Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors

Once-Daily Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults and Adolescents Aged 12 Years and Over: A Short Review of Current Clinical Perspectives

“… 4 , 6 , 9 , 10 In its etiopathogenic complexity, AD derives from T helper 2 (Th2) immune reactions (important in developing the pruritus symptom, due to cytokines, such as IL-4, IL-13 and IL-31); chronic cases of AD, or those found in Asian patients, particularly have a Th17 and Th22 immune profiles. 15 , 16 They are in essence a group of cytoplasmic tyrosine kinases, which aid in mediating the signaling pathways that are cytokine-activated and inhibit them. 10 JAK-1 activity is not only associated with the development of AD but it also plays a role in the pathophysiology of other inflammatory/immunologic skin disorders, such as psoriasis, dermatomyositis, vitiligo, pruritus, lichen sclerosus, granuloma annulare, alopecia areata, sarcoidosis, lichen planus, morphea and, possibly, Multiple Autoimmune Syndrome (MAS).…”

“…Once-daily, orally administered abrocitinib was reported by multiple studies to make possible the selective and reversible inhibition of JAK-1, highlighting its efficacy, good tolerance and positive results in adolescents and adults suffering from moderate-to-severe AD (such as: JADE MONO-1 [NCT03349060]; JADE MONO-2 [NCT03575871]; JADE TEEN [NCT03796676]; JADE COMPARE; GOODERHAM; JADE EXTEND – with not yet available results), in combination with topical therapy or not; 13 , 15 , 24 , 25 it also has the advantage of not exerting effects on JAK2 (by not inhibiting it), significantly lowering the risk of developing anemia and neutropenia. Pruritus, a major AD symptom, improved after neuronal JAK1 pathway inhibition.…”

“…The low frequency of adverse effects and the convenience of having an oral administered drug makes abrocitinib an important additional tool for the treatment of moderate-to-severe forms of AD, besides agents such as dupilumab; thus being said, the data presented stemmed only from clinical trials and the true nature of abrocitinib use will reveal itself only by using it in the real world, with more studies on a higher number of patients, a trait which other systemic treatments such as dupilumab rejoices in. 8 , 15 , 24 …”

Therapie mit Upadacitinib bei schwerem atopischen Ekzem bei Komorbidität einer ankylosierenden Spondylitis und reaktiven Uveitis

“…Dadurch kommt es zur Aktivierung von Januskinasen (JAK), die wiederum STAT (signal transducer and activator of transcription) phosphorylieren, die nun im Zellkern als Transkriptionsfaktoren zahlreicher proinflammatorischer Gene wirken können. Dies befördert die Entzündung der Haut und den Pruritus [6,7].…”

“…Im Oktober 2021 folgte mit Abrocitinib (Cibinqo, selektiver JAK1-Inhibitor) aktuell der dritte Vertreter [14,15]. Unter allen aktuell verfügbaren Therapeutika für die AD zeigen die JAKIs das schnellste Ansprechen des Pruritus [7,16]. Da Upadacitinib seit Januar 2021 auch für die Behandlung der ankylosierenden Spondylitis zugelassen ist, bietet sich diese Therapie für Patienten, die an beiden Erkrankungen leiden, sehr gut an [17].…”