Author(s): Antonio Julià aff1 , Jesús Rodríguez aff2 , José Luis Fernández-Sueiro aff3 , Jordi Gratacós aff4 , Rubén Queiró aff5 , Carlos Montilla aff6 , Juan Carlos Torre-Alonso aff7 , José Javier Pérez-Venegas aff8 , Sara Manrique-Arija aff9 , Santiago Muñoz-Fernández aff10 , Carlos González aff11 , Daniel Roig aff12 , Pedro Zarco aff13 , Alba Erra aff14 , Santos Castañeda aff15 , Alicia García aff16 , Georgina Salvador aff17 , César Díaz-Torne aff18 , Ricardo Blanco aff19 , Alfredo Willisch Domínguez aff20 , José Antonio Mosquera aff21 , Paloma Vela aff22 , Jesús Tornero aff23 , Simón Sánchez-Fernández aff24 , Héctor Corominas aff12 , Julio Ramírez aff25 , Gabriela Ávila aff1 , Arnald Alonso aff1 , Raül Tortosa aff1 , María López-Lasanta aff1 , Juan D Cañete aff25 , Sara Marsal [*] aff1
Keywords:
anti-TNF therapy; genetic marker; psoriatic arthritis; single nucleotide polymorphism; treatment response
Background
Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease characterized by the presence of arthritis together with psoriasis. Originally thought to be a variant of rheumatoid arthritis (RA), PsA is now clearly considered a distinct disease entity [1 ]. The lack of rheumatoid factor, the presence of dactylitis, juxta-articular bone formation, nail dystrophy and a family history of psoriasis are distinctive features of PsA and are actually used as diagnostic criteria for the disease [2 ]. Using these attributes, known as CASPAR criteria, PsA prevalence in psoriasis in large patient cohorts has been recently estimated to be approximately 12-14% [3,4 ].
If inadequately controlled, the activity of PsA leads to the destruction of joints and to disability [5 ]. In order to prevent disease progression, different treatment strategies are actually available [6 ]. From these, the systemic blockade of tumor necrosis factor (TNF) cytokine has proven to be the most effective in the control of moderate-to-severe PsA. Nonetheless, up to 40% of the anti-TNF treated patients do not show a significant clinical response to this therapy [7,8 ]. Given the high cost of these drugs and the possibility of adverse events, there is a need to identify factors that can help predict the response to anti-TNF agents. Clinical variables such as the degree of impairment of physical function, gender and the presence of glucocorticoid treatment have been studied in relation to treatment response [9 ]. However, the ability of these variables to predict anti-TNF response in PsA is very limited and, therefore, new biomarkers must be identified in order to improve treatment decisions [10 ].
Genetic variation has not only been shown to increase the risk of developing the disease, but it has also been shown to increase the risk of developing specific clinical features [4,11 ]. The response to drugs, in particular the response to anti-TNF agents, is a highly relevant clinical feature in PsA that strongly affects the course of the disease. To date, however, very few studies have analyzed the association of genetic variants with the response to anti-TNF therapy in PsA [ 12 ]. The identification of genetic factors associated with anti-TNF response in PsA would therefore be a major step in the management of the disease.
RA is a chronic immune-mediated inflammatory disease that has a similar pathology to...