Publications

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombinant enzymes and primary human lymphocytes to assess the JAK1 specificity of itacitinib and study inhibition of STAT signalling. Itacitinib was a selective JAK 1 inhibitor and demonstrated 22, >600, and 256 fold selectivity over JAK2, JAK3 and TYK2, respectively. Furthermore, they demonstrated that itacitinib led to inactivation of STATs and subsequently impairing IL-2 induced cell proliferation. Oral administration in mice demonstrated Itacitinib be orally bioavailable in a non proportional dose dependent manner. In a rat adjuvant induced arthritis model, once daily itacitinib treatment inhibited disease progression at doses of 10 and 30 mg/kg and increase itacitinib dose showed reduction of joint inflammation, pannus formation, cartilage damage and total ankle histopathology.This is the first report of itacitinib as a potent and selective JAK1 inhibitor with anti-inflammatory activity across disease models, and indicates that itacitinib could be a potential treatment for inflammatory diseases.