RT Journal Article
SR Electronic
T1 Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis
JF RMD Open
JO RMD Open
FD EULAR
SP e001845
DO 10.1136/rmdopen-2021-001845
VO 7
IS 3
A1 Effie Pournara
A1 Matthias Kormaksson
A1 Peter Nash
A1 Christopher T Ritchlin
A1 Bruce W Kirkham
A1 Gregory Ligozio
A1 Luminita Pricop
A1 Alexis Ogdie
A1 Laura C Coates
A1 Georg Schett
A1 Iain B McInnes
YR 2021
UL http://rmdopen.bmj.com/content/7/3/e001845.abstract
AB 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, NCT02404350All data relevant to the study are included in the article or uploaded as online supplemental information. The datasets generated during and/or analysed during the current study are not publicly available. Novartis is committed to sharing with qualified external researchers’ access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved on the basis of scientific merit. All data provided is anonymised to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The data may be requested from the corresponding author of the manuscript.