Efficacy and Safety of Intravenous Secukinumab for the Treatment of Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase 3 Study.

Objective: The aim of this study was to evaluate the efficacy and safety of intravenous (IV) secukinumab in patients with active psoriatic arthritis (PsA).

Methods: INVIGORATE-2 (NCT04209205) was a randomized, placebo-controlled, phase 3 trial. Patients with active PsA were randomized 1:1 to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks [q4w]) or placebo.

Efficacy and Safety of Secukinumab in US Patients with Psoriatic Arthritis: A Subgroup Analysis of the Phase 3 FUTURE Studies.

Introduction: The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2-5 studies in patients with psoriatic arthritis (PsA).

Methods: Data were pooled from US patients enrolled in the phase 3 FUTURE 2-5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350).

Quantification of pre-existing radiographic damage and its relationship with joint activity and long-term clinical outcomes with secukinumab therapy in patients with psoriatic arthritis.

Background: Psoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab.

Methods: Pooled data (N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed.

Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial.

Background: Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy.

Methods: In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks.

Long-term Safety of Secukinumab Over Five Years in Patients with Moderate-to-severe Plaque Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis: Update on Integrated Pooled Clinical Trial and Post-marketing Surveillance Data.

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively.

Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis.

Objectives: Identify distinct clusters of psoriatic arthritis (PsA) patients based on their baseline articular, entheseal and cutaneous disease manifestations and explore their clinical and therapeutic value.

Methods: Pooled baseline data in PsA patients (n=1894) treated with secukinumab across four phase 3 studies (FUTURE 2-5) were analysed to determine phenotypes based on clusters of clinical indicators. Finite mixture models methodology was applied to generate clinical clusters and mean longitudinal responses were compared between secukinumab doses (300 vs 150 mg) across identified clusters and clinical indicators through week 52 using machine learning (ML) techniques.

Secukinumab provides sustained improvement in nail psoriasis, signs and symptoms of psoriatic arthritis and low rate of radiographic progression in patients with concomitant nail involvement: 2-year results from the Phase III FUTURE 5 study.

Objectives: To evaluate the impact of secukinumab on nail psoriasis and other psoriatic disease manifestations in patients with psoriatic arthritis (PsA) with concomitant nail psoriasis from the FUTURE 5 study.

Methods: Eligible patients were randomly allocated to receive subcutaneous secukinumab (300 mg load [300 mg], 150 mg load [150 mg], and 150 mg [no load]) or placebo weekly and then every 4 weeks starting Week 4. Key assessments through Week 104 in this post hoc analysis included modified Nail Psoriasis Severity (mNAPSI), Psoriasis Area and Severity Index (PASI 90), resolution of dactylitis and enthesitis, Dermatology Life Quality Index (DLQI) and radiographic progression (assessed by vdH-mTSS).

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.

Sequential knockoffs for continuous and categorical predictors: With application to a large psoriatic arthritis clinical trial pool.

Knockoffs provide a general framework for controlling the false discovery rate when performing variable selection. Much of the Knockoffs literature focuses on theoretical challenges and we recognize a need for bringing some of the current ideas into practice. In this paper we propose a sequential algorithm for generating knockoffs when underlying data consists of both continuous and categorical (factor) variables.

Secukinumab's effect on structural damage progression in psoriatic arthritis: longitudinal mixture modelling of FUTURE-1 and FUTURE-5.

Objectives: Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of treatment effects in subgroups of patients with different rates of structural damage progression.

Methods: We analysed data from two large Phase-3 trials of secukinumab in PsA patients, FUTURE-1 (NCT01392326, n=606) and FUTURE-5 (NCT02404350, n=996), where different posologies ranging from 75 mg to 300 mg were used.

Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

Objectives: Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients.

Methods: The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses.

Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled, phase 3b trial.

Background: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response.

Methods: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis.

Long-term efficacy and safety of secukinumab in patients with psoriatic arthritis: 5-year (end-of-study) results from the phase 3 FUTURE 2 study.

Background: Secukinumab is an interleukin-17A inhibitor used in the treatment of patients with active psoriatic arthritis. In the phase 3 FUTURE 2 trial, secukinumab showed sustained improvement in clinical outcomes over 2 years. Because scarce data exists on the long-term treatment with biological therapies in patients with psoriatic arthritis, we aimed to assess and describe the 5-year (end-of-study) results on the efficacy and safety of secukinumab 300 mg and 150 mg doses, as well as dose escalation, from the FUTURE 2 study.

Secukinumab Efficacy in Psoriatic Arthritis: Machine Learning and Meta-analysis of Four Phase 3 Trials.

Background: Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints.

Methods: Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors.

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.

Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies.

Background: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

Effect of Secukinumab on the Different GRAPPA-OMERACT Core Domains in Psoriatic Arthritis: A Pooled Analysis of 2049 Patients.

Objective: To compare the efficacy of secukinumab with that of placebo across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and Outcome Measures in Rheumatology (GRAPPA-OMERACT) individual psoriatic arthritis (PsA) core domains using pooled data from 4 phase III PsA studies and 1 phase III ankylosing spondylitis (AS) study.

Methods: Data were pooled from 2049 patients with PsA participating in 4 on-label phase III PsA studies (FUTURE 2-5), and the efficacy of each GRAPPA-OMERACT PsA core domain (musculoskeletal disease activity, skin disease activity, pain, patient's global assessment, physical function, health-related quality of life, fatigue, and systemic inflammation) was assessed using multiple measures and definitions specific to each domain. The MEASURE 2 study, a phase III clinical trial in patients with AS, was used to assess improvement in spine symptoms at Week 16.

Secukinumab provides sustained low rates of radiographic progression in psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.

Objective: To evaluate the effect of secukinumab on radiographic progression through 52 weeks in patients with PsA from the FUTURE 5 study.

Methods: Patients with active PsA, stratified by prior anti-TNF use (naïve or inadequate response), were randomized to s.c.

Comparative effectiveness of secukinumab and etanercept in biologic-naïve patients with psoriatic arthritis assessed by matching-adjusted indirect comparison.

Objective: Matching-adjusted indirect comparison (MAIC) can be used to assess the comparative effectiveness of two treatments indirectly using data from randomized placebo-controlled trials. This MAIC assessed the comparative effectiveness of secukinumab (an anti-interleukin-17A) and etanercept (a tumor necrosis factor inhibitor) in a target population of biologic-naïve patients with psoriatic arthritis (PsA).

Methods: Individual patient data pooled from FUTURE 2 (NCT01752634), FUTURE 3 (NCT01989468), and FUTURE 5 (NCT02404350) (secukinumab: 150 mg, n=458 and 300 mg, n=461) were matched to data from the population in the NCT00317499 trial (etanercept 25 mg, n=101) using MAIC methodology, by adjusting for clinical and demographic baseline characteristics.

Efficacy and Safety of Subcutaneous Secukinumab 150 mg with or Without Loading Regimen in Psoriatic Arthritis: Results from the FUTURE 4 Study.

Introduction: To assess the efficacy and safety of the subcutaneous (s.c.) secukinumab 150 mg with loading (150 mg) or without loading (150 mg no-load) regimen through 104 weeks in patients with active psoriatic arthritis (PsA) in the FUTURE 4 (NCT02294227) study.

Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis.

Objective: Secukinumab, a fully human antiinterleukin 17A monoclonal antibody, is efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). This study examined the immunogenicity of secukinumab in patients with PsA and AS exposed to secukinumab for up to 52 weeks.

Methods: Antibody bridging assays were used to assess the immunogenicity of secukinumab in patients with PsA [FUTURE 1-3 studies, and AS (MEASURE 1-4 studies)].

Matching-adjusted indirect comparison: secukinumab versus infliximab in biologic-naive patients with psoriatic arthritis.

To compare secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Individual patient baseline data for secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for secukinumab, for comparison with infliximab. There were no differences in outcomes between secukinumab and infliximab at weeks 6/8 and 14/16.

Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials.

Objectives: Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials.

Methods: Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication.

Secukinumab for psoriatic arthritis: comparative effectiveness versus licensed biologics/apremilast: a network meta-analysis.

Aim: A network meta-analysis using randomized controlled trial data compared psoriatic arthritis (PsA) outcomes (American College of Rheumatology [ACR], Psoriasis Area Severity Index [PASI] and Psoriatic Arthritis Response Criteria [PsARC] response rates) at 12-16 weeks for secukinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, infliximab and ustekinumab.

Patients & Methods: Trials were identified by systematic review. Separate networks were developed for the full-study populations, biologic-naive patients and biologic-experienced patients.

Secukinumab in the treatment of psoriatic arthritis: efficacy and safety results through 3 years from the year 1 extension of the randomised phase III FUTURE 1 trial.

Objective: To assess the long-term (3 year) efficacy and safety of secukinumab in patients with active psoriatic arthritis (PsA) in the extension phase of the FUTURE 1 study (NCT01892436).

Methods: Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab 150 or 75 mg entered a 3-year extension phase. Results are presented for key efficacy and safety endpoints at week 156.