Secukinumab: a new treatment option for psoriatic arthritis

Introduction: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required. Objectives: The interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA. Results: Across two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache. Conclusion: Secukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality

Enthesitis in psoriatic arthritis (Part 3): clinical assessment and management.

Enthesitis is a common clinical feature of PsA, which is characterized by inflammation at the site of insertion of tendons, ligaments and joint capsule fibres into bone. Enthesitis is relatively unique to the spondyloarthritides, setting this group of diseases apart from other rheumatological conditions. The pathophysiological underpinnings of this clinical domain, and the imaging assessment of it, are described in accompanying articles in this supplement. The focus of this article is on the assessment of enthesitis by physical examination, the impact of enthesitis on function and quality of life, the impact of concomitant FM on clinical assessment, and the evidence for therapy of enthesitis garnered in trials of biologic and targeted synthetic DMARDs. Several physical examination measures of enthesitis have been developed and have proved reliable in assessment of enthesitis. Enthesitis has a significant deleterious impact on function and quality of life. The presence of concomitant FM in ≤20% of patients may result in artefactual worsening of assessment of disease severity and hinder achievement of the goal of low disease activity or remission. Several targeted therapies, which, for example, target the TNF, IL-17, IL-23, phosphodiesterase 4 or Janus kinase pathways, have shown significant efficacy in the treatment of enthesitis, resulting in improvement of function and quality of life for patients with PsA

Erratum to: Secukinumab: A New Treatment Option for Psoriatic Arthritis

No abstract available

Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis

Objective. To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). Methods. ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age 18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as 40% improvement from baseline (20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and 40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. Results. In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. Conclusion. Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases

Assessing structural damage progression in psoriatic arthritis and its role as an outcome in research.

Psoriatic arthritis (PsA) is an immune-mediated, clinically heterogeneous disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis of the skin and nails. Persistent articular inflammation in patients with PsA can lead to structural damage, which can result in reduced physical function and quality of life. Structural damage can occur rapidly, and irreversible joint damage may be observed if patients are not treated promptly and appropriately. Therefore, evaluating therapeutic agents for their ability to inhibit structural progression has become increasingly important, with radiographic progression becoming a key efficacy outcome in clinical trials in PsA. Here, we review how structural damage and progression are assessed in clinical trials and the use of radiographic progression as a study outcome. We also discuss possible limitations in the current assessment of radiographic progression as well as areas of research that may improve the assessment of structural damage in clinical trials of PsA

Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG