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Axial spondyloarthritis is a disorder that causes joint pain mainly in the spine and can cause deformation of the spine. Psoriatic arthritis and plaque psoriasis are disorders that cause dry, itchy, and raised skin patches. Psoriatic arthritis also causes swollen, stiff, and painful joints. Etanercept is a treatment used to reduce the symptoms of axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis. The aim of treatment is remission, or low disease activity after 12 weeks. In this study, people received etanercept for up to 52 weeks from their usual doctors in Germany. A total of 305 people with axial spondyloarthritis, 254 people with psoriatic arthritis, and 70 people with plaque psoriasis took part in the study. After 12 weeks of treatment, 19 in 100 people with axial spondyloarthritis were in remission and 39 in 100 people had low disease activity. In addition, 38 in 100 people with psoriatic arthritis were in remission and 50 in 100 people had low disease activity. Finally, 7 in 100 people with plaque psoriasis were in remission and 34 in 100 people had low disease activity. These numbers remained mostly stable until the end of the study. People also reported less pain, fatigue, and depression. Most people were able to use less glucocorticoids. The number and types of unwanted side effects were similar to those seen in other studies of etanercept in people with axial spondyloarthritis, psoriatic arthritis, or plaque psoriasis.

Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis.

Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT.

Psoriatic arthritis (PsA) is a type of arthritis associated with inflammation that occurs in almost one-third of patients with the inflammatory skin condition psoriasis. PsA can vary between individuals, and typically causes joint pain, swelling and stiffness, affecting both physical and social well-being. Over the past decade, several new PsA treatments have become available. However, there is currently a lack of agreement about the best treatment options. As PsA is a chronic (long-term) disease, the duration of time a patient continues taking a prescribed treatment (termed “treatment persistence”) is important. The randomised clinical trials used to determine if a treatment works use strict rules to select patients. Therefore, large studies from everyday practice are needed to better understand the effectiveness and safety of these PsA treatments for a wider range of patients. PsABIOnd is a real-life study that will compare guselkumab (an interleukin-23 inhibitor) and interleukin-17 inhibitors, which are two relatively new types of PsA treatments. The study will provide information about how long patients remain on these treatments and how effectively and safely they work over a 3-year period. PsABIOnd will also explore the impact of PsA on participants’ lives by collecting information about their quality of life, disease activity and treatment satisfaction. In addition, participants also taking part in the eDaily by PsABIOnd substudy will wear a watch-like device and use a smartphone-based app to record measurements including activity, sleep, pain and well-being to give a detailed picture of PsA and its impact on patients’ daily lives.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting, the Collaborative Research Network (CRN) met to present updates on several projects. These included the GRAPPA-Industry biomarker projects, Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Axial Involvement in Psoriatic Arthritis Cohort (AXIS) study, and the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES). The meeting concluded with a discussion on pathways to further academia-industry collaboration.

Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40–60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551).

Introduction: Psoriatic arthritis (PsA) is a chronic, progressive disease that places a significant burden on patients and healthcare systems. The SUSTAIN study collected real-world evidence on long-term effectiveness, impact on quality of life, and safety of ustekinumab treatment for PsA. Methods: SUSTAIN was a prospective, non-interventional study conducted in Germany. Patients with active PsA received ustekinumab for 160 weeks in routine clinical care, with assessments at baseline, week 4, and every 12 weeks thereafter. This analysis focuses on patients who remained in SUSTAIN until week 160. Results: Of 337 patients enrolled, 129 were documented at week 160, of which 123 (95.3%) had received previous PsA medication, including biologics. Decreases from baseline to week 4 were observed for tender joint count (TJC, 8.0 to 5.8) and swollen joint count (SJC, 4.5 to 3.1); these decreases continued to week 28 and were maintained to week 160 (1.0 and 0.4, respectively). Similarly, skin assessments in patients with PsA and psoriasis revealed improvement at week 4, which continued to week 28, with a sustained effect until week 160. Similar patterns of response were observed for patient-assessed pain, sleep quality, and health scores. Improvements in TJC, SJC, Psoriasis Area and Severity Index, and affected body surface area were observed irrespective of the number of prior biologic therapies used. Minimal disease activity was achieved by 36 (31.9%) patients at week 28, and by 38 (33.6%) at week 52. Ustekinumab-related adverse events (AEs) and serious AEs were reported in 61 (47.3%) and 4 (3.1%) patients, respectively. At week 160, 100% of patients assessed ustekinumab tolerability as good or very good. Conclusions: In a real-world setting, patients with active PsA who received ustekinumab until 160 weeks (3 years), including those who received prior biologic therapies, had a rapid onset of effect and sustained response to treatment, with high tolerability. Trial registration: PEI NIS No. 290.

Introduction: The objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks. Methods: In this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP]). Results: Of 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P= 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks. Conclusions: Risankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings. Trial Registration Numbers: NCT02719171 and NCT02986373.

Physicians measure response to treatment of rheumatoid arthritis using a disease activity score (DAS28). People with a DAS28 of less than 2.6 have very few to no symptoms (also called remission). People with a DAS28 of 3.2 or less, called low disease activity, may experience mild symptoms. When people do not respond to treatment after 12 weeks, it is usually recommended to prescribe a different treatment. Researchers do not know how many people who do not respond after 12 weeks would respond if treatment were continued. A total of 824 German people with rheumatoid arthritis who received a drug called etanercept for up to 52 weeks took part in this study. Researchers wanted to know how many people had remission or low disease activity after 12 weeks and 24 weeks of treatment.

The present study was undertaken to evaluate the probability of achieving the Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets of remission or low disease activity (LDA) with apremilast based on disease activity categories and corresponding responses in arthritis and other domains of psoriatic arthritis (PsA) not included in the cDAPSA. Pooled analyses from the Psoriatic Arthritis Long‐term Assessment of Clinical Efficacy studies 1, 2, and 3 were performed. Probability analyses assessing the likelihood of achieving cDAPSAtreatment targets by week 52 were performed using multiple imputation for discontinuations and missing values. Longitudinal analyses were performed in patients grouped by cDAPSAcategory at week 52. Among 494 patients in the probability analyses, 46.9% with moderate disease activity and 24.9% with high disease activity at baseline achieved treatment targets (remission or LDA) by week 52. For patients with moderate disease activity at baseline, small improvements (cDAPSAreductions ≥30%) by week 16 were associated with achieving targets. Patients achieving remission or LDAby week 16 had high probabilities of remaining at treatment targets at week 52. Of 375 patients with cDAPSAcomponents available at week 52, achieving targets with apremilast was associated with continuous disease activity improvements and no or mild arthritis and other PsA manifestations. The probability of achieving treatment targets (remission or LDA) at week 52 was greater for patients with moderate versus high disease activity at baseline. At a mean level, partial improvements by week 16 were associated with achieving treatment targets. Patients receiving apremilast who achieved cDAPSAtargets by week 52 also had no or mild arthritis or other PsA manifestations.

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.

Spondyloarthritis comprises a group of inflammatory diseases, characterised by inflammation within axial joints and/or peripheral arthritis, enthesitis and dactylitis. An increasing number of biologic treatments, including biosimilars, are available for the treatment of spondyloarthritis. Although there are a growing number of randomised controlled trials assessing treatments in spondyloarthritis, there is a paucity of data from head-to-head studies. Comparative data are required so that clinicians and payers have the level of evidence required to inform clinical decision-making and health economic assessments. In the absence of head-to-head studies, statistical methods such as network meta-analyses and matching-adjusted indirect comparisons (MAICs) are used for assessing comparative effectiveness. Network meta-analysis can be used to compare treatments for trials using a common comparator (e.g. placebo); however, for those without a common comparator or where considerable heterogeneity exists between the study populations, a MAIC that controls for differences in study design and baseline patient characteristics may be used. MAICs, unlike network meta-analyses, are of value for longer-term comparisons beyond the placebo-controlled phase of clinical trials, which is important for chronic diseases requiring long-term treatment, like spondyloarthritis. At present, there are a number of limitations that restrict the effectiveness of MAIC, such as the poor availability of individual patient-level data from trials, which results in patient-level data from one trial being compared with published whole-population data from another. Despite these limitations, drug reimbursement agencies are increasingly accepting MAIC as a means of comparative effectiveness and greater methodological guidance is needed. This report highlights a number of challenges that are specific to conducting comparative studies like MAIC in spondyloarthritis, including disease heterogeneity, the paucity of biomarkers and the duration of studies required for radiographic endpoints in this slow-progressing disease.

As in other inflammatory rheumatic diseases, the objective of psoriatic arthritis (PsA) treatment is the achievement of a defined target. Recent recommendations propose aiming for remission or low disease activity; however, a consensual definition of remission is lacking. A state of minimal disease activity (MDA) has been established and is defined by low activity assessed by tender/swollen joint counts, tender entheseal points, Psoriasis Area and Severity Index or body surface area, patient pain and global activity visual analog scale, and functional evaluation by Health Assessment Questionnaire. Since its development, MDA has been used increasingly in studies and clinical trials. In this article, the potential use of MDA as a treatment target in PsA is reviewed. The frequencies of MDA achievement with biologic disease-modifying antirheumatic drugs are summarized based on data from registries, observational studies, and clinical trials. Predictors and the prognostic effect of attaining MDA are also evaluated.

Objective.To evaluate patients with psoriatic arthritis (PsA) receiving etanercept (ETN) monotherapy or ETN plus conventional synthetic disease-modifying antirheumatic drugs (csDMARD) to determine the proportion achieving a clinically meaningful response in arthritis, psoriasis, and quality of life simultaneously.Methods.A prospective, multicenter, 52-week observational study in patients with active PsA evaluated treatment with ETN in clinical practice (ClinicalTrials.gov: NCT00293722). This analysis assessed simultaneous achievement of 3 treatment targets: low disease activity (LDA) based on 28-joint count Disease Activity Score (DAS28); body surface area (BSA) involvement ≤ 3%; and a score > 45 on the Medical Outcomes Study Short Form-12 (SF-12) physical component summary.Results.Of 579 patients, 380 received ETN monotherapy and 199 received combination ETN plus csDMARD. At 52 weeks, data for all 3 disease domains were available for 251 patients receiving monotherapy and 151 receiving combination therapy. In the monotherapy and combination therapy groups, 61 (24.3%) and 37 (24.5%) patients, respectively, achieved all 3 treatment targets simultaneously. A significantly greater proportion of patients receiving monotherapy versus combination therapy achieved SF-12 > 45 (43.0% vs 31.8%; p < 0.05) and DAS28 LDA (72.5% vs 62.3%; p < 0.05). Conversely, BSA ≤ 3% was reached by a significantly greater proportion receiving combination therapy (75.5% vs 56.6%; p < 0.001). However, baseline BSA involvement was higher for the monotherapy group.Conclusion.While nearly half the patients achieved arthritis and psoriasis treatment targets simultaneously and one-fourth reached all 3 treatment targets, combining ETN and csDMARD did not substantially improve clinical response compared with ETN monotherapy in this real-world PsA patient population.

Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations. In this review, the ambitious programme of work to be undertaken by HIPPOCRATES is outlined and common approaches and challenges are identified. It is expected that, when completed, the results will ultimately allow for changes in the approaches to diagnosing, managing and treating PsA allowing for better short-term and long-term outcomes.

To use statistical methods to establish a threshold for individual response in patient‐reported outcomes (PROs) in patients with rheumatoid arthritis. We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (dcrit) for the minimum change associated with a significant individual patient response (beyond normal variation) in the PRO measures of pain (0–10), fatigue (0–10), and function (Funktionsfragebogen Hannover questionnaire; 0–100). We then evaluated PRO responses in patients initiating adalimumab in a noninterventional study (treatment cohort). In the discovery cohort (n = 700), PROs showed excellent long‐term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n = 2,788), 1,483 patients (53.2%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)–dcrit(≥1.8 points) after 12 months of adalimumab treatment; 68.5% of patients with a DAS28‐dcritresponse achieved a significant improvement in pain, whereas approximately 40% achieved significant improvements in fatigue or function. Significant improvements in all 3 PROs occurred in 22.7% of patients; 22.8% did not have any significant PRO responses. In contrast, significant improvements in all 3 PROs occurred in only 4.4% of 1,305 patients who did not achieve a DAS28‐dcritresponse at month 12, and 59.1% did not achieve any significant PRO responses. The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management.

Objective.To examine the influence of concomitant methotrexate (MTX) with adalimumab (ADA) on outcomes in patients with psoriatic arthritis (PsA) using data from an observational study of ADA.Methods.Data from a German noninterventional study of patients with PsA starting treatment with ADA were analyzed retrospectively for effects of concomitant MTX on key outcomes, including Disease Activity Score-28 joints, tender and swollen joint counts, skin assessments, and safety. Patients were categorized into those with symptoms of axial involvement and those with no symptoms of axial involvement as judged by the examining clinician.Results.A total of 1455 patients met the study criteria, 296 with axial involvement (ADA monotherapy = 165; plus MTX = 131) and 1159 with no axial involvement (ADA monotherapy = 658; plus MTX = 501). ADA, alone or combined with MTX, resulted in strong and comparable reductions in disease activity measures in patients with and those without axial disease over 24 months of therapy. In multiple regression analyses, concomitant MTX did not affect joint or skin outcomes in either the group with axial manifestations or the group without axial disease. Neither adverse event rates nor withdrawal rates were significantly influenced by concomitant MTX.Conclusion.ADA is an effective treatment option for patients with PsA with or without axial involvement. Compared with ADA monotherapy, the use of concomitant MTX with ADA does not improve articular or skin outcomes in patients with PsA regardless of axial symptoms. Trial registration: Clinicaltrials.govNCT01111240

Objective.To evaluate the clinical/functional outcomes associated with etanercept (ETN) monotherapy versus combination therapy in psoriatic arthritis (PsA).Methods.Data from patients with PsA who received ETN alone (n = 322) or combined with methotrexate (MTX; n = 152) for 24 weeks in 2 placebo-controlled clinical trials were summarized across studies.Results.Similar proportions of patients in the monotherapy and combination therapy groups achieved the PsA Response Criteria (80% and 83%) and the American College of Rheumatology improvements of 20% (ACR20; both 70%); numerically higher proportions receiving monotherapy achieved ACR50 (55% vs 48%) and ACR70 (35% vs 27%). Little between-group difference was observed in the 28-joint Disease Activity Score with C-reactive protein, the Psoriasis Area and Severity Index, and the Health Assessment Questionnaire–Disability Index improvement.Conclusion.ETN with and without MTX provided similar benefits in active PsA.

Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc.

OBJECTIVE: We aimed to assess the current validity status of the Health Assessment Questionnaire–Disability Index (HAQ-DI) and the 36-item Medical Outcomes Study Short Form Health Survey (SF-36). METHODS: Studies using HAQ-DI and/or SF-36 in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (PAH-SSc) were identified through a systematic literature review and assessed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus group criteria. RESULTS: Both HAQ-DI and SF-36 were considered credible (having face validity) and feasible. Based on expert opinion, neither HAQ-DI nor SF-36 was specific for PAH-SSc since their results may be influenced by other aspects of SSc (judged "unclear" with respect to the content validity criterion). In the overall SSc population, there was significant albeit weak correlation between physical component SF-36 scores and pulmonary artery systolic pressure (PASP) by echocardiography (Kendall tau b = –0.2, p < 0.01). Although HAQ-DI also correlated with PASP by echocardiography, there were no significant correlations in SSc patients with PAH proven by right heart catheterization between changes in HAQ-DI over time and changes in other PAH measures including 6-min walk distance (r = –0.04, p = 0.86), expert global assessment (r = 0.06, p = 0.97), and New York Heart Association functional class (r = 0.38, p = 0.39), indicating lack of construct validity for HAQ-DI in PAH-SSc. No studies enabling assessment of criterion validity or discrimination of HAQ-DI or SF-36 in PAH-SSc could be identified. CONCLUSION: Further validation of HAQ and SF-36 in PAH-SSc is needed. Alternatively, more specific assessments for functional disability or quality of life in PAH-SSc might be required.

Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals.

OBJECTIVE: To assess the validation status of echocardiography with continuous Doppler (echo-Doppler) as an outcome measure in pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc). METHODS: Structured literature review on full-text English articles was performed using the PubMed and Cochrane databases. Assessment of validation of echo-Doppler was based on the OMERACT filter criteria with the domains truth (face, content, construct, and criterion validity), discrimination, and feasibility. RESULTS: Out of 35 studies eligible for analysis, only 5 included well defined PAH-SSc subgroups (World Health Organization criteria). Echo was considered as having face validity based on expert opinion and high number of studies using echo for evaluation of patients with SSc. Echo was considered partially validated with respect to criterion validity based on significant correlations between echo measures and right-heart catheterization in patients with SSc at risk of PAH/PH. However, echo was found to lack specificity (lack of content validity), since measurements of echo pulmonary pressure may be influenced by left-heart disease and interstitial lung disease. Data from general populations of patients with scleroderma indicate that evaluation of pulmonary artery pressure by echo might not be available in all PAH-SSc patients because of technical factors. No studies enabling evaluation of the discriminant capacity over time and treatment of echo in PAH-SSc could be identified. CONCLUSION: Further studies are needed to fully validate echo-Doppler as an outcome measure in PAH-SSc. These studies would include cross-sectional analysis of baseline measures and longitudinal data of placebo and verum groups in randomized controlled trials of patients with PAH-SSc.

There have been steady efforts to develop a combined response index for systemic sclerosis (CRISS). A parallel and equally successful effort has been made by an Expert Panel on Outcome Measures in PAH related to Systemic Sclerosis (EPOSS) to measure effect in treatment of pulmonary arterial hypertension of systemic sclerosis (PAH-SSc). CRISS conducted a Delphi process combined with expert review to identify 11 candidate domains for inclusion in a core set of outcomes for SSc clinical trials: soluble biomarkers, cardiac, digital ulcers, gastrointestinal, global health, health related quality of life (HRQOL) and function, musculoskeletal, pulmonary, Raynaud’s, renal, and skin. Tools within domains were also agreed upon. Concentrating on one aspect of disease, PAH, EPOSS also conducted a Delphi process and judged the following domains as the most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure, cardiac function, exercise testing; severity of dyspnea, discontinuation of treatment; quality of life/activities of daily living; global state; and survival. Possible useful tools within each domain were also agreed on. Patient derived, physician derived, and objective measures of response will be included and combined with the idea that each reflects different aspects of PAH (EPOSS) and overall disease (CRISS) although this assumption may not prove true and can be separated if statistically and clinically valid to do so. In either case, prospective studies will require measurement of all domains, and tools are required and will be developed to define appropriate combined measures of response. CRISS and EPOSS are being developed through the OMERACT process. Through Delphi process and literature review significant progress has been made for both indices, and prospective data are being collected.

Background: Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. Methods: An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This “conflict catalog” was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. Results: Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40–64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59–69% were answered. The most common missing values were CRP, ESR, Schober’s test, data on systemic glucocorticoid therapy, and presence of enthesitis. Conclusion: Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Clinical and genetic registries are an important tool in studying psoriasis and psoriatic arthritis (PsA). They assist in delineating disease features and are crucial in defining phenotype and identifying genetic and other markers of disease expression. At the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of the clinical registries and genetics committees described several ongoing registries, including their construction, protocols, and some results from their analyses. In breakout groups, members discussed data issues, including identification of core datasets, ownership, and how to share data; and ethical issues and possible sources of funding for registries. Proceedings of these meetings are summarized.

ObjectiveOutcome measures for pulmonary arterial hypertension associated with systemic sclerosis PAHSSc are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAHSSc.MethodsSixtynine PAHSSc experts rheumatologists, cardiologists, pulmonologists rated a list of disease domains and measurement tools in an Internetbased 3stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for reratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis.ResultsThe experts judged the following domains and tools as most appropriate for randomized controlled trials in PAHSSc: lung vascularpulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by serious adverse events, quality of lifeactivities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival.ConclusionAmong experts in PAHSSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

Leflunomide (Arava®, Aventis Pharmaceuticals) is an oral pyrimidine synthesis inhibitor with immunomodulatory and anti-inflammatory activity. This agent has demonstrated significant efficacy in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis in randomised, double-blind, placebo-controlled trials. Both the efficacy and safety of leflunomide are maintained with long-term administration in patients with RA. Leflunomide compares favourably with other biological and non-biological agents used to treat RA in the incidence of adverse events and serious adverse events. Economic studies indicate that leflunomide is a cost-effective option in the treatment of RA. New investigations with leflunomide have focused mainly on combination regimens for the treatment of RA and the use of leflunomide in other inflammatory or autoimmune disorders.

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Abstract: The electro-oculogram (EOG) can be recorded by use of skin electrodes positioned near the eye in the horizontal or vertical plane and is dependent on the position of the eye relative to the electrodes and the size of the corneo-retinal potential (CRP). By use of the functional relation between the recorded potential and the eye position - CRP is considered to be constant - the EOG is the eye movement recording method most often used. Changes in CRP dependent on luminance or metabolic influences can be measured, on the other hand, by means of the EOG when eye movements of constant amplitudes are performed. The EOG in this paper is used in the latter sense. The widely used clinical test of rentinal function based on the electro-oculogram firstly described by Arden (Arden index) has been modified to achieve more precise and reliable results by including a gradual dark adaptation procedure and a special data analysis to detect fixation periods. Using modern techniques, the complete procedure has been automated. The efficiency of the procedure and the device is demonstrated in various ways.

The article presents information regarding integrated musicals where the music is blended strongly with the dramatic aspects in a show.

The article focuses on production of compact discs (CDs) filed with music designed for bedtime and relaxation including "Acoustic Dreamland," "The hour of sleep," and "Instrumental Dreamworld."

In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities. The risk allele of p.Asp10Asn (rs33980500) proved to be most significantly associated and to encode a mutant protein with an almost completely disrupted binding property to TRAF6, supporting its impact as a main disease-causing variant and modulator of IL-17 signaling.

The article focuses on the conduct of opera shows and the kind of questions which are asked to the artist after the completion of an act by the media personals. It also mentions some question on topics related to challenges in singing, feelings behind the theater show and information of various shows. According to the author, interviewers should not do conduct unnecessary interviews between the show as it creates for the artists and the audiences

This article discusses the concepts of the so-called mythical outsider element found in musical stage productions. It mentions that the element, also known as the Judas figure, is commonly found in William Shakespeare's comedies, such as "Twelfth Night," "Troilus and Cressida," and "As You Like It". It associates the figure with Jud Fry, the "bad" character in Richard Rogers and Oscar Hammerstein's "Oklahoma!"

The article focuses on the author's view on the mythical story "The Student Prince." He notes the character Trickster who is known in the world mythology in which a certain country knows him as Bugs Bunny. He mentions that in the Viking tales, he is known as Loki, the personification of fire. He cites that the Trickster sometimes trick the Prince and sometimes himself is tricked.

The article offers the author's insights regarding the overlapping definitions of sonata. The author notes that sonata can cause confusions to those who are not music specialists as sonata could mean as an instrumental music from the word sonnade or sonata as a form like Ludwig van Beethoven's piano sonatas. He states that the form of sonata has themes as chosen by composers in a specific key and other themes in related keys called exposition.

The article focuses on the popularity of incidental music for theatrical productions and films. It mentions that the music composed by George Bizet for Daudet's play entitled "L'Arlesienne" has lived on while the play has been forgotten. It adds that the music entitled "The Warsaw Concerto and other Piano Concertos from the Movies" consists of specialized collections of nine piano concertos featured in films such as "Dangerous Moonlight."

The article examines the lives of several music composers in the U.S. who fell victim to their own masterpiece. It infers that composers and artists themselves are not sure of their own work of art that they at often times cause grief upon themselves. An overview of several artists and their work of art is also presented including "Kiss Me Kate," by Cole Porter, "Cavalleria Rusticana," by Pietro Mascagni and "I Pagliacci," by Ruggiero Leoncavallo.