The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)
Blackpool Victoria Hospital1, University of Leeds2, University College Dublin3, Radboud University Nijmegen4, University of Toronto5, University of Utah6, Royal United Hospital7, University of Washington8, Stanford University9, Federal University of Paraná10, Federal University of Rio de Janeiro11, LSU Health Sciences Center Shreveport12, Johns Hopkins University13, University of Buenos Aires14, Seoul National University15, University of Molise16, University of Cagliari17, University of Queensland18, Federal University of Uberlandia19, University of California, Davis20, Barking, Havering and Redbridge University Hospitals NHS Trust21, University of Naples Federico II22, Hospital Italiano de Buenos Aires23, University of Amsterdam24, Military Hospital25, Katholieke Universiteit Leuven26
TL;DR: Two new composite measures to assess disease activity in PsA have been developed by multiple linear regression and empirically, utilising physician-defined cut-offs for disease activity, and area under the receiver operating curves (AUC) were generally smaller.
Abstract: Objective To develop new composite disease activity indices for psoriatic arthritis (PsA). Methods Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). Results 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index >10) both nonparametric and AUC curve statistics were nonsignificant for all measures. Conclusions Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.
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University of Paris1, Medical University of Vienna2, Leiden University3, Paris Descartes University4, University of Leeds5, Ruhr University Bochum6, Charité7, University College Dublin8, Halmstad University9, Katholieke Universiteit Leuven10, University of Münster11, University of Glasgow12, Charles University in Prague13, University of Erlangen-Nuremberg14, Ghent University Hospital15
TL;DR: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.
Abstract: Background Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. Methods A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. Results The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. Conclusions These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.
802 citations
Ruhr University Bochum1, Paris Descartes University2, University of Toronto3, University of California, San Diego4, University of Washington5, Charité6, Medical University of Vienna7, VU University Amsterdam8, Ghent University Hospital9, University of Oxford10, University of California, San Francisco11, University of Leeds12, University Health Network13, University of Glasgow14, University College London15, University of Pennsylvania16, University of Rochester Medical Center17, Erasmus University Rotterdam18, Katholieke Universiteit Leuven19, Leiden University Medical Center20
TL;DR: There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA.
Abstract: Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.
461 citations
Medical University of Vienna1, Chapel Allerton Hospital2, University of California3, University of Amsterdam4, University of Münster5, University of Washington6, University of Texas Health Science Center at Houston7, University of Rochester Medical Center8, Charité9, National Autonomous University of Mexico10, Sofia University11, Oregon Health & Science University12, Ghent University Hospital13, Pierre-and-Marie-Curie University14, Chung Shan Medical University15, Leiden University Medical Center16
TL;DR: The task force defined the treatment target for SpA as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research.
Abstract: 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 patient9s 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.
419 citations
TL;DR: Tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported.
372 citations
TL;DR: The DAPSA constitutes a disease-specific, validated and feasible tool for PsA assessment and provides criteria for disease activity states and treatment response, based on an international expert survey.
Abstract: Background The Disease Activity Index for Psoriatic Arthritis (DAPSA) is a valid and discriminative tool. Definitions of disease activity states and therapeutic response are still missing. We derived such criteria for the DAPSA. Methods We retrieved 30 patient profiles from an observational database including joint counts, patient pain and global activity ratings and C-reactive protein (CRP) and carried out a survey among experts to classify patients into remission (REM), low (LDA), moderate (MDA) or high (HDA) disease activity. Based on the distributions of DAPSA in each of these expert-assigned states we defined the cutpoints between groups. We performed similar analyses evaluating a clinical score (cDAPSA), omitting CRP. To define minor, moderate and major treatment response, we used Cohen9s Kappa statistics and analysed agreement of DAPSA percentage change with ACR20/50/70-response in three randomised controlled trials. Results Our survey yielded a response rate of 75% (n=33). Mean DAPSA differed significantly between patients classified as REM, LDA, MDA or HDA (p 4 and ≤14 for LDA, >14 and ≤28 for MDA and >28 for HDA. We observed best agreement with ACR20/50/70-response at DAPSA changes of 50/75/85%, reflecting minor, moderate and major improvement. Conclusions The DAPSA constitutes a disease-specific, validated and feasible tool for PsA assessment. In this study, we provide criteria for disease activity states and treatment response. They are based on an international expert survey, and show good performance in clinical trials and observational data.
306 citations
References
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TL;DR: A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis, and these techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.
Abstract: A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis. The paradigm represents outcome by five separate dimensions: death, discomfort, disability, drug (therapeutic) toxicity, and dollar cost. Each dimension represents an outcome directly related to patient welfare. Quantitation of these outcome dimensions may be performed at interview or by patient questionnaire. With standardized, validated questions, similar scores are achieved by both methods. The questionnaire technique is preferred since it is inexpensive and does not require interobserver validation. These techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.
4,253 citations
TL;DR: Ro 10--9359 proved to be an extremely potent antipsoriatic drug and a more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment.
Abstract: Ro 10–9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were ad
2,510 citations
TL;DR: EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA and the World Health Organization and International League Against Rheumatism criteria.
Abstract: Objective. To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WHO)/International League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA).
Methods. EULAR response criteria were developed combining change from baseline and level of disease activity attained during followup. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity.
Results. EULAR response criteria had good construct, criterion, and discriminant validity. ACR and WHO/ILAR criteria showed only good criterion validity.
Conclusion. EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA.
1,529 citations
TL;DR: Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease.
1,381 citations
Journal Article•
TL;DR: Five clinical measurements provide a composite index (BASMI) and define disease status in AS, which is quick, reproducible and sensitive to change across the disease spectrum.
Abstract: OBJECTIVE To determine the most appropriate clinical measurements for the assessment of ankylosing spondylitis (AS) to develop the new metrology index. METHODS One hundred and ninety-three individuals with AS were studied. The patients reflected the entire spectrum of cases of AS. Metrology was performed on 327 occasions. First the metrology (20 measurements) of 43 patients was analyzed. From this, 5 simple clinical measurements were defined which most accurately reflect axial status: cervical rotation, tragus to wall distance, lateral flexion, modified Schober's, and intermalleolar distance. These measurements were assessed for reliability, speed and both inter and intraobserver variability in another 40 patients. RESULTS Analysis of the first group of 43 patients and a subsequent group of 54 patients, using the 5 measurements that constitute this new Bath AS Metrology Index (BASMI), demonstrated that they accurately and reliably mirror the 20 clinical measurements assessed previously (r = 0.92, p < 0.001). In a new group of 40 patients the measurements were demonstrated to be accurate and reproducible for both intraobserver variability (r = 0.99, p < 0.001) and interobserver variability (r = 0.97, p < 0.001). In a further 56 patients, admitted for inpatient therapy, an improvement in the BASMI from 3.34 (SD 2.71) to 2.16 (SD 2.42) was noted over a period of 3 weeks (regardless of disease severity) which indicates a sensitivity to change (chi 2 = 6.55, p < 0.01). The mean improvement over baseline was about 30%. CONCLUSION Five clinical measurements provide a composite index (BASMI) and define disease status in AS. The BASMI is quick (7 min), reproducible and sensitive to change across the disease spectrum.
940 citations