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  1. Article ; Online: Identification of PsA phenotypes with machine learning analytics using data from two phase III clinical trials of guselkumab in a bio-naïve population of patients with PsA

    Julio Ramírez / Pascal Richette / Alen Zabotti / Sarah Ohrndorf / Elke Theander / Marijn Vis / William Tillett / May Shawi / Wim Noël / Marlies Neuhold / Michel van Speybroeck / Miriam Zimmermann / Alexa Kollmeier

    RMD Open, Vol 9, Iss

    2023  Volume 1

    Abstract: Objectives Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine ... ...

    Abstract Objectives Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.Methods Pooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.Results Eight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.Conclusions Unsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Construct validity and responsiveness of feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis

    Ilja Tchetverikov / Marijn Vis / William Tillett / Maikel van Oosterhout / Faouzia Fodili / Fazira R. Kasiem / Marc R. Kok / Jolanda J. Luime / Lindy-Anne Korswagen / Natasja H.A.M. Denissen / Yvonne P.M. Goekoop-Ruiterman / Johanna M.W. Hazes

    RMD Open, Vol 9, Iss

    2023  Volume 4

    Abstract: Objective There is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue Scale (3VAS) and 4-item Visual Analogue Scale (4VAS) ... ...

    Abstract Objective There is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue Scale (3VAS) and 4-item Visual Analogue Scale (4VAS) were developed. This study aimed to test construct validity and responsiveness of the 3VAS and 4VAS in a population of patients with newly diagnosed PsA receiving usual care.Methods Components of the 3VAS (physician global, patient global, patient skin) and 4VAS (physician global, patient pain, patient joint, patient skin) were scored on 0–10 VAS scales. Agreement of low disease activity (LDA) state between 3VAS/4VAS and other composite measures was tested using Venn diagrams. Construct validity and responsiveness (3-month interval) were assessed using Spearman correlation coefficients and standardised response means (SRM) with effect sizes (ES), respectively, following hypothesis generation. Both 3VAS/4VAS were also compared with several patient-reported outcome measures.Results Data from 629 patients were used. Both 3VAS (ES=0.48, SRM 0.52) and 4VAS (ES=0.48, SRM=0.50) showed responsiveness similar to Disease Activity in PSoriatic Arthritis (DAPSA) and Disease Activity Score-28 (DAS28). Both measures had a strong correlation with DAPSA (r=0.80–0.87), Psoriatic Arthritis Disease Activity Score (PASDAS) (r=0.89) and Routine Assessment of Patient Index Data 3 (RAPID3) (r=0.84–0.92). 3VAS and 4VAS had the highest agreement with PASDAS in categorising patients to LDA at 12 months.Conclusion This is the first study assessing the performance of the 3VAS and 4VAS in an observational cohort of patients with early PsA. Both measures have promising performance characteristics, showing strong correlations and good discrimination with existing composite measures. The 4VAS may be the preferred version with better face validity.
    Keywords Medicine ; R
    Subject code 616 ; 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Treating to target in psoriatic arthritis

    Ines Rombach / William Tillett / Deepak Jadon / Laura Tucker / Marion Watson / Anne Francis / Yvonne Sinomati / Lucy Eldridge / Melina Dritsaki / Susan J. Dutton / Hussein Al-Mossawi / Nicola Gullick / Ben Thompson / Laura C. Coates

    Trials, Vol 22, Iss 1, Pp 1-

    assessing real-world outcomes and optimising therapeutic strategy for adults with psoriatic arthritis—study protocol for the MONITOR-PsA study, a trials within cohorts study design

    2021  Volume 14

    Abstract: Abstract Background The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of ‘step up’ therapy ( ... ...

    Abstract Abstract Background The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of ‘step up’ therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA. Methods The Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease. Discussion This study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes. Trial registration ClinicalTrials.gov NCT03531073 . Retrospectively registered on 21 May 2018.
    Keywords Psoriatic arthritis ; Treat-to-target ; TWiCs ; Trials within cohorts ; Cohort multiple RCT or cmRCT ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Classification and Outcome Measures for Psoriatic Arthritis

    Ying Ying Leung / Alexis Ogdie / Ana-Maria Orbai / William Tillett / Laura C. Coates / Vibeke Strand / Philip Mease / Dafna D. Gladman

    Frontiers in Medicine, Vol

    2018  Volume 5

    Abstract: Psoriatic arthritis (PsA) is an inflammatory arthritis with multiple manifestations: peripheral/axial arthritis, enthesitis, dactylitis, psoriasis, and nail involvement. From having an agreed upon classification criteria in 2006, the assessment of PsA ... ...

    Abstract Psoriatic arthritis (PsA) is an inflammatory arthritis with multiple manifestations: peripheral/axial arthritis, enthesitis, dactylitis, psoriasis, and nail involvement. From having an agreed upon classification criteria in 2006, the assessment of PsA has advanced from uncertainties to development and validation of numerous specific outcome measures. The Group for Research and Assessment of Psoriasis and Psoriatic arthritis (GRAPPA) has spearheaded the development of a core domain set and is now working on a core outcome measurement set to standardize outcome measures for PsA, that will provide guidance for use of instruments in randomized controlled trials (RCTs) and longitudinal observational studies (LOS). This article summarizes and updates these work processes to improve assessment of this multisystem complex rheumatologic disease.
    Keywords psoriatic arthritis ; outcome measures ; core domains ; core instruments ; classification criteria ; Medicine (General) ; R5-920
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The ethics of ‘Trials within Cohorts’ (TwiCs)

    Clare Relton / Maarten Burbach / Clive Collett / James Flory / Sophie Gerlich / Soren Holm / Amanda Hunn / Scott Y. Kim / Linda Kwakkenbos / Anne May / Jon Nicholl / Danny Young-Afat / Shaun Treweek / Rudolf Uher / Tjeerd van Staa / Joanne van der Velden / Helena Verkooijen / Andrew Vickers / Sophie Welch /
    Merrick Zwarenstein / Scott Kim / Zachary Goodman / Søren Holm / Anne M. May / Danny A. Young-Afat / Johannes P. Burbach / Carla H. van Gils / Rieke van der Graaf / Helena M. Verkooijen / Laura C. Coates / William Tillett / David Torgerson / Neil McHugh / Peter Taylor / Lesley Brown / Anne Heaven / John Young / Andrew Clegg / Kate Chatfield / Roxanne Gal / Evelyn M. Monninkhof / Danny A. Young Afat / Rolf H. H. Groenwold

    Trials, Vol 18, Iss S2, Pp 1-

    2nd international symposium

    2017  Volume 10

    Keywords Medicine (General) ; R5-920
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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