Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: Focus on Abrocitinib, Baricitinib, and Upadacitinib

Abstract

Atopic dermatitis (AD) is a clinically heterogenous, inflammatory skin condition with a high impact on patients’ daily activities that remains difficult to treat. The knowledge acquired over the last decade on AD pathophysiology and disease burden led to the development of new targeted therapeutic options that enable clinicians to better manage AD patients. The JAK/STAT signaling pathway modulates several immune pathways (T helper (Th)1, Th2, Th17, and Th22 cells) that have been found to be involved in AD pathogenesis. For this reason, JAK inhibitors emerged as a possible therapy for AD. Baricitinib, upadacitinib, and abrocitinib are the three oral JAK inhibitors already approved or in advanced clinical development for this purpose. The results showed that this drug class is highly effective achieving symptomatic relief (itch control) in the short term, as well as improving disease severity in the short and medium term. However, their efficacy should be balanced with possible side effects, that have been reported in clinical trials. More data on the long-term efficacy and safety, as well as from head-to-head comparisons and from real-world setting will be crucial to position oral JAK inhibitors in the AD therapeutic armamentarium.

Efficacy and safety of baricitinib for the treatment of moderate‐to‐severe atopic dermatitis: A systematic review and meta‐analysis of randomized clinical trials

“…strategy. 34 Our results revealed the 4 mg dosage was not always superior to 2 mg in all efficacy outcomes. The most effective dosage may need further studies.…”

“…Baricitinib has been approved by the European Medicines Agency (EMA) for treating moderate‐to‐severe AD in adult patients. The recommended dosage is 4 mg once daily, half dosage schemes (2 mg) may be considered in patients aged 75 years or older, in patients with a history of chronic or recurrent infections, or in those who have achieved a sustained control of disease as a dose tapering strategy 34 . Our results revealed the 4 mg dosage was not always superior to 2 mg in all efficacy outcomes.…”

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases

“…Symptom treatment of mild forms of atopic dermatitis is currently carried out with emollients and low potency topical steroids, while severe types are treated with oral corticosteroids, cyclosporine (for review see [ 249 ]) and other immunosuppressants such as azathioprine [ 250 ], methotrexate [ 251 , 252 ] and the calcineurin inhibitors tacrolimus and pimecrolimus, which were approved as topical treatment options for atopic dermatitis about two decades ago [ 253 ]. An important biologic for the treatment of atopic dermatitis is dupilumab, an IL-4 receptor-α inhibitor that blocks both IL-4 and IL-13 activity and is approved for the treatment of moderate-to-severe atopic dermatitis in patients 6 years of age and older (for review see [ 254 ]). Other biologics currently under investigation for the treatment of atopic dermatitis include the IL-13 inhibitors lebrikizumab and tralokinumab [ 255 ], with the latter agent now approved in Europe.…”

“…A further therapeutic strategy is the use of crisaborole, a topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis [ 258 ], which is superior even to topical immunomodulators such as tacrolimus and pimecrolimus [ 259 ]. Since the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathway is associated with the development of atopic dermatitis, inhibitors of this pathway have been discovered as a possible pharmacotherapeutic option, of which baricitinib has been approved by the EMA for moderate-to-severe atopic dermatitis in adult patients (for review see [ 254 ]). A small molecule JAK1 inhibitor approved by the EMA for the treatment of moderate-to-severe atopic dermatitis in patients 12 years of age and older is upadacitinib, which recently showed a faster onset of action than dupilumab in a phase III study [ 260 ].…”

Dupilumab-Associated Head and Neck Dermatitis With Ocular Involvement in a Ten-Year-Old With Atopic Dermatitis: A Case Report and Review of the Literature

“…The American Academy of Dermatology recommends treating AD with non-pharmacologic interventions (e.g., moisturizers, appropriate bathing practices), topical pharmacological preparations (e.g., corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors), and phototherapy if necessary and available [ 3 - 5 ]. Historically, systemic therapies (e.g., cyclosporine, azathioprine, methotrexate, mycophenolate mofetil) have been reserved for moderate to severe pediatric AD refractory to standard therapies [ 6 , 7 ]. However, these medications were used off-label and required laboratory monitoring, had unfavorable side effect profiles, and resulted in high recurrence rates, as in the case of oral prednisone.…”