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Summary: Background: Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers. Objectives: To evaluate the efficacy and safety of secukinumab 300 mg in HLA‐Cw6‐positive (Cw6‐POS) and HLA‐Cw6‐negative (Cw6‐NEG) patients with moderate‐to‐severe chronic plaque‐type psoriasis. Methods: SUPREME was a 24‐week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks. Results: In total, 434 patients were recruited: 185 (42·6%) were Cw6‐POS and 246 (56·7%) were Cw6‐NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6‐POS 42·7 ± 13·1; Cw6‐NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6‐POS 20·7 ± 8·99; Cw6‐NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6‐POS and 79·7% of Cw6‐NEG patients (difference 0·76; 95% confidence interval −7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6‐POS 1·36 ± 3·58; Cw6‐NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment‐emergent adverse events [Cw6‐POS 42·7%; Cw6‐NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI. Conclusions: Determination of HLA‐Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA‐Cw6 status. What's already known about this topic? HLA‐Cw6 is associated with the phenotypic features of psoriasis and positive response to ustekinumab and is present in approximately 40–80% of cases.Secukinumab is a fully human monoclonal antibody neutralizing interleukin‐17A and it has demonstrated a rapid onset of action and sustained responses with a favourable safety profile in moderate‐to‐severe psoriasis, psoriatic arthritis and ankylosing spondylitis. What does this study add? Although HLA‐Cw6‐positive and HLA‐Cw6‐negative patients have distinct clinical features, the present study showed that secukinumab achieved similar clinical responses in both cohorts after 24 weeks of treatment.There was no difference in efficacy regarding HLA‐Cw6 status. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is a chronic-relapsing disease. It is defined as a LE localized to the skin without any significant systemic symptoms. Its annual incidence is of 4 cases per 100,000 persons with a prevalence of 73 cases per 100,000 persons. The etiology is unknown but it is considered as a prototype of autoimmune disease in which genetic factors (HLA), environmental factors (photo exposure and cigarette smoking) and pharmacological agents play an important role. The most accepted classification includes three clinical variants: acute (ACLE), subacute (SCLE) and chronic (CCLE). A fourth variety is the intermittent form (ICLE) also called "lupus tumidus" (LET) which is considered by some authors a distinct form from CCLE. The skin lesions are subdivided into LE specific and LE non-specific. The latter have a considerable importance as a symptom of evolution of the disease towards a systemic form of lupus (SLE). The histopathology of CLE is characterized by an interface dermatitis with vacuolization of the basal layer, a predominantly lymphocytic, perivascular and periadnexal infiltrate, epidermal and follicular hyperkeratosis, deposit of positive PAS material at the dermo-epidermal junction leading to atrophic-cicatricial evolution. Depending on the clinical variants, these microscopic features are more or less evident and are associated with peculiarities such as deposits of mucin (SCLE and LET), involvement of the panniculus in LE panniculitis, disappearance of the adnexa (cicatricial alopecia). The relationship between SLE/CLE is still under study: the progression of CLE in SLE is reported in a variable percentage of cases ranging from 12 to 18%. CLE therapy is aimed at preventing recurrences and scarring outcomes. Photoprotection with clothing, chemical and physical sunscreens active on UVA and UVB radiations is very important. Topical therapy is based on the use of steroids and calcineurin inhibitors, while the systemic therapy includes hydroxychloroquine as the first drug of choice.