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      Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3)

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          Abstract

          Objective

          To evaluate apremilast treatment in patients with active psoriatic arthritis, including current skin involvement, despite prior therapy with conventional disease-modifying antirheumatic drugs and/or biologic agents.

          Methods

          Patients (N=505) were randomised (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients not achieving 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomised to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.

          Results

          At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%; p=0.0295 and p<0.0001, respectively), and mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (−0.20) versus placebo (−0.07; p=0.0073). In patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%; p=0.0098) at week 16. At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment. Most adverse events were mild to moderate in severity; the most common were diarrhoea, nausea, headache and upper respiratory tract infection.

          Conclusions

          Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks. Apremilast was generally well tolerated and demonstrated an acceptable safety profile.

          Trial registration number

          NCT01212770.

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          Most cited references18

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          Psoriatic arthritis: epidemiology, clinical features, course, and outcome.

          Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.
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            American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis.

            Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. We present a definition of improvement which we hope will be used widely in RA trials.
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              The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation.

              Over the last 2 decades, assessment of patient health status has undergone a dramatic paradigm shift, evolving from a predominant reliance on biochemical and physical measurements to an emphasis upon health outcomes based on the patient's personal appreciation of their illness. The Health Assessment Questionnaire (HAQ), published in 1980, was among the first instruments based on patient centered dimensions. The HAQ was designed to represent a model of patient oriented outcome assessment and has played a major role in diverse areas such as prediction of successful aging, inversion of the therapeutic pyramid in rheumatoid arthritis (RA), quantification of nonsteroidal antiinflammatory drug gastropathy, development of risk factor models for osteoarthrosis, and examination of mortality risks in RA. The HAQ has established itself as a valuable, effective, and sensitive tool for measurement of health status. It has increased the credibility and use of validated self-report measurement techniques as a quantifiable set of hard data endpoints and has contributed to a new appreciation of outcome assessment. We review the development, content, and dissemination of the HAQ and provide reference sources for its uses, translations, and validations. We discuss contemporary issues regarding outcome assessment instruments relative to the HAQ's identity and utility. These include: (1) the issue of labeling instruments as generic versus disease-specific; (2) floor and ceiling effects in scales such as "disability"; (3) distances between values on scales; and (4) the continuing introduction of new measurement instruments and their potential effects.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann. Rheum. Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                June 2016
                20 January 2016
                : 75
                : 6
                : 1065-1073
                Affiliations
                [1 ]NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton , Southampton, UK
                [2 ]INIBIC-Hospital Universitario A Coruña , Galicia, Spain
                [3 ]Bakersfield Dermatology , Bakersfield, California, USA
                [4 ]University of Massachusetts Medical School , Worcester, Massachusetts, USA
                [5 ]Reumatika Centrum Reumatologi , Warszawa, Poland
                [6 ]West Tennessee Research Institute , Jackson, Tennessee, USA
                [7 ]Celgene Corporation , Summit, New Jersey, USA
                [8 ]Combined Rheumatology Practice, University of New South Wales , Kogarah, New South Wales, Australia
                Author notes

                Handling editor Tore K Kvien

                [Correspondence to ] Dr Christopher J Edwards, University Hospital Southampton NHS Foundation Trust, Mailpoint 218, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; cedwards@ 123456soton.ac.uk .
                Article
                annrheumdis-2015-207963
                10.1136/annrheumdis-2015-207963
                4893110
                26792812
                8d9d3bb9-9dec-4b28-82af-28055526bd5f
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 21 May 2015
                : 30 November 2015
                : 12 December 2015
                Categories
                1506
                Clinical and Epidemiological Research
                Extended report
                Custom metadata
                unlocked

                Immunology
                psoriatic arthritis,ankylosing spondylitis,treatment
                Immunology
                psoriatic arthritis, ankylosing spondylitis, treatment

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