P153 Exploring the relationships between objective and subjective clinical measures in Sjogren's Syndrome
Authors: Berry Joe S , Tarn Jessica , Lendrem Dennis , Casement John , Ng Wan-Fai 
Published: April 2024

Background/Aims

Patient Reported Outcome Measures (PROMs) are standardised, validated questionnaires designed to measure the patient’s perception of their disease. Discordance between the patient’s perspective and objective clinical measures (clinical scores, laboratory data) has led to increased interest in PROMs in Sjogren’s syndrome (SS). Initial concern about the subjectivity of PROMs has given way to methodological rigour and clear guidance for the development of PROMs. Several studies have now used PROMs for symptom-based stratification, and recently researchers have developed composite disease assessment tools incorporating PROMs and objective clinical measures to create more clinically meaningful endpoints for SS trials. With the advent of PROM-based stratification tools and composite endpoints, it is vital to better understand the relationship between clinical measures in SS. In this project we performed network analysis with data from a large cohort of well-characterised SS patient to improve our understanding of the relationship between objectively measured parameters and PROMs.

Methods

The UK Primary Sjogren’s Syndrome Registry (UKPSSR) is a nationwide observational cohort of primary SS patients who fulfil the 2002 American European Consensus Group classification criteria. The UKPSSR holds detailed clinical and laboratory data that is collected prospectively, including patient-reported outcomes collected using standardized questionnaires. To assess concordance between clinical measures we used the ARACNE algorithm, which calculates mutual information between the variables of a multidimensional dataset to construct a network of shared information. Statistical analysis was performed in R-v4.1.3 and JMP Pro-v15 and network visualisation in Cytoscape-v3.8.2.

Results

The ARACNE network highlights key areas of concordance and discordance between PROMs, clinician-based and laboratory-based measurements. Providing assurance to this approach, multi-domain PROMs and ESSDAI (EULAR Sjögren's syndrome disease activity index) subdomains are strongly associated with their component scores and different PROMs measuring the same symptoms were also correlated. In contrast, there is a clear separation between PROMs, clinician-based and laboratory-based measurements each forming their own sub-networks. Furthermore, most laboratory measurements do not have strong relationship with clinician-based disease activity score or PROMs. EQ-5D utility and HADS (Hospital Anxiety and Depression Scale) values provide the primary link between ESSPRI (EULAR Sjogren's Syndrome Patient Reported Index) and ESSDAI subdomain scores and both ESSDAI and ESSPRI are important contributors to quality-of-life.

Conclusion

The dissociation between PROMs and objective clinical measures is important for clinical management and trial design. Whilst it complicates clinical management of SS including any treat-to-target strategy; it highlights the importance of PROMs in supporting clinician assessment and laboratory measurements to better capture all aspects of SS and give a more individualised, meaningful assessment. Finally, it supports the dual-target strategy of systemically pursuing two targets in the design of clinical trials: one focused on the disease activity and another focused on the symptoms and impact.

Disclosure

J.S. Berry: None. J. Tarn: None. D. Lendrem: None. J. Casement: None. W. Ng: Consultancies; Expert advice in the area of Sjogren’s syndrome to GlaxoSmithKline, MedImmune, UCB, Abbvie, Roche, Eli Lilly, Takeda, Resolves Therapeutics, Sanofi, Novartis and BMS.