THE BIOEFFICACY SPA PROTOCOL: BIOMARKERS OF TUMOR NECROSIS FACTOR INHIBITORS EFFICACY IN ANKYLOSING SPONDYLITIS PATIENTS USING A TRANSCRIPTOME ANALYSIS AND MASS SPECTROMETRY.

Background: Ankylosing Spondylitis (AS) is the prototypic disease of the seronegative spondyloarthritis. Inflammatory back pain is a characteristic symptom, and new bone formation with syndesmophytes and ankylosis is the hallmark of this condition, which. typically affects young people and leads to deterioration of physical function and quality of life. The introduction of biological therapies has changed clinical practice impacted significant improvement in quality of life and prognosis. However, about 40% of patients do not present an adequate response. The identification of biomarkers of treatment response would greatly benefit clinical management by targeting these treatments to those most likely to respond. Methods: Bioefficacy SpA is an investigator-initiated prospective, single-arm, open-label, multicentric trial, involving 7 national Rheumatology departments. Patients older than 18 years, with the diagnosis of Ankylosing Spondylitis (AS) (1984 modified New York Criteria, allowing the diagnosis of sacroiliitis by magnetic resonance imaging (MRI) and active disease despite optimal conventional treatment (Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - December 2011 update), were included. All patients started a tumor necrosis factor inhibitor (TNFi), adalimumab, and were follow-up for a period of 14 weeks. The primary outcome of this trial was to identify new candidate genes/proteins that are differentially expressed in responders vs non-responders to TNFi, using transcriptomic and proteomic approaches, and explore their ability to predict TNFi response. Key secondary outcomes included: composite indexes for disease activity-Assessment of Spondyloarthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS); Disease function-Bath Disease Ankylosing Spondylitis Functional Index (BASFI) and severity-Bath Ankylosing Metrology Spondylitis Index (BASMI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); general quality of life (QoL) assessment-36-Item Short Form Survey (SF-36) and EuroQoL 5 dimensions Questionnaire (EQ-5D); disease specific QoL assessment-Health Assessment Questionnaire for AS (HAQ-AS) and Ankylosing Spondylitis Quality of Life Questionnaire (ASQOL), psychological impact-Hospital Anxiety and Depression Scale (HADS); MRI changes under TNFi. At week 14, patients were classified as responder vs nonresponder according to ASAS20 achievement. Results/Conclusions: The results from Bioefficacy SpA are expected to have implications in clinical practice, allowing the development of an algorithm to identify the best candidates to TNFi therapy. Bioefficacy SpA will also contribute to understand the impact of TNFi therapy on axial spine and muscle through MRI assessment. This trial was registered in the clinical trials. gov database (https://www.clinicaltrials.gov/NCT02492217). [ABSTRACT FROM AUTHOR]