Management of Moderate to Severe Plaque Psoriasis with Brodalumab in Daily Practice: Real-World Evidence from the LIBERO Study in the Czech Republic.

INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. METHODS: This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. RESULTS: Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. CONCLUSIONS: LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.

Long-term impact of adalimumab therapy on biomarkers of systemic inflammation in psoriasis: Results of a 2 year study.

Psoriasis patients are at increased risk of atherosclerosis, characterized by endothelial dysfunction, linked through systemic inflammation. Anti-TNF-a therapy seems to decrease this risk. The purpose of this study was to measure the levels of serum markers associated with systemic inflammation in psoriasis patients, compared to healthy individuals and to investigate the change in their levels after 3 months and 2 years of adalimumab therapy. We investigated four biomarkers: high-sensitivity C-reactive protein (hsCRP), oxidized low-density lipoproteins (OxLDL), E-selectin, and Interleukin 22 (IL-22). These markers were measured in healthy volunteers and in 28 patients with moderate/severe psoriasis before and after 3 and 24 months of treatment with adalimumab. Psoriasis patients had increased levels of markers in comparison to the control group. After 3 months of therapy, E-selectin decreased significantly (P < .001), as well as IL-22 (P < .001). hsCRP also decreased but did not show a statistical significance, OxLDL were slightly higher than initially. After 24 months, 17 patients were still being treated with adalimumab. In these patients, hsCRP (P < .05), E-selectin (P < .001) and IL-22 (P < .001) were significantly decreased. OxLDL remained at a higher level. The stable decrease of E-selectin, hsCRP, and IL-22 after 24 months confirms that adalimumab suppresses systemic inflammation.

Psoriasis treatment with adalimumab in clinical practice: long-term experience in a center for biological therapy in the Czech Republic.

BACKGROUND: Adalimumab therapy has an established record of high efficacy in psoriasis treatment. However, only a limited number of studies have investigated long-term results in clinical practice. OBJECTIVES: To evaluate the effectiveness and safety of adalimumab in a center for biological therapy in the Czech Republic. METHODS: Retrospectively, we analyzed 90 patients with moderate to severe psoriasis who were treated with adalimumab between 2008 and 2016. The proportion of patients achieving PASI75, 90, and 100 after 3, 6, 12, 18, 24, 30, and 36 months was determined. RESULTS: The mean period of treatment was 4.4 years (maximum duration reached was 8.6 years). PASI75 was observed in 85.6% of patients after 3 months, PASI90 in 50%, and PASI100 in 23.3%. Throughout the 3-year analysis, PASI90 was persistent in 91.4% and PASI100 in 51.7%. The majority of patients who reached PASI100 showed a trend to maintain the response in the long-term follow-up. No safety issues were identified. CONCLUSIONS: Adalimumab is effective and safe in the long-term treatment of psoriatic patients in daily clinical practice. Once patients achieved PASI100, they tended to remain stable in treatment.

Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: Results of a pilot study.

Psoriasis is a chronic systemic immune-mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti-tumor necrosis factor (TNF)-α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C-reactive protein (measured high sensitively, hsCRP), oxidized low-density lipoproteins (oxLDL), oxLDL/ß-glycoprotein I complex (oxLDL/ß2GPI), vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin and interleukin (IL)-22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL-ß2GPI complex (P < 0.05), E-selectin (P < 0.001) and IL-22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM-1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E-selectin (P < 0.001) and IL-22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF-α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E-selectin and IL-22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.