an2728 and tofacitinib

Psoriasis is a chronic immune-mediated skin disease with a significant impact on patients' quality of life. Mild-to-moderate forms of the disease usually require long-term topical treatment, but prolonged use of corticosteroids and vitamin D analogues is limited by adverse effects. With further understanding of psoriasis pathogenesis, new molecules are emerging aiming to fulfil these clinical needs. Tapinarof, an aryl hydrocarbon receptor modulator, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile. It additionally appears to have a promising remitting effect as patients presented with an average relapsing time of over 3 months. Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects. Roflumilast was evaluated as an option for intertriginous areas with good outcomes in a small sample, but larger trials are required. The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis.

Topics: Administration, Topical; Aminopyridines; Amygdalin; Benzamides; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cyclopropanes; Dermatologic Agents; Humans; Interleukin-2; MicroRNAs; Nitriles; Phosphodiesterase 4 Inhibitors; Piperidines; Psoriasis; Pyrazoles; Pyrimidines; Resorcinols; Stilbenes

Atopic dermatitis (AD) is the most common inflammatory skin disease driven by both terminal keratinocyte differentiation defects and type 2 immune responses, and this condition causes psychological and social morbidity. Although patients with severe AD require systemic immunotherapy, conventional agents including ciclosporin could not be used for several years due to side effects such as nephrotoxicity, hypertension and long-term risks of malignancy. It is well known that dupilumab, which blocks receptor binding of both IL-4 and IL-13, is remarkably efficacious in the treatment of AD. We have entered a new era when many novel topical and systemic agents that may have great potential in AD treatment are emerging through clinical trials. The purpose of this article is to summarize the efficacy and safety of the current topical and systemic therapies in AD by reviewing recently published papers regarding phase II/III clinical trials. It is revealed that topical phosphodiesterase 4 inhibitors and Janus kinase (JAK) inhibitors are promising treatments for AD. Moreover, systemic therapies such as biologics targeting IL-13 and oral JAK inhibitors show strong efficacy in AD.

Topics: Acrylamides; Administration, Topical; Antibodies, Monoclonal, Humanized; Biological Products; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dermatitis, Atopic; Humans; Immunotherapy; Interleukin-13; Janus Kinase Inhibitors; Molecular Targeted Therapy; Phosphodiesterase 4 Inhibitors; Piperidines; Pyridines; Pyrimidines; Pyrroles; Resorcinols; Stilbenes; TRPV Cation Channels

The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Glucocorticoids; Humans; Methotrexate; Mycophenolic Acid; Piperidines; Pyrimidines; Pyrroles; Thalidomide; Ustekinumab