Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.

BACKGROUND: CT-P43 is a candidate ustekinumab biosimilar in clinical development. OBJECTIVES: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. METHODS: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. RESULTS: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. CONCLUSIONS: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

Combined application of information theory on laboratory results with classification and regression tree analysis: analysis of unnecessary biopsy for prostate cancer.

BACKGROUND: The probability of a prostate cancer-positive biopsy result varies with PSA concentration. Thus, we applied information theory on classification and regression tree (CART) analysis for decision making predicting the probability of a biopsy result at various PSA concentrations. METHODS: From 2007 to 2009, prostate biopsies were performed in 664 referred patients in a tertiary hospital. We created 2 CART models based on the information theory: one for moderate uncertainty (PSA concentration: 2.5-10 ng/ml) and the other for high uncertainty (PSA concentration: 10-25 ng/ml). RESULTS: The CART model for moderate uncertainty (n=321) had 3 splits based on PSA density (PSAD), hypoechoic nodules, and age and the other CART for high uncertainty (n=160) had 2 splits based on prostate volume and percent-free PSA. In this validation set, the patients (14.3% and 14.0% for moderate and high uncertainty groups, respectively) could avoid unnecessary biopsies without false-negative results. CONCLUSIONS: Using these CART models based on uncertainty information of PSA, the overall reduction in unnecessary prostate biopsies was 14.0-14.3% and CART models were simplified. Using uncertainty of laboratory results from information theoretic approach can provide additional information for decision analysis such as CART.

[Study on interpretation of quantitative results of prostate-specific antigen using information theory].

BACKGROUND: The prostate-specific antigen (PSA) is considered the most useful among tumor markers currently used. However, its quantitative results are interpreted only qualitatively for the diagnosis of prostate cancer. The recently introduced information theory enables the information of the quantitative results transformed into Shannon's entropy (S) that represents uncertainties and then "1-S" representing diagnostic certainty. METHODS: The 882 urological patients enrolled were categorized into 2 groups: a patient group comprising 233 patients with prostate cancer and a disease control group comprising 649 patients with benign prostate disease. The level of PSA in all the patients was tested and was found to be >or=2 ng/mL. The variables like PSA level and age were modeled on logistic regression analysis to predict the probability of prostate cancer and the diagnostic certainty. RESULTS: The mean (SD) of PSA levels in the patient group and the disease control group were 44.5 ng/mL (37.62 ng/mL) and 5.7 ng/mL (3.70 ng/mL), respectively. The logistic regression model fitted well when the age variable was dichotomized at the age of 55 yr. The diagnostic certainty was lowest at a PSA level of 18.90 ng/mL in the <55-yr age group, and 15.45 ng/mL in the >55-yr age group. CONCLUSIONS: The diagnostic certainty (1-S) of whether to diagnose prostate cancer or not at a certain PSA level could be obtained using the information theory. The methodology used in this study may help interpret the results of other quantitative tests.