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PURPOSE: This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards. METHODS: The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). CONCLUSIONS: The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer.
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Anticuerpos Monoclonales Humanizados , Neoplasias del Cuello Uterino , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Bevacizumab/uso terapéutico , Bevacizumab/efectos adversos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patologíaRESUMEN
WHAT IS THIS SUMMARY ABOUT?: Generalized myasthenia gravis (often shortened to gMG) is a rare health condition that causes muscular weakness. This summary gives an overview of three published articles that report the results of research studies of a medicine called ravulizumab, a treatment approved for adults with gMG. These studies are: The CHAMPION MG study. The CHAMPION MG extension study. A study of how the body processes and responds to ravulizumab (known as pharmacokinetics and pharmacodynamics). These studies looked at how effective and safe ravulizumab is for people with gMG. WHAT WERE THE RESULTS?: Overall, participants with gMG who received ravulizumab showed a significant and rapid improvement in their muscle strength and ability to do daily activities. These improvements were sustained for up to 60 weeks of treatment. Ravulizumab was well-tolerated overall, and no-one in the study had a meningococcal infection (a type of bacterial infection preventable with vaccination). Results from the pharmacokinetic and pharmacodynamic study support the use of ravulizumab every 8 weeks to maintain improvements in gMG. WHAT DO THE RESULTS OF THE STUDY MEAN?: Ravulizumab can be considered as a treatment option for adults with gMG who are appropriately protected against meningococcal infection before starting treatment. The drug, administered every 8 weeks, improves muscle strength and daily performance. These positive effects have been observed to persist over a long period of time.
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Anticuerpos Monoclonales Humanizados , Miastenia Gravis , Humanos , Miastenia Gravis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Fuerza Muscular/efectos de los fármacos , Inhibidores de la Colinesterasa/uso terapéutico , Femenino , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Mieloma Múltiple , Mieloma Múltiple/tratamiento farmacológico , Humanos , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Bortezomib/efectos adversos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Compuestos de Boro/uso terapéutico , Compuestos de Boro/administración & dosificación , Compuestos de Boro/efectos adversosAsunto(s)
Inhibidores de la Angiogénesis , Bevacizumab , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Humanos , Bevacizumab/uso terapéutico , Edema Macular/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Brasil , Resultado del Tratamiento , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Persona de Mediana EdadRESUMEN
Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Células Asesinas Naturales , Terapia Neoadyuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Femenino , Terapia Neoadyuvante/métodos , Receptor ErbB-2/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , AncianoRESUMEN
BACKGROUND AND AIMS: Vedolizumab is a humanized gut selective drug that targets α4ß7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. METHODS: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. CONCLUSIONS: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.
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Anticuerpos Monoclonales Humanizados , Artralgia , Artritis , Fármacos Gastrointestinales , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Artralgia/inducido químicamente , Artralgia/epidemiología , Artralgia/diagnóstico , Artritis/inducido químicamente , Artritis/diagnóstico , Artritis/epidemiología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del TratamientoRESUMEN
Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.
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Citocinas , Modelos Animales de Enfermedad , Ratas Wistar , Receptores de Interleucina-6 , Cráneo , Animales , Masculino , Citocinas/metabolismo , Receptores de Interleucina-6/antagonistas & inhibidores , Cráneo/efectos de los fármacos , Ratas , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Microtomografía por Rayos X , Péptido Hidrolasas/metabolismo , Inmunohistoquímica , Distribución AleatoriaRESUMEN
INTRODUÇÃO: Os CECP desenvolvem-se a partir do epitélio da mucosa na cavidade oral, faringe e laringe e são as neoplasias malignas mais comuns que surgem na cabeça e pescoço. Aproximadamente 40% dos cânceres de cabeça e pescoço ocorrem na região de cavidade oral; 15% na faringe; 25% na laringe; e o restante em glândulas salivares e tireoide. Estudos clínicos em pacientes com CECP recidivado ou metastático indicam que os medicamentos mais ativos são o metotrexato, cisplatina, fluorouracila, bleomicina, paclitaxel e docetaxel. No entanto, esses medicamentos produziram taxas de resposta da ordem de 20%-30%, com curta duração (3-5 meses) e raramente respostas completas. Devido às evidências do regime EXTREME (cetuximabe, cisplatina e 5-fluorouracil) demonstrarem um aumento significativo no tempo de sobrevida global em comparação com o grupo controle com menos eventos adversos, o regime foi estabelecido como o tratamento padrão de primeira linha. Adicionalmente, devido ao pembrolizumabe ativar a resposta do sistema imunológico contra o câncer, a imunoterapia também tem sido uma opção de primeira linha para tratamento de pacientes com CECP recidivado ou metastático, especialmente em expressores de PD-1, aproximadamente 85% dos cas
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Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Cetuximab/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Sistema Único de Salud , Brasil , Eficacia , Análisis Costo-Beneficio/economíaRESUMEN
Background: HER-2 positive (+) breast cancer (BC) accounts for 20-25% of BC, it is more aggressive, and it has a lower survival rate. Since the approval of trastuzumab in 1998, other HER-2-targeted therapies such as pertuzumab and trastuzumab emtansine (TDM1) have been introduced, improving patient survival. However, cardiotoxicity is an adverse effect of these treatments. Objective: To estimate the incidence of cardiotoxicity with trastuzumab, trastuzumab/pertuzumab, and TDM1 in women with HER-2 + BC treated over a 6-year period at the Hospital de Clínicas and the Hospital Departamental de Soriano. Material and methods: Observational, descriptive, and retrospective study which included patients with HER-2 + BC treated with trastuzumab, trastuzumab/pertuzumab, or TDM1. Results: 81 patients were included, with a cardiotoxicity incidence of 23.4%. Cardiotoxicity was determined by a > 10% decrease in left ventricular ejection fraction (LVEF) (57.9%) and a LVEF < 50% evident during treatment (42.1%). Only 1 patient presented symptomatic heart failure. 63.1% of those who discontinued treatment due to cardiotoxicity managed to resume it. No relationship was evident between cardiovascular history or the administration regimen and the development of cardiotoxicity. Conclusion: The study showed a cardiotoxicity incidence similar to the international one. Most did not present cardiac toxicity, and if they did, it was asymptomatic and reversible.
Introducción: el cáncer de mama (CM) HER-2 positivo (+) representa el 20-25% de los CM, es más agresivo y tiene menor sobrevida. Desde la aprobación del trastuzumab en 1998, se han introducido otras terapias dirigidas al HER-2 como pertuzumab y trastuzumab emtansina (TDM1), con lo cual ha mejorado la supervivencia de las pacientes. Sin embargo, la cardiotoxicidad representa un efecto adverso de estos tratamientos. Objetivo: estimar la incidencia de cardiotoxicidad con trastuzumab, trastuzumab/pertuzumab y TDM1 en mujeres con CM HER-2 +, tratadas en un periodo de 6 años en el Hospital de Clínicas y el Hospital Departamental de Soriano. Material y métodos: estudio observacional, descriptivo y retrospectivo que incluyó pacientes con CM HER-2 +, tratadas con trastuzumab, trastuzumab/pertuzumab o TDM1. Resultados: se incluyeron 81 pacientes. La incidencia de cardiotoxicidad fue del 23.4%. La cardiotoxicidad se determinó por una disminución > 10% de la fracción de ejección del venticulo izquierdo (FEVI) (57.9%) y por una FEVI < 50%, evidenciada durante el tratamiento (42.1%). Únicamente una paciente presentó insuficiencia cardiaca sintomática. El 63.1% de quienes suspendieron el tratamiento por cardiotoxicidad logró reanudarlo. No se evidenció una relación entre los antecedentes cardiovasculares ni con el esquema de administración y el desarrollo de cardiotoxicidad. Conclusión: el estudio mostró una incidencia de cardiotoxicidad similar a la internacional. La mayoría no tuvo toxicidad cardiaca y si la hubo fue asintomática y reversible.
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Ado-Trastuzumab Emtansina , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama , Cardiotoxicidad , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Cardiotoxicidad/etiología , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Trastuzumab/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anciano , Adulto , Ado-Trastuzumab Emtansina/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Incidencia , Maitansina/análogos & derivados , Maitansina/efectos adversosRESUMEN
Atopic dermatitis (AD) is a chronic, non-infectious inflammatory dermatosis, with increasing prevalence in recent decades. Due to its chronic and recurrent nature, it diminishes the quality of life of patients and their families. In recent years, advances in the understanding of AD's pathophysiology have driven the development of targeted therapies such as monoclonal antibodies (mAbs) and Janus kinase inhibitors (JAKis) which modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. Four targeted therapies have been approved in the USA for the treatment of severe/refractory cases: dupilumab, tralokinumab, abrocitinib, and upadacitinib. This manuscript aims to present an update on the pathophysiology of AD, describe the new treatments available, and provide an analysis of the initial results of the use of these treatments in the pediatric population. We concluded that the high cost of these treatments often limits their prescription to situations where cases of atopic dermatitis are resistant to other conventional therapeutic options or when the disease reaches a severe degree. This underscores the importance of careful and accurate decision-making in the medical management of AD to ensure the efficient use of these therapeutic resources.
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Dermatitis Atópica , Medicina de Precisión , Dermatitis Atópica/tratamiento farmacológico , Humanos , Niño , Inhibidores de las Cinasas Janus/uso terapéutico , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Terapia Molecular Dirigida/métodos , Pirimidinas , SulfonamidasRESUMEN
BACKGROUND: The efficacy and safety of secukinumab in psoriasis patients has been demonstrated in randomized controlled clinical trials. OBJECTIVES: The authors aimed to evaluate the efficacy and safety of secukinumab in plaque psoriasis patients followed in our clinic. METHODS: Data from 101 plaque psoriasis patients who received at least 16 weeks of secukinumab treatment between June 2018 and June 2023 were retrospectively analyzed. RESULTS: Fifty-three (53%) of the patients were bionaive. PASI-75, -90, -100 response rates were 72%, 50%, 30% respectively at week 16 in all patients. PASI-75 and -90 responses were higher in naive patients at weeks 16 and 28 (pâ¯<â¯0.001, pâ¯<â¯0.001, pâ¯<â¯0.01, pâ¯=â¯0.01, respectively). The percentage of patients with PASIâ¯≤â¯1, ≤ 3, ≤ 5 were 50%, 77%, and 92%, respectively at week 16. They were higher in the naive group than in nonnaive group at weeks 16 and 28 (pâ¯=â¯0.02, pâ¯<â¯0.01, pâ¯=â¯0.05, pâ¯=â¯0.07, pâ¯<â¯0.01, pâ¯=â¯0.03, respectively). At week 52, PASI-75, -90, -100 responses were significantly lower in smoking patients (pâ¯=â¯0.04, pâ¯=â¯0.03, pâ¯<â¯0.01, respectively). The mean duration of secukinumab treatment was 19.80⯱â¯12.76 months. Secukinumab was discontinued 14 (26.4%) naive patients and 28 (58.3%) nonnaive patients at one occasion during treatment (pâ¯<â¯0.001). The most common adverse event in patients was mucocutaneous candida infection (8%). No hepatitis B or C reactivation and no active or reactivation tuberculosis were observed in any of the patients during the follow-up period. STUDY LIMITATIONS: This is a single-center retrospective study with relatively few patients including only the Turkish population. CONCLUSION: Secukinumab seems to be effective in plaque psoriasis, particularly in bionaive and non-smokers. Moreover, it is safe in patients with inactive hepatitis or tuberculosis.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Índice de Severidad de la Enfermedad , Anciano , Factores de TiempoRESUMEN
Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, type-2 inflammatory disease with the potential to significantly impact an individual's quality of life. Conventional treatments often result in varied responses, prompting the need for novel therapeutic approaches. We present the case of a 19-year-old male with a medical history marked by eosinophilic esophagitis, severe atopic dermatitis (AD), asthma, and allergic rhinitis. Despite undergoing diverse topical and systemic interventions to address his AD and EoE, the patient's symptoms persisted. However, following the initiation of dupilumab therapy-a dual IL-4 and IL-13 receptor antagonist-the patient experienced a substantial reduction in his Eczema Area and Severity Index score. Notably, a marked improvement was also seen regarding his symptoms of eosinophilic esophagitis. A subsequent esophageal biopsy revealed a significant decrease in eosinophilic inflammation, consistent with established clinical and histologic remission criteria. These findings corroborate the patient's reported relief from symptoms. This case underscores the potential efficacy of dupilumab as a promising therapeutic agent in managing eosinophilic esophagitis. Dupilumab offers a dual benefit of alleviating symptoms and achieving histologic and clinical remission. This novel approach presents a noteworthy advancement in the treatment of EoE.
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Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Esofagitis Eosinofílica , Humanos , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Adulto Joven , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/patología , Asma/tratamiento farmacológico , Asma/complicaciones , Inducción de RemisiónRESUMEN
BACKGROUND: Evidence describing the types and annual costs of biological treatments for psoriasis in Latin America is scarce. This study aimed to estimate the frequency of use and costs of biologic therapy for psoriasis in Colombia in 2019. METHODS: This secondary data analysis uses the International Classification of Diseases terms associated with psoriasis, excluding those related to psoriatic arthritis, based on data from the registry of the Colombian Ministry of Health. We estimated the prevalence of psoriasis per 100,000 inhabitants; then, we retrieved the frequency of use of biologic therapy in patients with psoriasis and estimated the cost per year of each and overall therapies in 2019 in US dollars (USD). RESULTS: There were 100,823 patients with psoriasis in Colombia in 2019, which amounts to a prevalence of 0.2% in the general population. Of those patients, 4.9% received biologic therapy, most frequently males (60%). The most commonly used biological therapies for psoriasis in Colombia in 2019 were ustekinumab (35.2%), with an annual cost per patient of $12,880 USD; adalimumab (26%), with a yearly cost per patient of $7130 USD; and secukinumab (19.8%), with an annual cost per patient of $6825 USD. CONCLUSION: This is the first study to describe the use and cost of biological therapy for psoriasis in Colombia. It provides valuable cost-awareness information for the Colombian health system.
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Adalimumab , Terapia Biológica , Psoriasis , Humanos , Psoriasis/economía , Psoriasis/tratamiento farmacológico , Psoriasis/terapia , Psoriasis/epidemiología , Colombia/epidemiología , Masculino , Femenino , Adalimumab/uso terapéutico , Adalimumab/economía , Adulto , Persona de Mediana Edad , Terapia Biológica/economía , Terapia Biológica/estadística & datos numéricos , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ustekinumab/uso terapéutico , Ustekinumab/economía , Prevalencia , Adulto Joven , Fármacos Dermatológicos/economía , Fármacos Dermatológicos/uso terapéutico , Anciano , Sistema de Registros/estadística & datos numéricos , Costos de los Medicamentos/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , AdolescenteRESUMEN
Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development. Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment. Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023. Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded. Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted. Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model. Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.
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Leucemia Linfocítica Crónica de Células B , Neoplasia Residual , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Supervivencia sin Progresión , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients. METHODS AND ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively. RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk. CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients. PROSPERO REGISTRATION NUMBER: CRD42023394226.
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Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Metaanálisis en Red , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Agudeza Visual/efectos de los fármacos , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificaciónRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.
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Enfermedad de Raynaud , Reumatología , Esclerodermia Sistémica , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Humanos , Brasil , Reumatología/normas , Enfermedad de Raynaud/tratamiento farmacológico , Sociedades Médicas , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Rituximab/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Cutánea/etiología , Antirreumáticos/uso terapéuticoRESUMEN
BACKGROUND: Thyroid eye disease (TED), a common extrathyroidal manifestation of Graves disease, poses significant management challenges due to potential disfigurement, visual impairment, and decreased quality of life. Uncertainties remain about the optimal treatment approach, especially regarding TED duration and its impact on outcomes. OBJECTIVE: This meta-analysis evaluates the effects of various treatments on inflammatory markers and severity endpoints in TED, stratified by disease duration, distinguishing between treatments initiated within the first 6 months (initial phase) and those initiated thereafter (subacute/chronic phase). METHODS: Following PRISMA guidelines, a systematic search of multiple electronic databases yielded 26 studies meeting predefined inclusion criteria. Methodological quality was assessed, and data were meticulously extracted and analyzed. RESULTS: In the initial phase, treatments like corticosteroids and teprotumumab showed significant improvements in clinical activity score, proptosis, and diplopia. In the subacute/chronic phase, the efficacy of methylprednisolone and teprotumumab is reduced. A "critical window" effect was observed, with treatments showing diminished efficacy after 6 months of TED duration. CONCLUSION: This meta-analysis highlights the importance of tailoring treatment strategies based on TED duration, emphasizing early interventions to maximize benefits. The findings guide clinicians in selecting optimal treatments and underscore the need for further research to refine evidence-based approaches, ultimately enhancing patient outcomes and quality of life.
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Oftalmopatía de Graves , Humanos , Corticoesteroides/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/psicología , Calidad de Vida , Resultado del TratamientoRESUMEN
Alzheimer's disease is the leading cause of dementia worldwide and a critical public health problem. While deaths from cardiovascular diseases have decreased, those attributed to Alzheimer's disease have increased in recent years with no curative treatment to date. In this context, effective treatment development has become a global priority. Aducanumab is a human anti-amyloid ß monoclonal antibody approved by the FDA in June 2021 for the treatment of Alzheimer's disease but failed to show the expected clinical efficacy in phase III trials. This review analyzes the history of its controversial acceptance, implications, and prospects for future treatment.
La enfermedad de Alzheimer es la principal causa de demencia en todo el mundo y representa un importante problema de salud pública. Si bien las muertes por enfermedades cardiovasculares han disminuido, las atribuidas a la enfermedad de Alzheimer han aumentado en los últimos años y hasta la fecha no existe tratamiento curativo. Por este motivo, el desarrollo de un tratamiento eficaz se ha convertido en una prioridad mundial. Aducanumab es un anticuerpo monoclonal anti-amiloide ß humano aprobado para el tratamiento de la enfermedad de Alzheimer en junio de 2021 por la FDA, sin la eficacia clínica esperada en los ensayos de fase III. Esta revisión analiza la historia de su controvertida aceptación, implicaciones y perspectivas para el tratamiento futuro.
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Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Aprobación de Drogas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Estados UnidosRESUMEN
We investigated the uptake of nirsevimab for infants and the bivalent respiratory syncytial virus prefusion F (RSVPreF) vaccine for pregnant persons as measures for RSV prevention during an infant's birth hospitalization in a military treatment facility. We found >85% uptake between October 2023 to February 2024. These data may aid health systems plan for future RSV seasons.
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Infecciones por Virus Sincitial Respiratorio , Humanos , Recién Nacido , Infecciones por Virus Sincitial Respiratorio/prevención & control , Femenino , Embarazo , Vacunas contra Virus Sincitial Respiratorio , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Personal Militar , Masculino , Hospitalización/estadística & datos numéricosRESUMEN
INTRODUCTION: Gantenerumab is a monoclonal antibody targeting amyloid ß protein (Aß) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients. METHODS: MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis. RESULTS: A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; p = 0.008569; I2 = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; p = <0.000001; I2 = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; p = <0.000001; I2 = 0%), respectively. DISCUSSION: In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.