For many, many years the standard of care for the initial treatment of graft-versus-host disease is systemic corticosteroids. This treatment has remained a standard of care and has potential significant morbidity. Patients, for example, are at high risk of developing clinically significant infections; among other things they also can develop hyperglycaemia, high blood sugar, they can develop metabolic issues, but we really focussed for the purposes of this study on infectious complications.
What was the study design?
This was, again, a phase II multicentre study, non-inferiority in design, for a primary endpoint of day 28 overall response rate for treatment of GVHD with itacitinib as opposed to systemic corticosteroids in an all-risk patient cohort.
What were your findings?
The key findings were that itacitinib 200mg daily is as effective as systemic corticosteroids for the treatment of acute graft-versus-host disease, both in terms of a primary endpoint of day 28 overall response but also in longer-term outcomes such as survival, NRM, which is non-relapsed mortality, chronic graft-versus-host disease, all the while being safer than systemic corticosteroids with a lower incidence of serious infections and fewer infections per patient when itacitinib monotherapy was used as opposed to systemic corticosteroids for the treatment of low-risk graft-versus-host disease.
What is the clinical impact of these results?
The standard of care has remained the standard of care, systemic corticosteroids, for a very, very long time. What we have shown with this study is that JAK inhibition, itacitinib is a JAK1 inhibitor, holds promise as a potential treatment for graft-versus-host disease and that we can use biomarkers to help select patients for treatment de-escalation and selection of novel treatment paradigms.
In terms of a potential future for this study, because this study showed that itacitinib was as effective and yet safer, it opens the door for potential future studies, potentially larger studies like phase III trials, to demonstrate that this proof of concept works and that the standard of care potentially may be changed.