ABSTRACT
INTRODUCTION: Tofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. MATERIALS AND METHODS: Descriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. RESULTS: Six patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. CONCLUSIONS: Tofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.
ABSTRACT
RESUMEN El transductor de señal Janus-Kinasa y la vía de activación de la transcripción conocida como JAK/STAT es una ruta de señalización principal para la transducción de información en muchas citocinas inflamatorias implicadas durante la sepsis. Se ha demostrado que la vía JAK/STAT está fuertemente relacionada con el fallo multiorgánico, además que muchas citocinas pueden ejercer sus efectos biológicos a través de esta ruta. En los últimos años, se ha logrado un progreso significativo en la comprensión de las funciones de este complejo, sin embargo, su rol en la sepsis como objetivo terapéutico permanece en experimentación. En esta revisión se describen las funciones específicas de la vía JAK/STAT, su rol en la sepsis y presentamos un enfoque traslacional respecto a la perspectiva terapéutica para inhibir esta ruta de señalización durante la sepsis y su interacción con enfermedades inflamatorias como la COVID-19.
ABSTRACT The Janus-Kinase signal transducer and the transcription activation pathway known as JAK /STAT is a major signaling pathway for the transduction of information in many inflammatory cytokines involved during sepsis. The JAK /STAT pathway has been shown to be strongly related to multiorgan failure, and many cytokines can exert their biological effects through this pathway. In recent years, considerable progress has been made in understanding functions of this complex; however, its role in sepsis as a therapeutic target remains under experimentation. This review describes the specific functions of the JAK /STAT pathway, its role in sepsis, and presents a translational approach to the therapeutic perspective aiming to inhibit this signaling pathway during sepsis and its interaction with inflammatory diseases such as COVID-19.
ABSTRACT
The use of Janus kinase (JAK) inhibitors is a new approach in the therapy of inflammatory diseases with immune base. Tofacitinib is one of these inhibitors targeting JAK1 and JAK3, and its efficacy has been demonstrated in the treatment of moderate to severe ulcerative colitis (UC). It is a small synthetic molecule administered orally, with a fast bioavailability and elimination rate, predictable pharmacokinetics and lack of immunogenicity, which are convenient characteristics for both efficacy and safety. This article reviews the pharmacological characteristics of tofacitinib and its safety profile.
Subject(s)
Colitis, Ulcerative/drug therapy , Janus Kinase Inhibitors/pharmacology , Piperidines/pharmacology , Pyrimidines/pharmacology , Arthritis, Rheumatoid , Drug Interactions , Herpes Zoster/chemically induced , Herpes Zoster Vaccine/administration & dosage , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 3/antagonists & inhibitors , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/pharmacokinetics , Neoplasms/immunology , Piperidines/adverse effects , Piperidines/pharmacokinetics , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , Venous Thromboembolism/chemically inducedABSTRACT
RESUMEN La artritis reumatoide (AR) es una enfermedad sistémica que en las últimas décadas ha tenido múltiples opciones terapéuticas. Con la información disponible en la literatura no se recomienda el uso de terapia biológica en pacientes con enfermedad pulmonar difusa, dado que estos medicamentos pueden exacerbar el compromiso pulmonar. Un medicamento de más reciente aparición es el inhibidor de la enzima Janus quinasa, el cual es una opción terapéutica en monoterapia o combinado para pacientes con AR en moderada y alta actividad de la enfermedad, con contraindicación al uso de FARME sintéticos o biológicos, y en pacientes con fallo terapéutico, no obstante, su seguridad a nivel pulmonar no ha sido evaluada en ensayos clínicos y la información disponible es escasa. Describimos el tratamiento, seguimiento y resultados del uso de tofacitinib en 4 pacientes con enfermedad pulmonar secundaria a AR en una serie de casos.
ABSTRACT Rheumatoid arthritis (RA) is a systemic disease for which multiple therapeutic options have been developed in the last decades. Based on the information available in the literature, the use of biological therapy in patients with diffuse lung disease is not recommended because these medications can exacerbate the lung disease. A newer drug is the Janus kinase enzyme inhibitor, which can be used as monotherapy or in combination in patients with moderate to high activity RA, in whom the use of synthetic or biological DMARDs is contraindicated, as well as in patients with therapeutic failure. However, the pulmonary safety of the drug has not been evaluated in clinical trials and the information available is limited. This article discusses the treatment, follow-up, and outcomes of the use of tofacitinib in a series of 4 patients with lung disease secondary to RA.
