Background/Purpose: Although patient stratification can improve the success rate of clinical trials, efforts to apply this strategy to autoimmune studies such as Sjögren’s syndrome are hindered by the nature of this disease area, intra-disease patient diversity, difficulties around diagnostic criteria and response metrics, as well as the lack of clear biological mechanisms to explain drug efficacy. In some of the diseases, the nexus of these variables is B-cell biology.

Methods: The ImmunoSignature Technology — the semi-quantitative profile of antibody binding specificity — is designed to enable patient stratification in autoimmune disease trials. HealthTell’s unique approach to peptide microarray fabrication, combining silicon wafer-based photolithographic synthesis with optimized peptide coupling chemistry and MALDI-based quality control, permits high-throughput ImmunoSignaturing with exceptional scalability, reproducibility and accuracy, making it broadly-applicable to diagnostic, clinical and discovery applications. In this study, HealthTell’s ImmunoSignature platform was applied to key steps in a clinical trial (NCT02149420) with VAY736, an anti-B cell activating factor (BAFF) receptor monoclonal antibody, in patients with primary Sjögren’s Syndrome.

Results: The ImmunoSignature distinguished Sjögren’s patients from healthy volunteers with an AUC of 0.84, with individual peptides showing a correlation to the EULAR Sjögren’s syndrome disease activity index (ESSDAI) of up to 0.74 (Pearson’s r). Using serum collected prior to treatment, the ImmunoSignature predicted which patients will respond to study drug with a drop in ESSDAI of ≥3, yielding an AUC of 0.75 from a small study (18 treated patients with 9 placebo). Response to therapy performance was also measured using sera drawn 12 weeks post treatment and resulted in an AUC of 0.84. Using the 12-week sample, principle component analysis correctly segregated drug-treated responders from drug-treated non-responders, placebo non-responders and the single placebo-responsive patient. Alignment of the peptides that comprise these contrasts to the human proteome yields not only known Sjögren’s autoantigens but also potential novel biomarkers.

Conclusion: The Immunosignature identified in this study is important for disease diagnosis and explanation of study drug response.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunosignature-based-diagnosis-and-prediction-of-therapeutic-response-enables-retrospective-patient-stratification-in-a-phase-iia-clinical-trial-for-vay736-in-primary-sjogrens-syndrome/