The way type 2 conventional dendritic cells (cDC2) respond to an in vitro test before the patient commences therapy can predict whether the therapy is going to be successful.
Until now it has been difficult to predict how people with psoriasis will respond to the biologic drug adalimumab, which blocks the anti-inflammatory mediator tumor necrosis factor (TNF). Adalimumab, much like other biologics drugs, is effective but not in every patient.
Researchers led by Dr Paola Di Meglio, of the St. Johns Institute of Dermatology at King's, studied blood immune cells of people with psoriasis before and during therapy with adalimumab. They aimed to understand the effect of the drug in the blood, identify the immune cells targeted by it and, ultimately, determine if it is possible to identify any biological feature or biomarker that could tell clinicians in advance if the drug would work in a specific patient.
They found that the way one particular type of white blood cell (cDC2) responded to an in vitro test prior to the commencement of therapy could signal whether the therapy would be successful. Speaking on the potential impact of these findings - released today - Dr Di Meglio said:
We have identified cDC2 as the key mechanistic cellular target of adalimumab influencing and predicting clinical outcome. Further development and prospective validation of this biomarker may result into a companion diagnostic to guide drug selection and benefit patients"– Dr Paola Di Meglio
As no biomarker is currently used in psoriasis to guide drug selection, these psoriasis-related findings have the potential to be useful for other immune mediated inflammatory diseases (IMIDs).
The researchers' next steps involve verifying if cDC2 activation is also a biomarker of response to adalimumab in other immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). Importantly, they hope to develop the in vitro test into a scalable assay that can be used in a clinical setting and, eventually, to test it in a prospective clinical trial.
This study forms part of the UKRI-funded Psoriasis Stratification to Optimize Relevant Therapy (PSORT) Consortium, a UK-wide multicentre partnership involving clinicians, translational researchers, industry and patient groups, at King's, Manchester and Newcastle. PSORT aims to identify determinants of response to biologic therapies, ultimately delivering a patient stratifier algorithm to guide psoriasis management.
Read the full paper Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis by Andres-Ejarque et al in Nature Communications.
