Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders / Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with Pubmed and Google Scholar from January 2000 to January 2023, using the keywords “Janus kinase inhibitors”, “JAK inhibitors”, “off-label”, “dermatology”, “safety”, “adverse events”, “ruxolitinib”, “upadacitinib”, “abrocitinib” and “baricitinib”. Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders (AU)

Los inhibidores de JAK actúan bloqueando la acción de ciertas citoquinas inflamatorias involucradas en varias enfermedades inflamatorias. Cuatro moléculas han sido aprobadas para uso en dermatología: upadacitinib, baricitinib, abrocitinib y ruxolitinib tópico. Se han reportado usos fuera de indicación para diferentes enfermedades dermatológicas. Se realizó una revisión narrativa de la literatura sobre la seguridad a largo plazo de los inhibidores de JAK aprobados en dermatología y su uso fuera de indicación en enfermedades dermatológicas, mediante búsquedas bibliográficas en Pubmed y Google Scholar desde enero de 2000 hasta enero de 2023, incluyendo las palabras clave: «Janus kinase inhibitors», «JAK inhibitors», «off-label», «dermatology», «safety», «adverse events», «ruxolitinib», «upadacitinib», «abrocitinib» y «baricitinib». Se encontraron un total de 37 trastornos dermatológicos con estudios que respaldan el uso de estos fármacos. Los estudios preliminares indican que los inhibidores de JAK tienen un perfil de seguridad generalmente favorable y pueden considerarse una opción en muchas enfermedades dermatológicas (AU)

[Artículo traducido] Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología / Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders

Los inhibidores de JAK actúan bloqueando la acción de ciertas citoquinas inflamatorias involucradas en varias enfermedades inflamatorias. Cuatro moléculas han sido aprobadas para uso en dermatología: upadacitinib, baricitinib, abrocitinib y ruxolitinib tópico. Se han reportado usos fuera de indicación para diferentes enfermedades dermatológicas. Se realizó una revisión narrativa de la literatura sobre la seguridad a largo plazo de los inhibidores de JAK aprobados en dermatología y su uso fuera de indicación en enfermedades dermatológicas, mediante búsquedas bibliográficas en Pubmed y Google Scholar desde enero de 2000 hasta enero de 2023, incluyendo las palabras clave: «Janus kinase inhibitors», «JAK inhibitors», «off-label», «dermatology», «safety», «adverse events», «ruxolitinib», «upadacitinib», «abrocitinib» y «baricitinib». Se encontraron un total de 37 trastornos dermatológicos con estudios que respaldan el uso de estos fármacos. Los estudios preliminares indican que los inhibidores de JAK tienen un perfil de seguridad generalmente favorable y pueden considerarse una opción en muchas enfermedades dermatológicas (AU)

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with Pubmed and Google Scholar from January 2000 to January 2023, using the keywords “Janus kinase inhibitors”, “JAK inhibitors”, “off-label”, “dermatology”, “safety”, “adverse events”, “ruxolitinib”, “upadacitinib”, “abrocitinib” and “baricitinib”. Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders (AU)

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. / [Artículo traducido] Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología.

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with PubMed and Google Scholar from January 2000 to January 2023, using the keywords "Janus kinase inhibitors", "JAK inhibitors","off-label", "dermatology", "safety", "adverse events", "ruxolitinib", "upadacitinib","abrocitinib" and "baricitinib". Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders.

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders.

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with Pubmed and Google Scholar from January 2000 to January 2023, using the keywords "Janus kinase inhibitors", "JAK inhibitors", "off-label", "dermatology", "safety", "adverse events", "ruxolitinib", "upadacitinib", "abrocitinib" and "baricitinib". Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders.

BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados / BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings

Antecedentes En los últimos años se ha producido una revolución en el conocimiento de la dermatitis atópica (DA) que ha revertido en un salto cualitativo en las expectativas terapéuticas. En este contexto, resulta fundamental disponer de datos de práctica clínica de calidad. Material y método BIOBADATOP es el Registro Español de Dermatitis Atópica, un estudio observacional, prospectivo y multicéntrico, con una cohorte de pacientes de cualquier edad con DA que requieren el empleo de tratamiento sistémico (convencional o innovador). Se registraron los datos demográficos, de diagnóstico, los tratamientos y los acontecimientos adversos (AA). Resultados Se incluyeron 258 pacientes, con 347 tratamientos sistémicos iniciados para la DA. Se suspendieron el 29,4% de los tratamientos, principalmente por falta de eficacia (10,7%). Durante el período de seguimiento se registraron 132AA. Del total, el 65% (86) relacionaron con el tratamiento sistémico iniciado, siendo los más frecuentes dupilumab (39AA) y ciclosporina (38AA). Los AA más frecuentes fueron: conjuntivitis (11pacientes), cefalea (6), hipertricosis (5) y náuseas (4). Se registró un AA grave (mastoiditis aguda) relacionado con ciclosporina. Conclusiones En este primer informe, la descripción de AA está limitada por los cortos períodos de seguimiento, que no permiten el cálculo de tasas de incidencias crudas ni ajustadas y no se han realizado comparaciones. Hasta la fecha del análisis no se han registrado AA graves en relación a las nuevas terapias. BIOBADATOP permitirá generar conocimiento en términos de efectividad y seguridad de los tratamientos sistémicos clásicos y las nuevas terapias en DA (AU)

Background In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. Materials and method The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). Results We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. Conclusions Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD (AU)

[Translated article] BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings / BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados

Background In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. Materials and method The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). Results We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. Conclusions Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD (AU)

Antecedentes En los últimos años se ha producido una revolución en el conocimiento de la dermatitis atópica (DA) que ha revertido en un salto cualitativo en las expectativas terapéuticas. En este contexto, resulta fundamental disponer de datos de práctica clínica de calidad. Material y método BIOBADATOP es el Registro Español de Dermatitis Atópica, un estudio observacional, prospectivo y multicéntrico, con una cohorte de pacientes de cualquier edad con DA que requieren el empleo de tratamiento sistémico (convencional o innovador). Se registraron los datos demográficos, de diagnóstico, los tratamientos y los acontecimientos adversos (AA). Resultados Se incluyeron 258 pacientes, con 347 tratamientos sistémicos iniciados para la DA. Se suspendieron el 29,4% de los tratamientos, principalmente por falta de eficacia (10,7%). Durante el período de seguimiento se registraron 132AA. Del total, el 65% (86) relacionaron con el tratamiento sistémico iniciado, siendo los más frecuentes dupilumab (39AA) y ciclosporina (38AA). Los AA más frecuentes fueron: conjuntivitis (11pacientes), cefalea (6), hipertricosis (5) y náuseas (4). Se registró un AA grave (mastoiditis aguda) relacionado con ciclosporina. Conclusiones En este primer informe, la descripción de AA está limitada por los cortos períodos de seguimiento, que no permiten el cálculo de tasas de incidencias crudas ni ajustadas y no se han realizado comparaciones. Hasta la fecha del análisis no se han registrado AA graves en relación a las nuevas terapias. BIOBADATOP permitirá generar conocimiento en términos de efectividad y seguridad de los tratamientos sistémicos clásicos y las nuevas terapias en DA (AU)

BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings. / BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados.

BACKGROUND: In recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. MATERIALS AND METHOD: The Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). RESULTS: We studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. CONCLUSIONS: Initial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Updated Review on Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic or chronically recurrent Inflammatory dermatosis associated with multiple triggers that has a complex pathophysiological mechanism. It is characterized by a heterogeneous clinical expression, signs, and symptoms. Its etiology and pathogenesis are complex and are influenced by multiple immune-mediated factors. Treatment of AD can also be complex, given the high number of available drugs and multiple therapeutic targets. In this review, we summarize current literature on the efficacy and safety of topical and systemic drugs to treat moderate-to-severe AD. We begin with topical treatments such as corticosteroids and calcineurin inhibitors and subsequently address the latest systemic treatments, such as Janus kinase inhibitors (upadacitinib, baricitinib, abrocitinib, gusacitinib) and interleukin (IL) inhibitors, which have proven efficacious in AD, namely, dupilumab (IL-4 and IL-13), tralokinumab (IL-13), lebrikizumab (IL-13), and nemolizumab (IL-31). Given the large number of drugs available, we summarize the pivotal clinical trials for each drug, evaluate recent real-world experience in terms of safety and efficacy for purposes of compilation, and provide evidence to guide the optimal choice of therapy (AU)

La dermatitis atópica (DA) es una dermatosis inflamatoria crónica o crónicamente recurrente, asociada a múltiples desencadenantes y con un mecanismo fisiopatológico complejo. Se caracteriza por una expresión clínica, signos y síntomas heterogéneos. Su etiopatogenia es compleja y está influenciada por múltiples factores inmunomediados. El tratamiento de la DA también resulta complejo; esto se debe a que existen varios fármacos que pueden utilizarse para tratar la DA con múltiples dianas terapéuticas. En esta revisión, resumimos la literatura actual sobre la eficacia y seguridad de los fármacos tópicos y sistémicos para tratar la DA de moderada a grave. Partiremos desde tratamientos tópicos como los corticoides y los inhibidores de la calcineurina tópicos, hasta los últimos tratamientos sistémicos como los inhibidores cinasas Jano JAK (upadacitinib, baricitinib, abrocitinib, gusacitinib) y los inhibidores de la interleucina (IL) que han demostrado eficacia sobre la DA: dupilumab (IL-4 e IL-13), tralokinumab (IL-13), lebrikizumab (IL-13) y nemolizumab (IL-31). Como hemos visto existen multitud de fármacos para tratar la DA, por este motivo hemos realizado una revisión en la cual se han tenido en cuenta todos los ensayos clínicos de fase III de cada fármaco. También ha sido evaluada su experiencia reciente en la práctica clínica en concepto de seguridad y eficacia con el propósito de compilar esta evidencia para ayudar a seleccionar la terapia adecuada (AU)

Inhibidores de receptores JAK quinasa e infección por virus varicela zoster en pacientes con artritis reumatoide. Revisión sistemática de la literatura / JAK Kinase Inhibitors and Varicella Zoster Virus Infection in Patients with Rheumatoid Arthritis. Systematic Review of the Literature

Objetivos: El objetivo de esta revisión sistemática es evaluar la infección por herpes zoster (HZ) publicada en los ensayos clínicos faseII y faseIII de pacientes con AR en tratamiento con inhibidores de JAK (iJAK). Material y métodos: Revisión sistemática de la literatura que evalúa la incidencia de HZ publicada en los ensayos clínicos de los distintos iJAK comercializados o en estudio. Resultados: Las tasas de HZ variaron entre el 1,51 y 20,22. Los resultados se expresaron principalmente en porcentaje de eventos. Los estudios más recientes categorizaron mejor la incidencia de HZ y su gravedad. Conclusión: Los iJAK se asocian a mayor riesgo de HZ. Aunque las tasas de HZ de los iJAK selectivos de JAK1 son menores, son necesarios más estudios que confirmen estos resultados.(AU)

Objectives: JAK kinase inhibitors (JAKi) are a new therapeutic option in the treatment of rheumatoid arthritis, but they are not without risks, especially the incidence of herpes zoster (HZ). Material and methods: Systematic literature review that evaluates the incidence of HZ published in the clinical trials of the different JAKis marketed or under study. Results: The HZ rates ranged between 1.51 and 20.22. The results were expressed mainly as a percentage of events. The most recent studies better categorized the incidence of HZ and its severity. Conclusion: JAKis are associated with an increased risk of HZ. Although the HZ rates of the selective JAK1 JAKis are lower, more studies are needed to confirm these results.(AU)

JAK kinase inhibitors and varicella zoster virus infection in patients with rheumatoid arthritis. Systematic review of the literature.

OBJECTIVES: JAK kinase inhibitors (JAKi) are a new therapeutic option in the treatment of rheumatoid arthritis, but they are not without risks, especially the incidence of herpes zoster (HZ). MATERIAL AND METHODS: Systematic literature review that evaluates the incidence of HZ published in the clinical trials of the different JAK is marketed or under study. RESULTS: The HZ rates ranged between 1.51 and 20.22. The results were expressed mainly as a percentage of events. The most recent studies better categorized the incidence of HZ and its severity. CONCLUSION: JAK is are associated with an increased risk of HZ. Although the HZ rates of the selective JAK1 JAK is are lower, more studies are needed to confirm these results.

Inhibidores de JAK: usos en dermatología. Parte 2: aplicaciones en psoriasis, dermatitis atópica y otras dermatosis / Janus Kinase Inhibitors in Dermatology: Part 2: Applications in Psoriasis, Atopic Dermatitis, and Other Dermatoses

La vía de señalización de citocinas Janus cinasa/transductor de señal y activador de transcripción (JAK/STAT) es un área de interés emergente en dermatología, con evidencia creciente del papel clave en la patogénesis de las enfermedades inflamatorias cutáneas. Debido a que algunas citocinas proinflamatorias usan la vía JAK/STAT para la transducción de señales se convierte en una diana terapéutica prometedora para el tratamiento de dichas enfermedades al modular de forma selectiva el sistema inmune. El objetivo de esta revisión es conocer la vía de señalización JAK/STAT y su papel en distintas enfermedades dermatológicas inmunomediadas. En esta segunda parte, se revisará la eficacia y seguridad de los inhibidores de JAK –en formulación oral o tópica– para el tratamiento de la psoriasis, la dermatitis atópica y otras dermatosis (AU)

Dermatologists’ interest in the Janus-associated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been growing as evidence builds to support its key role in the pathogenesis of inflammatory skin diseases. Because certain proinflammatory cytokines use the JAK/STAT pathway for signal transduction, it has become a promising therapeutic target in diseases where selective modulation of the immune system can be useful. We aim to review current knowledge of the JAK/STAT signaling pathway and its role in immune-mediated skin diseases. In the second part of the review we cover the efficacy and safety of oral and topical JAK inhibitors in the treatment of psoriasis, atopic dermatitis, and other skin diseases (AU)

Inhibidores de JAK: usos en dermatología. Parte 1: generalidades, aplicaciones en vitíligo y en alopecia areata / Janus Kinase Inhibitors in Dermatology: Part 1 — General Considerations and Applications in Vitiligo and Alopecia Areata

La vía de señalización de citocinas Janus cinasa/transductor de señal y activador de transcripción (JAK/STAT) es un área de interés emergente en dermatología, con evidencia creciente del papel clave en la patogénesis de las enfermedades inflamatorias cutáneas. Debido a que algunas citocinas proinflamatorias usan la vía JAK/STAT para la transducción de señales, esta se convierte en una diana terapéutica prometedora para el tratamiento de dichas enfermedades, al modular de forma selectiva el sistema inmune. El objetivo de esta revisión es conocer la vía de señalización JAK/STAT y su papel en distintas enfermedades dermatológicas inmunomediadas. En esta primera parte, se revisará la eficacia y seguridad de los inhibidores de JAK –en formulación oral o tópica– para el tratamiento del vitíligo y la alopecia areata (AU)

Dermatologists’ interest in the Janus-associated kinase/signal transducers and activators of transcription (JAK/STAT) pathway has been growing as evidence builds to support its key role in the pathogenesis of inflammatory skin diseases. Because certain proinflammatory cytokines use the JAK/STAT pathway for signal transduction, it has become a promising therapeutic target in diseases where selective modulation of the immune system can be useful. We aim to review current knowledge of the JAK/STAT signaling pathway and its role in immune-mediated skin diseases. In the first part of the review we cover the efficacy and safety of oral and topical JAK inhibitors in the treatment of vitiligo and alopecia areata (AU)

Janus Kinase Inhibitors in Dermatology: Part 2: Applications in Psoriasis, Atopic Dermatitis, and Other Dermatoses.

Dermatologists' interest in the Janus-associated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been growing as evidence builds to support its key role in the pathogenesis of inflammatory skin diseases. Because certain proinflammatory cytokines use the JAK/STAT pathway for signal transduction, it has become a promising therapeutic target in diseases where selective modulation of the immune system can be useful. We aim to review current knowledge of the JAK/STAT signaling pathway and its role in immune-mediated skin diseases. In the second part of the review we cover the efficacy and safety of oral and topical JAK inhibitors in the treatment of psoriasis, atopic dermatitis, and other skin diseases.

[JAK2 inhibitors]. / Inhibidores de JAK2.

Pharmacological inhibition of the kinase activity of JAK proteins can interfere with the signaling of immunomodulatory cytokines and block the constitutive activation of the JAK-STAT pathway that characterizes certain malignancies, including chronic myeloproliferative neoplasms. JAK inhibitors may, therefore, be useful to treat malignancies as well as inflammatory or immune disorders. Currently, the most significant advances have been made in the treatment of myelofibrosis, where these drugs may lead to a remarkable improvement in the control of hyperproliferative manifestations. However, available data suggest that this treatment is not curative of myelofibrosis. In general, JAK2 inhibition induces cytopaenias, with this being considered a class side-effect. By contrast, the extrahaematologic toxicity profile varies significantly among the different JAK inhibitors. At present, there are several clinical trials evaluating the combination of ruxolitinib with other drugs, in order to improve its therapeutic activity as well as reducing haematologic toxicity.