RESUMEN
Ruxolitinib cream 1.5% was first approved by the US Food and Drug Administration (FDA) in 2011. Opzelura™ cream was introduced by Incyte Dermatology in 2021 for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients aged ≥12 years, whose clinical manifestations are not controlled with prescribed topical therapies, such as topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase-4 ( PDE4) inhibitors, or when such therapies are not advisable. Ruxolitinib is a Janus kinase (JAK) inhibitor that addresses inflammation in AD. It selectively inhibits JAK1 and JAK2, blocking JAK and activating signal transducer and activator of transcription (STAT), thereby interrupting the cytokine pathways responsible for cutaneous inflammation. The targeted downstream cytokines include Interleukin- 4 (IL-4), IL-13, IL-31, and cytokine thymic stromal lymphopoietin (TSLP), which play pivotal roles in the itching and inflammation experienced by AD patients. Ruxolitinib cream is directly applied as a thin layer over AD lesions twice daily up to 20% body surface area (BSA) using no more than 60 g per week. It can be used for up to 8 weeks on delicate or thin skin surfaces.
Asunto(s)
Dermatitis Atópica , Nitrilos , Pirazoles , Pirimidinas , Humanos , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Nitrilos/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Crema para la Piel , Administración Cutánea , Citocinas/metabolismoRESUMEN
Chronic pulmonary aspergillosis (CPA) represents a spectrum of lung disorders caused by local proliferation of Aspergillus hyphae in individuals with non-systemic or mildly systemic immunodepression or altered pulmonary integrity due to underlying disease. While long-term systemic antifungal treatment is still the mainstay for management, surgery is considered mainly in rarer invasive disease manifestations such as sinusitis and osteomyelitis. Optimal application of existing antifungal agents with suitable pharmacokinetic properties is important for the treatment of diseases such as CPA, which requires long-term use. Appropriate management of side effects by therapeutic drug monitoring, maintenance of adherence, and assessment of drug resistance to Aspergillus can provide safe and effective treatment in the future. Most available antifungal agents for the management of mycoses in humans have disadvantages that can limit their use in clinical practice. By contrast, second generation antifungals such as triazoles have advantages of extended antifungal spectrum and availability in both oral and intravenous formulations. Isavuconazole, a new extended spectrum triazole, has been shown to be effective against Aspergillus. The safety profile and excellent pharmacokinetic characteristics of isavuconazole make it an attractive option for treatment of invasive fungal infections including CPA. With this drug now available in Japan, new evidence is expected to expand treatment options. This review focuses on the selection of antifungal agents based on national and international guidelines and the characteristics of each agent for their appropriate use in CPA.
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Antifúngicos , Aspergilosis Pulmonar , Triazoles , Humanos , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Aspergilosis Pulmonar/tratamiento farmacológico , Enfermedad Crónica , Triazoles/farmacocinética , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Aspergillus/efectos de los fármacos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/farmacocinética , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Nitrilos/farmacocinética , Farmacorresistencia FúngicaAsunto(s)
Antifúngicos , Nitrilos , Piridinas , Triazoles , Humanos , Triazoles/farmacocinética , Triazoles/administración & dosificación , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Piridinas/farmacocinética , Piridinas/administración & dosificación , Nitrilos/farmacocinética , Nitrilos/administración & dosificación , Infusiones Intravenosas , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Voluntarios SanosRESUMEN
BACKGROUND: Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged ≥ 75 is challenging due to limited data. Regardless of age, in real-world clinical practice, most mCRPC still derive from failure of androgen deprivation therapy (ADT) with or without docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC). As abiraterone acetate plus prednisone (AA) and enzalutamide (Enza) are common first-line treatments for mCRPC. The impact of prior use of D for mCSPC on the efficacy and safety of AA or Enza in this older population remains unclear. METHODS: A cohort of patients aged ≥ 75 years starting AA or Enza as first-line therapy for mCRPC from January 2015 to April 2019 was identified from the registries of 10 institutions. Patients were categorized into 2 groups based on previous use of D for mCSPC. Primary endpoints were cancer-specific survival (CSS) from AA or Enza start, CSS from ADT onset, and safety. We used Kaplan-Meier method to estimate the endpoints distribution, including median values with 95% confidence intervals (95% CI). RESULTS: Of the 337 patients identified, 24 (7.1%) received ADT+D and 313 (92.9%) received ADT alone for mCSPC. Median follow-up from AA/Enza start was 18.8 months. Median CSS from ADT or AA/Enza was not significantly different between ADT+D and ADT alone cohorts (71.9 vs. 52.7 months, P = .97; 25.4 vs. 27.2 months, P = .89, respectively). No statistically significant difference in adverse events (AEs) of any grade rate (58.3% vs. 52.1%, respectively; P = .67) or grade ≥ 3 (12.5% vs. 15.7%, respectively; P = 1.0) was found between ADT+D and ADT alone cohorts. CONCLUSIONS: Despite the innate limitations of a retrospective design and relatively small size of the ADT+D cohort, this analysis suggests that elderly men receiving AA or Enza as first-line therapy for mCRPC have similar survival outcomes and tolerability, regardless of previous D for mCSPC.
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Acetato de Abiraterona , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Sistema de Registros , Humanos , Masculino , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Anciano , Acetato de Abiraterona/uso terapéutico , Acetato de Abiraterona/administración & dosificación , Nitrilos/administración & dosificación , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Anciano de 80 o más Años , Sistema de Registros/estadística & datos numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Prednisona/administración & dosificación , Prednisona/uso terapéuticoRESUMEN
The effectiveness of a visceral leishmaniasis (VL) control strategy based on the application of 4 % deltamethrin impregnated collars (DIC) exclusively in seropositive dogs was assessed between 2018 and 2019, through a prospective study. The effectiveness of DIC-collaring was evaluated by comparing the incidence rate of anti-leishmanial antibodies among dogs from two endemic districts in Brazil. In one of the areas, the conventional control measure which is based on the non-compulsory euthanasia of LV seropositive dogs, was practiced by the official healthy service as a regular procedure, whereas strategic collaring, conceived in this study, was carried out in the other. Results of serological tests applied to serum samples collected from all domiciled dogs were evaluated in three consecutive times, spaced by around 200 days. Incidence rates of VL seroreactivity were compared between districts in the same period of time as well as within the same district, in consecutive periods. Based on the results, the risk of infection in the population under conventional control measure was up to four times higher than the risk of infection where DIC-collaring was used. The strategic use of collar proposed here emerged as a promising measure for VL control in dogs from endemic areas. Strategic collaring does not rely on the euthanasia of infected animals, an extremely controversial procedure, and instead of being used in all dogs, as collaring is normally recommended; only seropositive dogs are intervened. Strategic use of DIC has the potential to drastically reduce costs, if compared to mass collaring canine population.
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Enfermedades de los Perros , Insecticidas , Leishmaniasis Visceral , Nitrilos , Piretrinas , Animales , Perros , Leishmaniasis Visceral/veterinaria , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/epidemiología , Piretrinas/administración & dosificación , Piretrinas/farmacología , Enfermedades de los Perros/prevención & control , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Nitrilos/administración & dosificación , Nitrilos/farmacología , Brasil/epidemiología , Insecticidas/administración & dosificación , Incidencia , Estudios Prospectivos , Anticuerpos Antiprotozoarios/sangre , Masculino , FemeninoRESUMEN
Lipid-based formulations (LbFs) have demonstrated success in pharmaceutical applications; however, challenges persist in dissolving entire doses of the drug into defined liquid volumes. In this study, the temperature-induced supersaturation method was employed in LbF to address drug loading and pill burden issues. Supersaturated LbFs (super-LbF) were prepared using the temperature-induced supersaturation method, where the drug load is above its equilibrium solubility. Further, the influence of the drug's physicochemical and thermal characteristics on drug loading and their relevance with an apparent degree of supersaturation (aDS) was studied using two model drugs, ibrutinib and enzalutamide. All the prepared LbFs were evaluated in terms of physical stability, dispersion, and solubilization capacity, as well as pharmacokinetic assessments. Drug re-crystallization was observed in the lipid solution on long-term storage at higher aDS values of 2-2.5. Furthermore, high-throughput lipolysis studies demonstrated a significant decrease in drug concentration across all LbFs (regardless of drug loading) due to a decline in the formulation solvation capacity and subsequent generation of in-situ supersaturation. Further, the in vivo results demonstrated comparable pharmacokinetic parameters between conventional LbF and super-LbF. The short duration of the thermodynamic metastable state limits the potential absorption benefits. However, super-LbFs of Ibr and Enz showed superior profiles, with 1.7-fold and 5.2-fold increased drug exposure compared to their respective crystalline suspensions. In summary, this study emphasizes the potential of temperature-induced supersaturation in LbF for enhancing drug loading and highlights the intricate interplay between drug properties, formulation characteristics, and in vivo performance.
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Adenina , Benzamidas , Química Farmacéutica , Lípidos , Nitrilos , Feniltiohidantoína , Piperidinas , Solubilidad , Temperatura , Nitrilos/química , Nitrilos/administración & dosificación , Piperidinas/química , Piperidinas/administración & dosificación , Piperidinas/farmacocinética , Benzamidas/química , Benzamidas/farmacocinética , Adenina/análogos & derivados , Adenina/química , Adenina/administración & dosificación , Feniltiohidantoína/farmacocinética , Feniltiohidantoína/administración & dosificación , Lípidos/química , Animales , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Masculino , Pirimidinas/farmacocinética , Pirimidinas/química , Pirimidinas/administración & dosificación , Estabilidad de Medicamentos , Cristalización/métodos , Pirazoles/química , Pirazoles/farmacocinética , Pirazoles/administración & dosificación , Lipólisis/efectos de los fármacos , RatasRESUMEN
OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.
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Antifúngicos , Nitrilos , Piridinas , Triazoles , Humanos , Triazoles/farmacocinética , Triazoles/administración & dosificación , Antifúngicos/farmacocinética , Antifúngicos/administración & dosificación , Nitrilos/farmacocinética , Nitrilos/administración & dosificación , Piridinas/farmacocinética , Piridinas/administración & dosificación , Administración Oral , Niño , Preescolar , Lactante , Adulto , Adolescente , Adulto Joven , Masculino , Persona de Mediana Edad , Femenino , Anciano , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Modelos BiológicosRESUMEN
AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.
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Antagonistas de Receptores Androgénicos , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Receptores Androgénicos/administración & dosificación , Antagonistas de Receptores Androgénicos/efectos adversos , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Flutamida/administración & dosificación , Flutamida/efectos adversos , Metaanálisis en Red , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Feniltiohidantoína/administración & dosificación , Feniltiohidantoína/efectos adversos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Tiohidantoínas/administración & dosificación , Tiohidantoínas/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Therapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible. METHODS: We evaluated drug cohorts from the Dutch Pharmacology Oncology Group - TDM study. Based on PK levels taken at pre-specified time points, PK-guided interventions were performed. Feasibility of TDM was evaluated, and based on the success and practicability of TDM, cohorts could be closed. RESULTS: For 10 out of 24 cohorts TDM was not feasible and inclusion was closed. A high incidence of adverse events resulted in closing the cabozantinib, dabrafenib/trametinib, everolimus, regorafenib and vismodegib cohort. The enzalutamide and erlotinib cohorts were closed because almost all PK levels were above target. Other, non-pharmacological reasons led to closing the palbociclib, olaparib and tamoxifen cohort. CONCLUSIONS: Although TDM could help personalising treatment for many drugs, the above-mentioned reasons can influence its feasibility, usefulness and clinical applicability. Therefore, routine TDM is not advised for cabozantinib, dabrafenib/trametinib, enzalutamide, erlotinib, everolimus, regorafenib and vismodegib. Nonetheless, TDM remains valuable for individual clinical decisions.
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Monitoreo de Drogas , Neoplasias , Piridinas , Humanos , Monitoreo de Drogas/métodos , Estudios Prospectivos , Neoplasias/tratamiento farmacológico , Piridinas/farmacocinética , Piridinas/administración & dosificación , Estudios de Factibilidad , Administración Oral , Antineoplásicos/farmacocinética , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Terapia Molecular Dirigida , Imidazoles/farmacocinética , Imidazoles/administración & dosificación , Anilidas/farmacocinética , Anilidas/administración & dosificación , Masculino , Everolimus/farmacocinética , Everolimus/administración & dosificación , Femenino , Oximas/farmacocinética , Oximas/administración & dosificación , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/farmacocinética , Feniltiohidantoína/administración & dosificación , Nitrilos/farmacocinética , Nitrilos/administración & dosificación , Compuestos de Fenilurea , Piridonas , Pirimidinonas , Piperazinas , BenzamidasRESUMEN
Deltamethrin (DLM) is a newer kind of insecticide that is used on pets, livestock, and crops, as well as to combat malaria vectors and household pests. It belongs to the synthetic pyrethroid group and is being promoted as an alternative to organophosphate chemicals due to its persistent and destructive effects. The current study aimed to evaluate the impact of sub-chronic oral exposure to DLM on autoimmune activity in rats. Three groups of male albino rats (15 rats/group) including the control group, the ethanol-treated group (1 ml/rat), and the DLM-treated group (5 mg/kg b.w). Samples of blood were taken from all groups at 4-, 8- and 12-week intervals for the determination of hematological, cytokines, and immunological parameters. T lymphocyte subsets and Treg lymphocytes were determined in serum using flow cytometric acquisition. The results revealed that DLM significantly increased TNF-α, IL-33, IL-6, IL-17, IgG, IgM, WBCs, differential count, and platelets while decreasing Hb concentration and RBCs. Additionally, DLM decreased the number of T-cell subsets (CD3, CD4, CD5, and CD8) and Treg lymphocytes. All of these impacts became more severe over time. It is possible to conclude that the sub-chronic oral exposure to DLM disturbed autoimmune activity through the disturbances in immunological indices, CDs subset Treg lymphocytes.
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Insecticidas , Nitrilos , Piretrinas , Animales , Piretrinas/toxicidad , Piretrinas/administración & dosificación , Nitrilos/toxicidad , Nitrilos/farmacología , Nitrilos/administración & dosificación , Masculino , Ratas , Insecticidas/toxicidad , Citocinas/sangre , Citocinas/metabolismo , Autoinmunidad/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/sangre , Ratas WistarRESUMEN
BACKGROUND/AIM: Vildagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have been shown to improve hyperglycemia in clinical trials among patients with type 2 diabetes. However, few studies have examined the efficacy of vildagliptin in patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: Eight patients with DKD received oral vildagliptin 50-100 mg/day. The duration of diabetes was 6.7±5.9 years and observation period was 23.6±9.8 months. Changes in fasting blood glucose, and hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR) were studied before and after the administration of vildagliptin. RESULTS: Vildagliptin treatment significantly decreased fasting blood glucose and HbA1c, compared to baseline (132±56 mg/dl, p=0.036, 6.0±0.3, p=0.041, respectively). UPCR tended to be decreased, albeit without statistical significance. However, eGFR was decreased after the administration of vildagliptin. No significant adverse effects were observed in all patients during the study. CONCLUSION: Although the sample size was limited and the observation period was brief, vildagliptin was found to be an effective and reasonably well-tolerated treatment for patients with DKD.
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Adamantano , Glucemia , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inhibidores de la Dipeptidil-Peptidasa IV , Tasa de Filtración Glomerular , Hemoglobina Glucada , Nitrilos , Pirrolidinas , Vildagliptina , Humanos , Vildagliptina/uso terapéutico , Vildagliptina/efectos adversos , Vildagliptina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Nefropatías Diabéticas/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Tasa de Filtración Glomerular/efectos de los fármacos , Glucemia/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Adamantano/efectos adversos , Resultado del Tratamiento , Pirrolidinas/uso terapéutico , Pirrolidinas/efectos adversos , Pirrolidinas/administración & dosificación , Nitrilos/uso terapéutico , Nitrilos/efectos adversos , Nitrilos/administración & dosificación , Creatinina/sangreRESUMEN
BACKGROUND: Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure. METHODS: Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7â days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60â mg·h/L. RESULTS: Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7â days was above 60â mg·h/L in 29 out of 77 (37.7%) patients. CONCLUSIONS: This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.
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Antifúngicos , Infecciones Fúngicas Invasoras , Nitrilos , Piridinas , Triazoles , Humanos , Piridinas/uso terapéutico , Piridinas/efectos adversos , Piridinas/administración & dosificación , Triazoles/uso terapéutico , Triazoles/efectos adversos , Triazoles/administración & dosificación , Nitrilos/uso terapéutico , Nitrilos/efectos adversos , Nitrilos/administración & dosificación , Antifúngicos/uso terapéutico , Antifúngicos/efectos adversos , Antifúngicos/administración & dosificación , Estudios Retrospectivos , Femenino , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/prevención & control , Masculino , Persona de Mediana Edad , Anciano , Adulto , Monitoreo de Drogas , Anciano de 80 o más Años , Adulto JovenRESUMEN
BACKGROUND: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles. OBJECTIVE: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL]. METHODS: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment. RESULTS: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139). CONCLUSIONS: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL.
Asunto(s)
Alopecia , Anilidas , Nitrilos , Espironolactona , Compuestos de Tosilo , Humanos , Femenino , Espironolactona/uso terapéutico , Espironolactona/efectos adversos , Anilidas/efectos adversos , Anilidas/uso terapéutico , Estudios Retrospectivos , Alopecia/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Compuestos de Tosilo/efectos adversos , Compuestos de Tosilo/uso terapéutico , Nitrilos/efectos adversos , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Adulto Joven , Minoxidil/uso terapéutico , Minoxidil/efectos adversos , Resultado del Tratamiento , Adolescente , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Asunto(s)
Antagonistas de Andrógenos , Anilidas , Nitrilos , Prostatectomía , Neoplasias de la Próstata , Compuestos de Tosilo , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Andrógenos/administración & dosificación , Anciano , Compuestos de Tosilo/uso terapéutico , Compuestos de Tosilo/administración & dosificación , Anilidas/uso terapéutico , Anilidas/administración & dosificación , Persona de Mediana Edad , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Oligopéptidos/uso terapéutico , Oligopéptidos/administración & dosificación , Hormona Liberadora de Gonadotropina/agonistas , Terapia Combinada , Antígeno Prostático Específico/sangreRESUMEN
BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Asunto(s)
Antagonistas de Andrógenos , Anilidas , Nitrilos , Prostatectomía , Neoplasias de la Próstata , Compuestos de Tosilo , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/cirugía , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Andrógenos/administración & dosificación , Anciano , Compuestos de Tosilo/uso terapéutico , Compuestos de Tosilo/administración & dosificación , Persona de Mediana Edad , Anilidas/uso terapéutico , Anilidas/administración & dosificación , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Oligopéptidos/administración & dosificación , Oligopéptidos/uso terapéutico , Hormona Liberadora de Gonadotropina/agonistas , Antígeno Prostático Específico/sangre , Terapia Combinada , Esquema de MedicaciónRESUMEN
Alopecia areata (AA) is a common autoimmune disorder. Although its pathogenesis is not fully understood, AA involves CD8 T cell-mediated destruction of the hair follicle. Several treatment options exist; however, there is minimal evidence in the pediatric population. Currently, there are no curative treatments for AA. The literature suggests that Janus kinase (JAK) inhibitors may be an effective treat-ment for AA, but evidence in pediatric patients is limited. Here, we report a case of severe pediatric AA treated with topical ruxolitinib, a JAK inhibitor. J Drugs Dermatol. 2024;23(5):378-379. doi:10.36849/JDD.7782.
Asunto(s)
Alopecia Areata , Inhibidores de las Cinasas Janus , Nitrilos , Pirazoles , Pirimidinas , Niño , Humanos , Administración Cutánea , Alopecia Areata/tratamiento farmacológico , Inhibidores de las Cinasas Janus/administración & dosificación , Inhibidores de las Cinasas Janus/uso terapéutico , Nitrilos/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Crema para la Piel/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.
Asunto(s)
Antagonistas de Andrógenos , Antagonistas de Receptores Androgénicos , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Acetato de Abiraterona/uso terapéutico , Acetato de Abiraterona/administración & dosificación , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Receptores Androgénicos/administración & dosificación , Antagonistas de Receptores Androgénicos/uso terapéutico , Anilidas/uso terapéutico , Anilidas/administración & dosificación , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Pueblos del Este de Asia , Japón/epidemiología , Metástasis de la Neoplasia , Nitrilos/administración & dosificación , Nitrilos/uso terapéutico , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Pronóstico , Supervivencia sin Progresión , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/sangre , Estudios Retrospectivos , Tiohidantoínas/uso terapéutico , Tiohidantoínas/administración & dosificación , Compuestos de Tosilo/uso terapéutico , Compuestos de Tosilo/administración & dosificaciónRESUMEN
PURPOSE: We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-α-positive breast cancer planning to receive adjuvant ANA1 were eligible. E1 and E2 were assessed pre- and post-8 to 10 weeks of ANA1. Those with IES were switched to 8- to 10-week cycles of ANA10 followed by letrozole 2.5 mg/day. E1 and E2 were assessed after each cycle. Anastrozole concentrations were measured post-ANA1 and post-ANA10. Primary analyses included patients who documented taking at least 80% of the planned treatment (adherent cohort). RESULTS: In total, 132 (84.6%) of 156 eligible patients were ANA1 adherent. IES occurred in 40 (30.3%) adherent patients. Twenty-five (78.1%) of 32 patients who began ANA10 were adherent, and AES was achieved in 19 (76.0%; 90% confidence interval, 58.1%-89.0%) patients. Anastrozole concentrations post-ANA1 and post-ANA10 did not differ by estrogen suppression status among adherent patients. AES was maintained/attained in 21 (91.3%) of 23 letrozole-adherent patients. CONCLUSIONS: Approximately 30% of ANA1-adherent patients had IES. Among those who switched to ANA10 and were adherent, 76% had AES. Further studies are required to validate emerging data that ANA1 results in IES for some patients and to determine the clinical benefit of switching to ANA10 or an alternative aromatase inhibitor.
Asunto(s)
Anastrozol , Neoplasias de la Mama , Nitrilos , Posmenopausia , Triazoles , Humanos , Anastrozol/administración & dosificación , Anastrozol/uso terapéutico , Anastrozol/efectos adversos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Persona de Mediana Edad , Anciano , Triazoles/administración & dosificación , Triazoles/efectos adversos , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Estrógenos/administración & dosificación , Estadificación de Neoplasias , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Estudios Prospectivos , Estradiol/administración & dosificación , Estrona/sangre , Estrona/administración & dosificación , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/efectos adversosRESUMEN
Vitiligo is a chronic skin condition caused by an autoimmune response that results in the progressive loss of melanocytes and recent studies have suggested that Janus kinase inhibitors (JAKi) are emerging as a promising new treatment modality. Therefore, to assess and understand the extent of knowledge in the emerging field of JAKi use in vitiligo, a scoping review of the literature was undertaken. The reviewed articles explored a wide variety of JAKi administered either orally or topically for vitiligo. There were no injectable JAKi studied. Tofacitinib was the most commonly studied oral JAKi in 16 of the 35 studies selected for review, followed by baricitinib (n = 3), and one study each with ritlecitinib, ruxolitinib, and upadacitinib. Ruxolitinib (n = 6) and tofacitinib (n = 6) were the most often studied topical JAKi, followed by delgocitinib (n = 1). Potential benefits may vary between JAKi based on their receptor selectivity profile and coexistent autoimmune diseases. A topical JAKi would be advantageous in limited body area involvement and in adolescents. Concurrent use of JAKi with phototherapy or sun exposure appears beneficial. Most studies permitted the use of other topical agents. Acne-related events, though frequent yet mild, were reported with both oral and topical JAKi. Nasopharyngitis, upper respiratory tract infections, and headaches were the most common adverse effects seen in the larger trials with JAKi. No serious or clinically meaningful hematology or thromboembolic events were detected. Treatment of vitiligo with oral or topical JAKi seems to be promising and the growing evidence shows a favorable risk-benefit profile.