Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study

Objectives. To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods. Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT0175263

Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Psoriatic Arthritis: Final 5-year Results from the Phase 3 FUTURE 1 Study.

OBJECTIVE: To report the 5-year efficacy and safety of secukinumab in the treatment of patients with psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326). METHODS: Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab entered a 3-year extension phase. Results are presented for key efficacy endpoints for the secukinumab 150-mg group (n = 236), including patients who escalated from 150 to 300 mg (approved doses) starting at week 156. Safety is reported for all patients (n = 587) who received 1 dose or more of study treatment. RESULTS: Overall, 81.8%% (193 of 236) of patients in the secukinumab 150-mg group completed 5 years of treatment, of which 36.4% (86 of 236) had dose escalation from 150 to 300 mg. Sustained improvements were achieved with secukinumab across all key efficacy endpoints through 5 years. Overall, 71.0%/51.8%/36.3% of patients achieved American College of Rheumatology (ACR) 20/50/70 responses at 5 years. Efficacy improved in patients requiring dose escalation from 150 to 300 mg and was comparable with those who did not require dose escalation. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years for any secukinumab dose were serious infections (1.8), Crohn\u27s disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5). CONCLUSION: Secukinumab provided sustained improvements in the signs and symptoms in the major clinical domains of PsA. Efficacy improved for patients requiring dose escalation from 150 to 300 mg during the study. Secukinumab was well tolerated with no new safety signals

LFA-1 expression in a series of colorectal adenocarcinomas

LFA-1 is an adhesion molecule which belongs to the β2-integrin family. Overexpression of LFA-1 in hepatic natural killer cells has been associated with increased apoptosis of neoplastic cells in colorectal cancer (CRC); moreover, studies in CRC have linked LFA-1 overexpression in neoplastic cells with vascular intrusion through adhesion to endothelial cells, thus implying a possible role in creation of metastases

Nocebo-Prone Behavior Associated with SARS-CoV-2 Vaccine Hesitancy in Healthcare Workers

Among healthcare workers (HCWs), SARS-CoV-2 vaccine hesitancy may be linked to a higher susceptibility to nocebo effects, i.e., adverse events (AEs) experienced after medical treatments due to negative expectations. To investigate this hypothesis a cross-sectional survey was performed with a self-completed questionnaire that included a tool (Q-No) for the identification of nocebo-prone individuals. A total of 1309 HCWs (67.2% women; 43.4% physicians; 28.4% nurses; 11.5% administrative staff; 16.6% other personnel) completed the questionnaires, among whom 237 (18.1%) had declined vaccination. Q-No scores were ≥15 in 325 participants (24.8%) suggesting nocebo-prone behavior. In a multivariate logistic regression model with Q-No score, age, gender, and occupation as independent variables, estimated odds ratios (ORs) of vaccination were 0.43 (i.e., less likely, p < 0.001) in participants with Q-No score ≥ 15 vs. Q-No score < 15, 0.58 in females vs. males (p = 0.013), and 4.7 (i.e., more likely) in physicians vs. other HCWs (p < 0.001), independent of age, which was not significantly associated with OR of vaccination. At least one adverse effect (AE) was reported by 67.5% of vaccinees, mostly local pain and flu-like symptoms. In a multivariate logistic regression model, with Q-No score, age, gender, and occupation as independent variables, estimated ORs of AE reporting were 2.0 in females vs. males (p < 0.001) and 1.47 in physicians vs. other HCWs (p = 0.017) independently of age and Q-No score, which were not significantly associated with OR of AE. These findings suggest that nocebo-prone behavior in HCWs is associated with SARS-CoV-2 vaccination hesitancy indicating a potential benefit of a campaign focused on nocebo-prone people

Secukinumab provides sustained improvement in signs and symptoms and low radiographic progression in patients with psoriatic arthritis: 2-year (end-of-study) results from the FUTURE 5 study.

OBJECTIVE: Secukinumab provided sustained efficacy, low radiographic progression and consistent safety over 52 weeks in patients with psoriatic arthritis (PsA) in the FUTURE 5 study. Here, we report 2-year (end-of-study) results from this study. METHODS: Adults with active PsA were randomised 2:2:2:3 to receive subcutaneous secukinumab 300 mg load (300 mg), 150 mg load (150 mg), 150 mg no load or placebo at baseline; weeks 1, 2, 3 and 4; and every 4 weeks thereafter. Secukinumab could be escalated from 150 mg to 300 mg starting at week 52, if active signs of disease were observed based on physician\u27s assessment. Assessments at week 104 (2 years) included clinical end points and radiographic damage (mean change in van der Heijde-modified total Sharp score (vdH-mTSS)). Safety analysis included all patients who received ≥1 dose of study medication. RESULTS: Of the 996 patients randomised, 783 patients (78.6%) completed 2 years of treatment. Improvement in clinical end points was sustained through 2 years. The vdH-mTSS (mean change (SD)) was 0.10 (1.74; 300 mg), 0.52 (2.66; 150 mg) and 0.41 (2.20; 150 mg no load) at 2 years. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS ≤0.5) at 2 years was 89.5% (300 mg), 82.3% (150 mg) and 81.1% (150 mg no load). CONCLUSION: Secukinumab with and without loading regimen provided sustained clinical efficacy and low radiographic progression through 2 years in patients with PsA. No new safety findings were reported. TRIAL REGISTRATION NUMBER: NCT02404350