Ab0102 potential Biomarkers to Predict TNF Inhibitors Outcome in Psoriatic Arthritis

Abstract

BackgroundPsoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease characterized by axial and peripheral arthritis, dactylitis, nail changes and most of the time, is associated with psoriasis. Patients are initially treated with conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), but if they do not respond to these, they are treated with biologics, particularly TNF inhibitors (TNFi) which are common first-line biologics. However, about 40% of patients do not or only partially respond to TNFi. Blood biomarkers predicting response to TNFi would allow patients to be treated earlier with a more appropriate drug [1].ObjectivesWe studied pro- and anti-inflammatory cytokines and adaptive immune cells that could be used as biomarkers for TNFi outcome. Predicting responses to TNFi will help clinicians to choose a more appropriate treatment for patients.MethodsBlood from patients with PsA (n = 8) was analysed before starting TNFi and compared with blood from patients with rheumatoid arthritis (RA) (n = 8). PsA patients were characterised as ‘psoriasis positive’ and ‘psoriasis negative’. Patients were followed at 3 and 6 months after treatment (n = 6). Leukocytes were isolated with Lymphoprep and their phenotype was characterised by CD45, CD3, CD4, CXCR3, CCR6, HLA-DR, CD38, CD25 and CD127. Levels of 12 cytokines in plasma were measured using a cytokine kit (MACSPlex Cytokine 12 Kit, human, Miltenyi Biotec Ltd, UK). Clinical data from patients were collected to determine treatment outcome.ResultsMean level of TNFα was higher in our RA patients (6.2 pg/ml) compared to our PsA patients (4.6 pg/ml). Initial analysis of clinical data suggested that our PsA patients without psoriasis (n = 2) responded better to TNFi than those with active psoriasis (n = 4) at 3 months and 6 months after treatment, with a clear reduction in the number of tender joints (‘psoriasis positive’: 6.65 vs 1.67; ‘psoriasis negative’: 11.5 vs 0.67) and swollen joints (‘psoriasis positive’: 2 vs 0.67; ‘psoriasis negative’: 3.50 vs 0).The mean proportion of activated Th17 cells was higher in our patients with active psoriasis (5.1% of Th17 cells) than those without psoriasis (3.6% of Th17 cells). The mean level of IL-12 and INFγ was higher in the ‘psoriasis positive’ group (respectively 129.2 pg/ml and 266.1 pg/ml) than the ‘psoriasis negative’ group (respectively 52.7 pg/ml and 115 pg/ml).ConclusionWe hypothesize that PsA patients have a lower level of TNFα because of other pro-inflammatory cytokines potentially involved in the inflammatory process. IL-12 can induce IFNγ production by Th1 cells and is involved in the IL12/IL23 axis in psoriasis pathogenesis. IFNγ can induce Th1 and Th17 cells expansion through myeloid dendritic cells activation. In PsA, the high levels of IL-12 and IFNγ involved in psoriasis pathogenesis might be one of the reasons for a poor response to treatment, but larger sample sizes are needed to find a biomarker that could be used routinely by clinicians, and to determine if the same biomarker can also be used for other types of arthritis such as rheumatoid arthritis.Reference[1]Makos A et al., Inflammopharmacol (2022) doi: 10.1007/s10787-022-01092-xAcknowledgementsWe would like to acknowledge the Rheumatology clinical team and research nurses at the RAJH Orthopaedic Hospital, and PsA and RA patients for participating in the study.Disclosure of InterestsNone Declared.