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.

Development and validation of an instrument to measure the effects of a mistletoe preparation on quality of life of cancer patients: the Life Quality Lectin-53 (LQL-53) Questionnaire.

Mistletoe preparations standardised to the content of mistletoe lectin are supposed to improve quality of life (QoL) in patients with cancer. To obtain a validated and sensitive research instrument, the Life Quality Lectin-53 (LQL-53) Questionnaire was developed in three phases: item generation via interviews with 42 patients, item selection by means of a study with 109 cancer patients, and psychometric testing. The LQL-53 includes 46 items assigned to the subscales 'General well-being', 'Emotional well-being', 'Vitality' 'Hope', 'Locus of control', Social relationships', and 'Physical complaints', plus seven items dealing with possible adverse effects of mistletoe treatment. Psychometric testing was carried out in a study with 112 patients with solid tumours who were treated with a mistletoe preparation standardised to mistletoe lectins for 12 weeks. Internal consistency (Cronbach's alpha) was between 0.72 and 0.94. Test-retest reliability was > or = r of 0.72. Subscales correlated highly with external criteria. Construct validity, as determined by Multitrait Scaling Analysis, resulted in an optimal assignment of items to subscales (scaling success) for four of the subscales. During the course of the therapy, significant improvement in QoL was found in all subscales. In two of the subscales, effect size was high (>0.80), and in five other subscales it varied between 0.53 and 0.78.