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

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

Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

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

The Power Spectrum of Mass Fluctuations Measured from the Lyman-alpha Forest at Redshift z=2.5

We measure the linear power spectrum of mass density fluctuations at redshift z=2.5 from the \lya forest absorption in a sample of 19 QSO spectra, using the method introduced by Croft et al. (1998). The P(k) measurement covers the range 2\pi/k ~ 450-2350 km/s (2-12 comoving \hmpc for \Omega=1). We examine a number of possible sources of systematic error and find none that are significant on these scales. In particular, we show that spatial variations in the UV background caused by the discreteness of the source population should have negligible effect on our P(k) measurement. We obtain consistent results from the high and low redshift halves of the data set and from an entirely independent sample of nine QSO spectra with mean redshift z=2.1. A power law fit to our measured P(k) yields a logarithmic slope n=-2.25 +/- 0.18 and an amplitude \Delta^2(k_p) = 0.57^{+0.26}_{-0.18}, where $\Delta^2$ is the contribution to the density variance from a unit interval of lnk and k_p=0.008 (km/s)^{-1}. Direct comparison of our mass P(k) to the measured clustering of Lyman Break Galaxies shows that they are a highly biased population, with a bias factor b~2-5. The slope of the linear P(k), never previously measured on these scales, is close to that predicted by models based on inflation and Cold Dark Matter (CDM). The P(k) amplitude is consistent with some scale-invariant, COBE-normalized CDM models (e.g., an open model with \Omega_0=0.4) and inconsistent with others (e.g., \Omega=1). Even with limited dynamic range and substantial statistical uncertainty, a measurement of P(k) that has no unknown ``bias factors'' offers many opportunities for testing theories of structure formation and constraining cosmological parameters. (Shortened)Comment: Submitted to ApJ, 27 emulateapj pages w/ 19 postscript fig

Fatigue in fibromyalgia: a conceptual model informed by patient interviews

Abstract Background Fatigue is increasingly recognized as an important symptom in fibromyalgia (FM). Unknown however is how fatigue is experienced by individuals in the context of FM. We conducted qualitative research in order to better understand aspects of fatigue that might be unique to FM as well as the impact it has on patients' lives. The data obtained informed the development of a conceptual model of fatigue in FM. Methods Open-ended interviews were conducted with 40 individuals with FM (US [n = 20], Germany [n = 10] and France [n = 10]). Transcripts were analyzed using qualitative methods based upon grounded theory to identify key themes and concepts. Results Participants were mostly female (70%) with a mean age of 48.7 years (range: 25-79). Thirty-one individuals (i.e., 77.5%) spontaneously described experiencing tiredness/lack of energy/fatigue due to FM. Participants discussed FM fatigue as being more severe, constant/persistent and unpredictable than normal tiredness. The conceptual model depicts the key elements of fatigue in FM from a patient perspective. This includes: an overwhelming feeling of tiredness (n = 17, 42.5%), not relieved by resting/sleeping (n = 15, 37.5%), not proportional to effort exerted (n = 25, 62.5%), associated with a feeling of weakness/heaviness (n = 20, 50%), interferes with motivation (n = 22, 55%), interferes with desired activities (n = 27, 67.5%), prolongs tasks (n = 15, 37.5%), and makes it difficult to concentrate (n = 21, 52.5%), think clearly (n = 12, 30%) or remember things (n = 9, 22.5%). Conclusion The majority of individuals with FM who participated in this study experience fatigue and describe it as more severe than normal tiredness.http://deepblue.lib.umich.edu/bitstream/2027.42/112483/1/12891_2010_Article_962.pd