Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis

Ooms, A. et al. (2023) Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis. BMJ Open, 13(9), e078539. (doi: 10.1136/bmjopen-2023-078539) (PMID:37770264) (PMCID:PMC10546161)

Abstract

Introduction: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response. This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. Methods and analysis: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. Ethics and dissemination: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. Trial registration number ISRCTN17228602.

• Item Type: Articles
• Additional Information: Funding: The OPTIMISE study is funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) grant number NIHR129023. The research is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Bennett, Dr Louise and Tulunay Virlan, Dr Aysin and Siebert, Professor Stefan and Goodyear, Professor Carl
• Authors: Ooms, A., Al-Mossawi, H., Bennett, L., Bogale, M., Bowness, P., Francis, A., Goodyear, C., Kirkham, B. W., Lalnunhlimi, S., McInnes, I. B., Richards, D., Siebert, S., Taams, L. S., Tulunay Virlan, A., Yager, N., and Coates, L. C.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: BMJ Open
• Publisher: BMJ Publishing Group
• ISSN: 2044-6055
• ISSN (Online): 2044-6055
• Published Online: 28 September 2023
• Copyright Holders: Copyright © Author(s) (or their employer(s)) 2023
• First Published: First published in BMJ Open 13(9):e078539
• Publisher Policy: Reproduced under a Creative Commons license