Impact of Ixekizumab Treatment on Itch and Psoriasis Area and Severity Index in Patients with Moderate-to-Severe Plaque Psoriasis: An Integrated Analysis of Two Phase III Randomized Studies.

INTRODUCTION: We evaluated baseline itch and its impact on the efficacy of ixekizumab (IXE) in clearing psoriasis and improving quality-of-life measures, and we explored the relationship between itch and psoriatic skin improvement. METHODS: Data were analyzed from two double-blind, randomized, controlled phase III studies (UNCOVER-2/3) comparing etanercept (ETN), IXE, and placebo (PBO) in patients with moderate-to-severe plaque psoriasis. Long-term analysis included UNCOVER-3 data from week 0 to week 156. RESULTS: At week 12, a clinically meaningful improvement in itch [Itch Numeric Rating Scale (NRS) reduction ≥ 4] was seen in 70.0%, 88.6%, and 90.8% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively (all itch severity groups p < 0.001 versus ETN and PBO). Also, 68.9%, 67.1%, and 73.6% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively, showed an improvement of ≥ 90.0% in the Psoriatic Area and Severity Index (PASI) at week 12 as compared to the baseline (PASI 90) (all itch severity groups p < 0.001 versus ETN and PBO). For most patients, itch reduction preceded psoriatic plaque improvement. Sustained effects of IXE on itch and PASI were observed during 3 years of treatment. CONCLUSIONS: Regardless of baseline itch severity, IXE treatment provided a rapid improvement in itch followed by clinically meaningful improvements in psoriasis. FUNDING: Eli Lilly and Company. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01597245 and NCT01646177.

Effectiveness of two formulations of oral olanzapine in patients with schizophrenia or bipolar disorder in a natural setting: results from a 1-year European observational study.

OBJECTIVE: This study aims to assess the proportion of patients with schizophrenia or bipolar disorder who discontinued treatment with one of two oral formulations of olanzapine within 12 months in outpatient settings in Germany, Greece, and France. METHODS: This 1-year, prospective, observational study included patients who had recently initiated treatment with olanzapine-coated tablets (OC) or the orodispersible (OD) formulation. Primary endpoint was olanzapine discontinuation for any reason. Clinical and functional status were also evaluated. RESULTS: Out of 927 enrolled patients, 903 were included in the analyses (612 patients with schizophrenia, 291 with bipolar disorder). Within 12 months, 46 of 903 patients discontinued olanzapine. Most (95%) patients remained on olanzapine for 12 months with similar rates for patients with either diagnosis (94.5% for schizophrenia, 94.9% for bipolar disorder) and for both formulations (93.7% with OC, 95.3% with OD). The only factor significantly associated with time to discontinuation was baseline disease severity. Patients with more severe disease at baseline had a lower discontinuation risk. There were significant improvements in functioning and well-being and non-significant improvements in therapeutic alliance and compliance. CONCLUSIONS: No significant difference was seen between discontinuation rates of the two formulations. Higher baseline severity was associated with a lower discontinuation rate.

Hexadecane and Tween 80 stimulate lipase production in Burkholderia glumae by different mechanisms.

Burkholderia glumae strain PG1 produces a lipase of biotechnological relevance. Lipase production by this strain and its derivative LU8093, which was obtained through classical strain improvement, was investigated under different conditions. When 10% hexadecane was included in the growth medium, lipolytic activity in both strains could be increased approximately 7-fold after 24 h of growth. Hexadecane also stimulated lipase production in a strain containing the lipase gene fused to the tac promoter, indicating that hexadecane did not affect lipase gene expression at the transcriptional level, which was confirmed using lipA-gfp reporter constructs. Instead, hexadecane appeared to enhance lipase secretion, since the amounts of lipase in the culture supernatant increased in the presence of hexadecane, with a concomitant decrease in the cells, even when protein synthesis was inhibited with chloramphenicol. In the presence of olive oil as a carbon source, nonionic detergents, such as Tween 80, increased extracellular lipase activity twofold. Like hexadecane, Tween 80 appeared to stimulate lipase secretion, although in a more disruptive manner, since other, normally nonsecreted proteins were found in the culture supernatant. Additionally, like olive oil, Tween 80 was found to induce lipase gene expression in strain PG1 in medium containing sucrose as a carbon source but not in glucose-containing medium, suggesting that lipase gene expression is prone to catabolite repression. In contrast, lipase production in the lipase-overproducing strain LU8093 was independent of the presence of an inducer and was not inhibited by glucose. In conclusion, hexadecane and Tween 80 enhance lipase production in B. glumae, and they act via different mechanisms.