Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis

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Pournara, Effie
Kormaksson, Matthias
Nash, Peter
Ritchlin, Christopher T
Kirkham, Bruce W
Ligozio, Gregory
Pricop, Luminita
Ogdie, Alexis
Coates, Laura C
Schett, Georg
McInnes, Iain B
Griffith University Author(s)
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2021
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Abstract

OBJECTIVES: Identify distinct clusters of psoriatic arthritis (PsA) patients based on their baseline articular, entheseal and cutaneous disease manifestations and explore their clinical and therapeutic value. METHODS: Pooled baseline data in PsA patients (n=1894) treated with secukinumab across four phase 3 studies (FUTURE 2-5) were analysed to determine phenotypes based on clusters of clinical indicators. Finite mixture models methodology was applied to generate clinical clusters and mean longitudinal responses were compared between secukinumab doses (300 vs 150 mg) across identified clusters and clinical indicators through week 52 using machine learning (ML) techniques. RESULTS: Seven distinct patient clusters were identified. Cluster 1 (very-high (VH) - SWO/TEN (swollen/tender); n=187) was characterised by VH polyarticular burden for both tenderness and swelling of joints, while cluster 2 (H (high) - TEN; n=251) was marked by high polyarticular burden in tender joints and cluster 3 (H - Feet - Dactylitis; n=175) by high burden in joints of feet and dactylitis. For cluster 4 (L (Low) - Nails - Skin; n=209), cluster 5 (L - skin; n=283), cluster 6 (L - Nails; n=294) and cluster 7 (L; n=495) articular burden was low but nail and skin involvement was variable, with cluster 7 marked by mild disease activity across all domains. Greater improvements in the longitudinal responses for enthesitis in cluster 2, enthesitis and Psoriasis Area and Severity Index (PASI) in cluster 4 and PASI in cluster 6 were shown for secukinumab 300 mg compared with 150 mg. CONCLUSIONS: PsA clusters identified by ML follow variable response trajectories indicating their potential to predict precise impact on patients' outcomes. TRIAL REGISTRATION NUMBERS: NCT01752634, NCT01989468, NCT02294227, NCT02404350.

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RMD Open

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7

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3

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© Author(s) (or their employer(s)) 2021. 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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Clinical sciences

Science & Technology

Life Sciences & Biomedicine

Rheumatology

arthritis

biological therapy

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Pournara, E; Kormaksson, M; Nash, P; Ritchlin, CT; Kirkham, BW; Ligozio, G; Pricop, L; Ogdie, A; Coates, LC; Schett, G; McInnes, IB, Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis, RMD Open, 2021, 7 (3), pp. 001845

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