Table 1.

Primary, secondary and exploratory objectives for the OPTIMISE trial

Objectives	Outcome measures	Timepoint(s) of evaluation of this outcome measure (if applicable)
Primary objective To test whether the clinical response to TNF and IL-17A inhibitor therapy in participants with PsA differs according to the level of baseline activated Th17 cells.	Clinical response as measured by the minimal disease activity (MDA) criteria	Immunophenotype data at baseline and clinical response at week 24.
Secondary objectives To test whether the clinical response to TNF and IL-17A inhibitor therapy in participants with PsA differs according to intracellular IL-17 levels.	Clinical response as measured by the MDA criteria	Immunophenotype data at baseline and clinical response at week 12/16 and week 24.
To understand if the activated Th17 surface and intracellular signature resolves after treatment with IL-17A blockade and how it is altered after TNF blockade.	Activated Th17 proportion and intracellular levels of IL-17	Immunophenotype data at baseline and week 24.
To understand if changes in the activated Th17 surface and intracellular signature differ in treatment responders and non-responders.	Clinical response as measured by the MDA criteria.	Clinical disease pattern and Immunophenotype data at baseline and clinical response at week 12/16 and week 24.
To explore if the immune subset-specific transcriptomic signature can be used to predict response to IL-17A and TNF blocking therapies either alone or in combination with the activated surface and intracellular Th17 signatures.	Clinical response as measured by the MDA criteria.	Clinical disease pattern and Immunophenotype data at baseline and clinical response at week 12/16 and week 24.
To explore if any of the baseline immune signatures are associated with response in different PsA tissues	Clinical response in PsA tissues including joint counts, enthesitis, dactylitis, skin and nail disease scores and in overall disease as measured by the PsA disease activity score (PASDAS).	Immunophenotype data at baseline and clinical response at week 12/16 and 24.
To explore if any of the baseline immune signatures are associated with response and disease impact from the patients’ perspective	Response as measured by patient reported outcomes including PsAID, SF36 and WPAI	Immunophenotype data at baseline and clinical response at week 12/16 and 24.
To use the immune subset-specific transcriptomic signature to identify a limited number to of transcriptomic biomarkers that can be validated in whole blood.	Cell-specific transcriptomic data and whole blood transcriptomes	Immunophenotype data at baseline and week 24.
To use the immune subset-specific transcriptomic signature to define the pathways driving biologic-refractory disease.	Cell-specific transcriptomic data and whole blood transcriptomes	Immunophenotype data at baseline and week 24.
Exploratory objectives To use machine learning and predictive modelling to combine baseline clinical phenotypic markers such as disease duration and clinical expression of disease with additional immunophenotypic (intracellular CD4 Th17 frequency, CD8 Tc17 frequency, MAIT cell frequency, immune transcriptomic signature) factors to develop a predictive model for response to IL-17A and/or TNF inhibitor therapy in PsA.	Clinical response as measured by the MDA criteria.	Clinical disease pattern and Immunophenotype data at baseline and clinical response at week 24.
To test whether the clinical response to TNF and IL-17A inhibitor therapy in participants with PsA differs according to the level of baseline activated Th17 cells.	Clinical response as measured by the MDA criteria	Immunophenotype data at baseline and clinical response at week 12/16.
To explore if the change or absolute levels of activated Th17 surface and intracellular signature or the transcriptomics at week 4 can predict response to IL-17A and TNF blocking therapies	Clinical response as measured by the MDA criteria.	Immunophenotype data at baseline and 4 weeks and clinical response at week 12/16 and 24.

SF-36 = short form 36

OPTIMISE, Optimising Psoriatic arthritis Therapy with Immunological Methods to Increase Standard Evaluation; PsA, psoriatic arthritis; TNF, target tumour necrosis factor; WPAI, work productivity and activity impairment.