JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases

Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with probably differential underlying physiopathology. Despite the revolutionary era of biologics, some patients remain difficult to treat because of disease severity, drug adverse events, drug allergy or association with severe comorbidities, i.e., uveitis, interstitial lung disease and macrophagic activation syndrome. Janus Kinase (JAK) inhibitors are small molecules that target JAK/Signal Transducers and Activators of Transcription (STAT) pathways, which could then prevent the activity of several proinflammatory cytokines. They may provide a useful alternative in these cases of JIA or in patients actually affected by Mendelian disorders mimicking JIA, such as type I interferonopathies with joint involvement, and might be the bridge for haematopoietic stem cell transplantation in these disabling conditions. As these treatments may have side effects that should not be ignored, ongoing and further controlled studies are still needed to provide data underlying long-term safety considerations in children and delineate subsets of JIA patients that will benefit from these promising treatments.

Juvenile idiopathic arthritis: a limiting disease

“…También puede causar problemas con el desarrollo y crecimiento óseo. (8,9) Según Débora M, la alteración del crecimiento es la complicación más importante de la AIJ, que tiene implicaciones tanto en la salud física como psicosocial. Usualmente en sus etapas iniciales es reversible, mientras que a largo plazo el deterioro de crecimiento da como resultado una estatura baja irreversible estas complicaciones se presentan entre el 1 % y el 17 %, (10) sus causas pueden relacionarse con el grado de inflamación sistémica, el uso de corticosteroides o la nutrición, el apetito puede verse afectado como consecuencia de una enfermedad inflamatoria crónica o como efecto secundario de fármacos con toxicidad gastrointestinal como el metotrexato (MTX).…”

“…(4) En estos casos se debe considerar la introducción temprana de fármacos antirreumáticos modificadores de la enfermedad (bDMARD) biológicos. (8,19) Los fármacos antiinflamatorios no esteroideos (AINE) inhiben las ciclooxigenasas, una enzima necesaria para la síntesis de prostaglandinas. Las funciones fisiológicas de las prostaglandinas son iniciar y mantener la barrera mucosa protectora del estómago y promover el flujo plasmático intrarrenal y el equilibrio electrolítico (20) .…”

Janus Kinase Inhibitors and Interstitial Lung Disease Associated With Pediatric Rheumatic Diseases: An Unexplored Field

“…Tofacitinib and baricitinib were also approved for JIA for children over two years old [16,17]. Clinical trials are ongoing for JAKis, especially tofacitinib, for patients with rheumatic disease, including SLE, type 1 interferonopathies, JDM, SJIA, and polyarticular JIA groups [18][19][20]. JAKis have been shown to be effective for the treatment of RA, either as monotherapy or in combination with methotrexate; however, there is limited literature on their efficacy, safety, and tolerability…”