Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA (Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated with Secukinumab) was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomly assigned to receive 300 mg or 150 mg secukinumab until week 52 or to receive placebo until week 12 and then 300 mg or 150 mg secukinumab until week 52. The primary outcome was endothelial function measured by flow-mediated dilation (FMD). Baseline FMD was significantly lower in psoriasis patients than healthy volunteers (4.4 AE 3.9% vs. 6.1 AE 3.3%, P ¼ 0.01). At week 12, baseline-adjusted mean FMD was numerically higher in patients receiving secukinumab versus those receiving placebo, but this difference (300-mg group, þ1.2%; 150-mg group, þ0.76%; P ¼ 0.223 and P ¼ 0.403 by analysis of covariance) did not reach significance. At week 52, FMD increased across groups. FMD was significantly higher than baseline in patients receiving the label dose of 300 mg secukinumab for 52 weeks (þ2.1%, 95% confidence interval ¼ 0.8e3.3; P ¼ 0.0022). Other relevant CV markers were unchanged. CARIMA indicates that secukinumab might have a beneficial effect on CV risk by improving the endothelial function of patients with plaque psoriasis.

In 2 double-blind studies, ambulatory patients with objectively proven, disseminated metastatic breast carcinoma (TOPIC-1) or stage III/IV non-small-cell lung carcinoma (TOPIC-2) were randomized to certoparin 3000 IU or placebo subcutaneously once daily, for 6 months. Primary efficacy outcome was objectively confirmed symptomatic or asymptomatic venous thromboembolism (VTE). Safety outcomes included bleeding (major and minor), and thrombocytopenia. TOPIC-1 was halted after an interim analysis. Venous thromboembolism occurrence was not different between treatment groups in TOPIC-1 (4% treated with certoparin, 7 of 174 vs 4% receiving placebo, 7 of 177, odds ratio [OR] 1.02; 95% confidence interval [CI] 0.30-3.48) and in TOPIC-2 (4.5%, 12 of 268) vs 8.3%, 22 of 264, respectively, OR 0.52; CI 0.23-1.12). Mortality was not different between groups. A post hoc analysis showed certoparin significantly reduced VTE in stage IV lung carcinoma (3.5% vs 10.2%; P = .032) without increased bleeding. In conclusion, thrombosis risk and prophylactic benefit was highest in stage IV lung carcinoma patients.

SummaryBackground Secukinumab is a fully human antibody that neutralizes interleukin-17A. It has significant efficacy and a favourable safety profile in moderate-tosevere plaque psoriasis and psoriatic arthritis. Objectives To compare secukinumab with fumaric acid esters (FAEs) in a randomized controlled trial. Methods In this 24-week, randomized, open-label, multicentre study with blinded assessment, patients with moderate-to-severe plaque psoriasis, naive to systemic treatments, were randomized to receive secukinumab 300 mg subcutaneously or oral FAEs. The primary end point was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75 response) at week 24, and missing patients were considered responders if they were responders at the time of dropout. Results In total 202 patients were randomized and 200 were treated with at least one dose. Outcomes at week 24 were available for 147 and imputed for 53 patients. Discontinuations were mostly due to adverse events, which occurred more frequently in the FAE group (1Á9% vs. 33Á0%). At week 24, significantly more patients receiving secukinumab compared with FAEs achieved PASI 75 response (89Á5% vs. 33Á7%, P < 0Á001), PASI 90 response (81Á0% vs. 28Á4%, P < 0Á001) and Dermatology Life Quality Index 0 or 1 response (71Á4% vs. 25Á3%, P < 0Á001). Conclusions Secukinumab demonstrated superior efficacy to FAEs in patients with psoriasis over a 24-week period.

Background Secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate‐to‐severe psoriasis. Trial protocols specify transition periods and prohibit concomitant psoriasis medication. Data are therefore needed on secukinumab effectiveness and safety in routine clinical practice. Objectives The PROSPECT study assesses prior and concomitant psoriasis treatments and transition periods in subjects receiving secukinumab. Here, we report interim effectiveness and safety data for secukinumab in the context of prior and concomitant treatments. Methods PROSPECT is an ongoing 24‐week, single‐cohort, non‐interventional study. Subjects with moderate‐to‐severe psoriasis with a decision to receive secukinumab 300 mg were included. Results Of 1988 subjects, 1238/1988 (62.4%) were male, and mean age was 48.1 ± 13.7 years. Mean baseline Psoriasis Area and Severity Index (PASI) score was 17.7 ± 12.5. 90.9% of subjects had prior systemic treatment. Concomitant treatment was recorded in 44.3% of subjects. Median duration of transition period was 14.0, 30.0 and 44.5 days from prior topical, conventional systemic and biologic treatments. At Week 24, PASI75/90/100 was reached by 86.1%, 68.5% and 39.7% of subjects who started secukinumab treatment at baseline. No unexpected safety signals were observed. Conclusion PROSPECT provides a large prospective real‐world analysis of secukinumab treatment and includes prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real‐world setting. Secukinumab effectiveness and safety were comparable to that seen in the phase 2/3 secukinumab clinical trial programme.

PROSPECT is the first study to investigate prior and concomitant use of psoriasis treatments in subjects receiving secukinumab in a real-world setting. The majority of the subjects had a high disease burden and use of concomitant treatment increased with disease severity. The duration of the transition period depended on prior treatment.