Psoriasis Area and Severity Index response in moderate-severe psoriatic patients switched to adalimumab: results from the OPPSA study

Background: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. Objective: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. Methods: In this multicentre study, psoriasis patients (N = 262) treated with an anti-TNF-alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. Results: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. Conclusion: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF-alpha or IL-12/23 inhibitor

Interregional migration of human creative capital:The case of "Bohemian graduates"

The human capital endowment has long been perceived to be of paramount importance to regional growth and development. In recent years, there also has been a widely held belief that creativity, going hand in hand with innovation and knowledge creation, readily translates into regional competitiveness. Attracting quality human capital and cultivating creative industry/class have been given an unprecedented level of significance in regional policies. As a result of this, understanding the factors determining the migration behaviour of graduates – and especially graduates in creative disciplines – has clear implications for policy makers. In addressing these issues and advancing our understanding of the relationship between creativity and mobility in human capital, this study provides the first empirical analysis of the role played by graduates' subject background (i.e. creative vs. non-creative subjects) in influencing their migration choice in the UK. Our data employed in this paper primarily draw on the Destinations of Lea-vers from Higher Education Survey (DLHE) 2006/2007, collected by the UK's Higher Education Statistic Agency. Graduates are classified into five migration categories based on their migration choices from domicile to university and then onto workplace. Our results show that graduates from disciplines such as business/management and more importantly engineering/technology are more migratory and more likely to be repeat migrants and land higher paid jobs, while graduates from creative arts, education or law are less mobile and, on average, earn less

Myths and lessons of liberal intervention: The British campaign for the abolition of the Atlantic slave trade to Brazil

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 Martinus NijhoffThis article takes issue with recent references to the British nineteenth century campaign for the abolition of the trans-Atlantic slave trade to Brazil that serve to bolster interventionist or imperialist agendas. In particular, such accounts reproduce two and a half myths about the campaign: that it can serve as a model for the present age; that the success of the campaign can be explained through the actions of the intervening party alone (with a corresponding neglect of those of the ‘target’ state); and the half-myth that the campaign’s success was due to military action (at the expense of institutional (legal) and normative factors and the capacity of the target state). I argue instead that this case – and interventions more generally – would benefit from an analysis that considers the role of force in relation to a series of residual institutional and cultural constraints within the liberal state and to political conditions in the target state. In light of the complexities and contingencies that these factors present the underlying lesson is that military force should be used sparingly, if at all

Impact of Symptoms on Daily Life in People at Risk of Rheumatoid Arthritis

Objectives: To explore the impact on daily life of symptoms experienced by those with systemic autoimmunity associated with rheumatoid arthritis (RA). Methods: Fifteen people took part in focus groups to explore the impact of symptoms on daily life. Results: Core themes included: 1) physical impact of limited hand function and mobility; 2) psychological distress experienced included a fear of symptoms progressing into RA, uncertainty about the future, feelings of despair, shame and frustration. Conclusion: People with arthralgia at risk of developing RA experienced considerable physical and psychological impact of symptoms. Greater consideration should be given to the needs of people at risk of developing RA

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set : translation and cross-cultural adaptation into 15 languages

Introduction: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. Discussion: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures

Cost-effectiveness modelling of biological treatment sequences in moderate to severe rheumatoid arthritis in France

Objectives. Modern treatment of RA includes the use of biologics. Their cost is high and comparison between different treatment strategies is needed. Method. Direct medical costs of RA in France were evaluated based on expert opinion. Then, simulation-decision analytical models were developed to assess four biologic treatment sequences over 2 years in patients failing to respond to at least one anti-TNF agent. Effectiveness was expressed in theoretical expected number of days (TEND) in remission or low disease activity [low disease activity score (LDAS)] based on DAS-28 scores. Results. Direct medical costs of RA in France (excluding the cost of biologics) were estimated at €905 (s.d. 263) for 6 months and €696 (s.d. 240) for each subsequent 6 months (P < 0.001) for patients achieving LDAS and €1215 for 6 months (s.d. 405) for patients not achieving LDAS. Based on LDAS criteria, using abatacept after an inadequate response to the first anti-TNF agent (etanercept) appeared significantly (P < 0.01) more efficacious over a 2-year period (102 TEND) compared with using rituximab at a 6-month re-treatment interval (82 TEND). Mean cost-effectiveness ratios showed significantly lower costs (P < 0.01) per TEND with abatacept as second biologic agent (€278) compared with rituximab (€303). After an inadequate response to two anti-TNF agents, using abatacept also appeared significantly more efficacious than an anti-TNF agent (P < 0.01). All comparisons were confirmed when using remission criteria instead of LDAS. Conclusion. Advanced simulation models based on clinical evidence and medical practice appear to be a promising approach for comparing cost-effectiveness of biologic strategies in R

Clinical practice guidelines for the foot and ankle in rheumatoid arthritis: a critical appraisal

Background: Clinical practice guidelines are recommendations systematically developed to assist clinical decision-making and inform healthcare. In current rheumatoid arthritis (RA) guidelines, management of the foot and ankle is under-represented and the quality of recommendation is uncertain. This study aimed to identify and critically appraise clinical practice guidelines for foot and ankle management in RA. Methods: Guidelines were identified electronically and through hand searching. Search terms 'rheumatoid arthritis', 'clinical practice guidelines' and related synonyms were used. Critical appraisal and quality rating were conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: Twenty-four guidelines were included. Five guidelines were high quality and recommended for use. Five high quality and seven low quality guidelines were recommended for use with modifications. Seven guidelines were low quality and not recommended for use. Five early and twelve established RA guidelines were recommended for use. Only two guidelines were foot and ankle specific. Five recommendation domains were identified in both early and established RA guidelines. These were multidisciplinary team care, foot healthcare access, foot health assessment/review, orthoses/insoles/splints, and therapeutic footwear. Established RA guidelines also had an 'other foot care treatments' domain. Conclusions: Foot and ankle management for RA features in many clinical practice guidelines recommended for use. Unfortunately, supporting evidence in the guidelines is low quality. Agreement levels are predominantly 'expert opinion' or 'good clinical practice'. More research investigating foot and ankle management for RA is needed prior to inclusion in clinical practice guidelines

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force

Background: Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective: To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods: Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results: Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions: The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA

Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis

Objectives: To evaluate the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis (RA) and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs. Methods: In this phase III study, patients were randomised 1:1:1 to placebo (N=228), baricitinib 2 mg once daily (QD, N=229) or baricitinib 4 mg QD (N=227). PROs included the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, measures from patient electronic daily diaries (duration and severity of morning joint stiffness (MJS), Worst Tiredness, Worst Joint Pain), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36, EuroQol 5-D index scores and visual analogue scales (VAS) and the Work Productivity and Activity Impairment Questionnaire-RA. The primary time point for the study was week 12. Treatment comparisons were assessed with logistic regression for categorical measures and analysis of covariance for continuous variables. Results: Statistically significant improvements were observed for both baricitinib groups versus placebo in HAQ-DI, PtGA, pain, daily diary measures, EuroQoL index scores and SF-36 physical component score at week 12 and for those measures when assessed at week 24. Baricitinib 2 mg and baricitinib 4 mg were statistically significantly improved versus placebo for the EuroQoL VAS and FACIT-F, respectively, at week 24. Conclusions: Baricitinib 2 or 4 mg provided significant improvement versus placebo in PROs across different domains of RA, including physical function, MJS, fatigue, pain and quality of life