochrane Database Syst Rev ; 3: CD004406, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33728634

RESUMO

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.


Assuntos
Antibacterianos/uso terapêutico , Faringite/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Humanos , Lactente , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Pessoa de Meia-Idade , Penicilinas/efeitos adversos , Penicilinas/uso terapêutico , Faringite/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Estreptocócicas/microbiologia , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Adulto Jovem
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