554 The Janus kinase 1 (JAK1) inhibitor PF-04965842 reduces signs and symptoms of moderate to severe atopic dermatitis (AD)

Abstract

Psoriasis (PsO) generates systemic inflammation which may be related to cardiovascular disease (CVD) events. Red cell distribution width (RDW) and mean platelet volume (MPV) appear to be systemic sensors that reflect disordered bone marrow response, and are markers for major adverse cardiac events. We asked whether elevated RDW and/or MPV were related to the risk of CVD events in PsO patients. We performed a retrospective study of psoriasis patients obtained from the Explorys electronic health record database. Psoriasis patients aged 18-65 with available RDW or MPV measurements were included. Patients with diabetes mellitus, Crohns disease, rheumatoid arthritis and generalized atherosclerosis were excluded. Chi-squared test was used for comparisons. Patients with psoriatic arthritis (PsA) were examined independently of PsO patients. A total of 39,510 patients had PsO; 1,920 patients exhibited elevated RDW plus MPV (5%), 7,060 had elevated RDW and normal MPV (18%), and 3,710 had normal RDW and elevated MPV (9%). The incidence of myocardial infarction (MI) was highest among patients with elevated RDW and MPV (OR 3.4, 95% CI 2.7-4.2, p<0.001), followed by patients with high RDW and normal MPV (OR 2.4, 95% CI 2.1-2.8, p<0.001), as compared to normal/low MPV and RDW patients. Atrial fibrillation, coronary artery disease, heart failure and peripheral vascular disease also had elevated OR ranging from 2-8.3, (p<0.001 each) in psoriasis patients with elevated RDW or elevated RDW plus MPV. Among patients with PSA, elevated RDW also increased the risk of an MI with an OR¼1.8, p<0.001. In a cohort of 23 PsO patients followed longitudinally for 1 year, 4 patients had elevated RDW at baseline; among these, 3 patients had a PASI75 response, and RDW was normalized for these responders. Bone marrow sensing of psoriatic inflammation likely alters RDW and MPV responses that are also associated with increased CVD risk.

Treatment of Atopic Dermatitis Using JAK Inhibitors: A Systematic Review

“…The authors' review bridges the gap between previous knowledge and current concepts addressing the use of JAKi in AD. The majority of the studies captured in this review describe Phase I 26,28 or Phase II 27,29 clinical trials. Completed Phase III data is currently unavailable, although multiple adult and paediatric clinical trials studying novel JAKi (including oral baricitinib, topical tofacitinib, and oral upadacitinib) are under way in the USA and Europe.…”

“…Finally, PF-04965842 (oral JAK1/2 inhibitor) and ASN002 (oral dual JAK/ SYK inhibitor) showed promising results in Phase I and Phase II RCT, respectively. 28,29 ASN002 also manifests strong antitumour properties, suppressing haematological malignancies in preclinical studies. 56 Pruritis is a major feature of AD and leads to a significant reduction in QoL, 57 often analogous to the discomfort experienced in chronic pain syndromes.…”

“…A Phase IIb trial was conducted by Gooderham et al 28 to examine the secondary efficacy and safety of PF-04965842, a novel oral JAK1 inhibitor. This double-blind, multicentre RCT followed 323 patients over 12 weeks.…”