Izokibep for the treatment of moderate-to-severe plaque psoriasis: a phase II, randomized, placebo-controlled, double-blind, dose-finding multicentre study including long-term treatment.

BACKGROUND: Monoclonal antibodies to interleukin (IL)-17 have shown strong efficacy in patients with psoriasis. Izokibep is a unique IL-17A inhibitor with a small molecular size and favourable distribution to sites of inflammation. OBJECTIVES: To evaluate the dose response, efficacy and safety of izokibep in patients with plaque psoriasis. METHODS: In this double-blind, randomized, phase II dose-finding study (AFFIRM-35) in adults with moderate-to-severe plaque psoriasis and inadequate response to two or more standard therapies, patients were randomized (1:1:1:1:1) to placebo or izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks. During the remainder of the 52-week core study, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. The core study was followed by two optional consecutive 1-year extension periods for a total duration of 3 years. The primary endpoint was a 90% reduction in PASI score (PASI 90) at week 12. Additional efficacy outcomes and adverse event (AE) rates were evaluated. RESULTS: In total, 109 patients were randomized [safety set, n = 108 (one exclusion criteria failure); full analysis set, n = 106]. At week 12, PASI 90 response rates were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively. Rapid dose-dependent improvements were also observed across other efficacy outcomes. During the placebo-controlled period, AEs in the izokibep groups were similar to placebo except for mild injection site reactions. AEs were generally mild to moderate and the drug was well tolerated. Izokibep maintained efficacy at the higher dosage groups for up to 3 years, with no new safety signals. CONCLUSIONS: Data from this phase II study indicate that izokibep is well tolerated and efficacious in the treatment of plaque psoriasis. Higher doses or more frequent dosing could be explored to further enhance response rates.

Topical long-term therapy of psoriasis with vitamin D3 analogues, corticosteroids and their two compound formulations: position paper on evidence and use in daily practice.

BACKGROUND: Current data from daily practice show that vitamin D3 analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long-term treatment of psoriasis. AIM: To evaluate scientific evidence about topical long-term therapy with vitamin D3 analogues, corticosteroids and their two-compound-products in psoriasis vulgaris and scalp psoriasis and to develop daily practice recommendations. METHODS: Systematic literature review via PubMed and Embase and informal expert consensus. RESULTS: The search strategy identified 21 relevant clinical trials. Best evidence regarding topical long term treatment was available for the two-compound-formulation containing calcipotriene and betamethasone. In a comparative trial in psoriasis vulgaris the two-compound-formulation showed superior tolerability and cost effectiveness compared to monotherapy. In scalp psoriasis the two-compound-gel was superior compared to calcipotriene monotherapy. Standardized and simplified treatment application modes resulted in a better clinical outcome comparing to on-demand therapies. DAILY PRACTICE RECOMMENDATIONS: Patients should be proactively involved in the choice of treatment, formulation and mode of application. Besides long-term treatment with the two-compound-formulation other treatment regimens including calcipotriene monotherapy can also be considered. Due to a favorable risk-benefit ratio in maintenance trials and due to better cost-effectiveness the application of two-compound-products once or twice a week after initial therapy is recommended.

Metastatic cutaneous squamous cell carcinoma arising from a previous area of chronic hypertrophic lichen planus.

Malignant transformation of cutaneous lichen planus is a rare event. We report a 34 year old Caucasian male who presented with an exophytic tumor on the right foreleg. The tumor gradually developed within previous areas of histologically proven hypertrophic lichen planus that had existed for about 10 years. However, the current histological examination of the excised tumor revealed highly differentiated squamous cell carcinoma with a depth of tumor invasion of 10 mm. At that time, neither sentinel lymph node biopsy nor further imaging diagnostics revealed evidence for metastatic spreading. Nevertheless, five months after surgery inguinal lymph node metastases were detected. Initial chemotherapy and inguinal lymph node dissection were unable to stop the spread of the tumor. One year later, parailiacal lymph node metastases were detected by computed tomography. Further cycles of chemotherapy resulted in significant reduction of the parailiacal tumor masses. This report indicates that the long-standing hypertrophic form of lichen planus seems to have a considerable propensity for malignant transformation, even in young patients.