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

RMD Open, vol. 9, pp. e002934

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.

Authors 13

1. Pascal Richette corresponding

   Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Bioscar · Hôpital Lariboisière

   Affiliation as printed

   Rheumatology Department, AP-HP, Lariboisière Hospital, INSERM U1132, Paris, France

   Université Paris Cité, Paris, France

   AP-HP, Lariboisière Hospital, INSERM U1132

   Rheumatology Department

   Université Paris Cité

2. Marijn Vis

   Erasmus MC

   Affiliation as printed

   Rheumatology, Erasmus MC Universitair Medisch Centrum, Rotterdam, The Netherlands

   Erasmus MC Universitair Medisch Centrum

   Rheumatology

3. Sarah Ohrndorf

   Stiftung Charité · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany

   Charité – Universitätsmedizin Berlin

   Department of Rheumatology and Clinical Immunology

4. William L. Tillett

   Royal National Hospital for Rheumatic Diseases · University of Bath

   Affiliation as printed

   Department of Life Sciences, Centre for Therapeutic Innovation, University of Bath, Bath, UK

   Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK

   Department of Life Sciences, Centre for Therapeutic Innovation

   Department of Rheumatology

   Royal National Hospital for Rheumatic Diseases

   University of Bath

5. Julio Ramírez

   Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · Universitat de Barcelona

   Affiliation as printed

   Rheumatology Department, Hospital Universitari Clínic and IDIBAPS, Universidad de Barcelona, Barcelona, Spain

   Rheumatology Department, Hospital Universitari Clínic and IDIBAPS

   Universidad de Barcelona

6. Marlies Neuhold

   Cilag (Switzerland)

   Affiliation as printed

   EMEA Medical Affairs Immunology, Janssen-Cilag, Zug, Switzerland

   EMEA Medical Affairs Immunology

   Janssen-Cilag

7. Michel van Speybroeck

   Janssen (Belgium)

   Affiliation as printed

   Janssen Pharmaceutica, Beerse, Belgium

   Janssen Pharmaceutica

8. Elke Theander

   Cilag (Switzerland)

   Affiliation as printed

   EMEA Medical Affairs Immunology, Janssen-Cilag, Solna, Sweden

   EMEA Medical Affairs Immunology

   Janssen-Cilag

9. Wim Noël Aachen EMEA Medical Affairs Immunology

   Janssen (Netherlands) · Cilag (Switzerland)

   Affiliation as printed

   EMEA Medical Affairs Immunology, Janssen-Cilag BV, Breda, The Netherlands

   EMEA Medical Affairs Immunology

   Janssen-Cilag BV

10. Miriam Zimmermann

    Cilag (Switzerland)

    Affiliation as printed

    EMEA Medical Affairs Immunology, Janssen-Cilag, Zug, Switzerland

    EMEA Medical Affairs Immunology

    Janssen-Cilag

11. May Shawi
    Affiliation as printed

    Medical Affairs, Janssen Global Services LLC, Horsham, Pennsylvania, USA

    Janssen Global Services LLC

    Medical Affairs

12. Alexa P. Kollmeier

    Janssen Research & Development (United States)

    Affiliation as printed

    Research and Development, Immunology, Janssen Research and Development LLC, San Diego, California, USA

    Janssen Research and Development LLC

    Research and Development, Immunology

13. Alen Zabotti

    University of Udine

    Affiliation as printed

    Department of Medical and Biological Sciences, Rheumatology Institute, University of Udine, Udine, Italy

    Department of Medical and Biological Sciences, Rheumatology Institute

    University of Udine