The HLA-Cw6 Dilemma: Is It Really an Outcome Predictor in Psoriasis Patients under Biologic Therapy? A Monocentric Retrospective Analysis

Abstract

HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. Data regarding correlation between HLA-Cw6 status and biologic treatment outcomes are divergent. The aim of our study in our cohort of psoriatic patients was to explore if the HLA-Cw6 status influences the response rate to biologic therapies at 16 and 48 weeks. One hundred and one psoriatic patients eligible for biologic therapies were enrolled. HLA-C*06 alleles were detected from their blood samples. The effectiveness of antipsoriatic treatments was reported as 90% Psoriasis Area and Severity Index reduction (PASI90). All biologics showed efficacy at week 16, without significant differences between one another. HLA-Cw6 status did not seem to affect baseline characteristics, or treatment response at week 16. At week 48, IL-12/23 and IL-17 targeting drugs were more effective on Cw6-positive patients than on Cw6-negative patients. Conversely, TNF-targeting drugs seemed to be more effective on Cw6- negative patients than on Cw6-positive patients. The HLA-Cw6 test could well deserve to be integrated into the clinical laboratory work-up supporting the choice of the correct biologic.

HLA-Cw1 and Psoriasis

“…Patients with psoriatic arthritis with HLA-Cw6 positivity more often have an early onset, and their cutaneous symptoms often develop before arthritis [7]. HLA-Cw6-positive patients have been shown in several studies to be more responsive to methotrexate [44,45], anti-interleukin (IL)-12/23 [46,47], anti-IL-17 [48,49] and IL-23 drugs [50]. However, inconsistent data were reported in patients receiving secukinumab [51].…”

“…However, inconsistent data were reported in patients receiving secukinumab [51]. Moreover, anti-tumor necrosis factor agents showed less efficacy in patients with HLA-Cw6-positive psoriasis [48]. In comparison, HLA-Cw1-B46 carriers were reported to be clinically distinct, showing a lower risk of disease, greater nail involvement, and a later age at onset [12].…”

Novel concepts in psoriasis: histopathology and markers related to modern treatment approaches

“…The effect of IL-23 in psoriasis is considered to be the consequence of its effect on IL-17, an important cytokine with a role in the cascade of inflammation [ 72 ]. The most important biological therapies used nowadays in psoriasis, as well as their site of action, are presented in Table 4 [ 37 , 73 , 74 , 75 , 76 ].…”

“…One major pathological factor is represented by HLA-Cw6 , which is considered to be highly associated with psoriasis susceptibility alleles. This review aims to state the possible connection between the level of HLA-Cw6 and the response to different types of biological agents [ 74 ].…”

“…Last but not least, patients with a moderate PASI score were treated with anti-TNF- α agents, such as Adalimumab, Etanercept, Infliximab). The response to treatment showed yet no link between the base level of HLA-Cw6 and the maintenance of PASI90 after being reached at week 16, which suggested that HLA-Cw6 status could not be considered an “overall prognostic factor” [ 74 ]. On the other hand, when taken into consideration separately, drugs targeting IL-12/IL-23 and IL-17 showed a better response in those with an HLA-Cw6 positive (POS) status, while drugs targeting TNF- α were opposingly showing more efficiency on those with an HLA-Cw6 negative (NEG) status [ 81 , 82 ].…”