Thistedlittle9091

Primary pharmacokinetic results from part1 supported modification of the part2 study design. Results from part2 demonstrated that etrolizumab exposure was equivalent between devices, with geometric mean ratios (GMRs) between AI and PFS-NSD of 102% (90% confidence interval [CI] 94.2-111) for C

, 98.0% (90% CI 89.3-107) for AUC

, and 97.6% (90% CI 88.6-107) for AUC

. Median t

and mean terminal t

were also similar between devices. GMRs and 90% CIs of all primary pharmacokinetic parameters were fully contained within the predefined equivalence limits (80-125%).

This pharmacokinetic study demonstrated that single SC injections of etrolizumab 105mg using an AI or a PFS-NSD resulted in equivalent etrolizumab exposure and similar safety and tolerability in healthy participants. Taken together, these results support the use of an AI for etrolizumab administration.

NCT02996019.

NCT02996019.

Etrolizumab is a novel, dual-action, anti-β7 integrin antibody in development for patients with moderate to severe ulcerative colitis or Crohn's disease. Phase3 studies use a prefilled syringe (PFS) for etrolizumab administration. In parallel, an autoinjector (AI) is being developed to increase delivery options for patients if etrolizumab is approved. Here we describe the overall development strategy and detail the first-in-human study of this AI.

This open-label study of healthy volunteers evaluated the tolerability and usability of the etrolizumab AI under development. The primary endpoint was the proportion of participants with greater than mild pain following injection. Adverse events (AEs) and usage errors were also assessed. Results were reported by injection site (thigh vs abdomen) and needle training (experienced vs naive). Pharmacokinetic (PK) variability between participants was an exploratory endpoint.

Thirty participants completed the study; 97% of them did not experience any pain greater than mild, and 50% did not experience any pain at all. Three usage errors were observed, one of which resulted in delivery of a partial dose of etrolizumab. learn more No patterns of usage errors were observed. Mild injection site reactions (ISRs) were reported; all resolved by the end of the study. Participants injecting into the abdomen reported more ISRs than those injecting into the thigh; needle training did not influence AE incidence or severity.

Results from this first-in-human study demonstrate that single injections of etrolizumab 105mg using an AI were well tolerated in healthy volunteers, with transient, mild pain and minimal usage errors. Results from this study also informed the design of a subsequent PK comparability study evaluating exposure of etrolizumab administered by either the PFS or the AI. Overall, the availability of an AI may provide an attractive option for patients desiring a convenient, easy-to-use delivery mechanism for etrolizumab.

NCT02629744.

NCT02629744.

Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) is a promising investigational treatment for metastatic castration-resistant prostate cancer (mCRPC). This review describes the available data with PSMA TRT.

Conjugates used for PSMA TRT include antibodies or small molecules PSMA-radiolabeled with beta (most commonly 177Lu) or alpha emitters (commonly 225Ac). 177Lu-J591 demonstrated accurate targeting of known metastatic sites, based on post-treatment scintigraphy, in study populations that were not selected for PSMA expression, with evidence of dose-response and dose-limiting myelosuppression. Early phase studies of 177Lu-PSMA-617 have demonstrated favorable adverse event profiles and signs of clinical activity as evidenced by PSA responses and other short-term outcomes. A phase II randomized study of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans. Pudy of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans. PSMA TRT is emerging as a promising investigational therapy for mCRPC. The first randomized data with 177Lu-PSMA-617 (phase 2) have been presented, and the first phase 3 trial has completed accrual with radiographic progression-free and overall survival as dual primary endpoints. Multiple additional phase 3 trials of PSMA-TRT are starting and studies investigating optimal patient selection and combination therapy continue.

Personal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease.

To explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab.

Treatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥6 months and preferably a Psoriasis Area and Severity Index (PASI) <5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (<50 vs. ≥50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy.

Sixty-five patients were included. 'To be free of itching', 'to be healed of all skin defects' and 'to have confidence in the therapy' were rated quite/very important in 78.5% of the patients, followed by 'to have no fear the disease will progress' (75.4%) and 'to get better skin quickly' (75.4%). Goals related to the subscale 'confidence in healing' were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to 'feel less depressed' and 'be comfortable showing yourself more in public'.

Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level.

Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level.