Abstract Background/Aims People with axial spondyloarthritis (axSpA) typically present with persistent back pain and experience up to a 10-year diagnostic delay that may lead to irreversible spinal damage. A multiplex assay using 14-3-3η autoantibodies (AAbs) has been developed to differentiate patients with axSpA from those with mechanical backpain (MBP). This is a high clinical unmet need for timely primary care referral of patients to a rheumatologist to reduce diagnostic delay. This study examines the discriminative performance of 14-3-3η AAbs in patients with axSpA, including those with radiographic (r-) and non-radiographic (nr-) disease, compared to people with MBP. Methods Patient serum (n = 160) from the Bath Spondyloarthritis Biobank of patients referred for suspected or confirmed axSpA during routine clinical visits were selected based on sample availability. Patients had a rheumatologist confirmed diagnosis and met classification criteria for r-axSpA (modified New York criteria, n = 55), nr-axSpA (ASAS 2009 criteria, n = 54) or MBP (n = 51). 14-3-3η AAb levels were measured using the multiplex assay. Logistic regression was performed to model the relationship between predictor variables and diagnosis. The probability formula generated from this regression was used to calculate a linear score for three models alongside variables of age, sex, CRP and HLA-B27: 1) all patients with axSpA (n = 109), 2) r-axSpA, and 3) nr-axSpA versus MBP as a control group. The r-axSpA versus MBP regression was used to calculate 14-3-3η AAb scores in banked serum samples from healthy individuals (n = 100) for comparison. Statistical significance was set at p 0.05. Results Mean age (SD) was 55(23) yrs for r-axSpA, 42(14) yrs for nr-axSpA, and 30(14) yrs for MBP. Gender distribution (%male) was respectively 67%, 41%, and 59%. Disease duration (SD) was 13(27) yrs for r-axSpA, and 5(5) yrs for nr-axSpA. HLA-B27+ status was: 69% for r-axSpA, 72% for nr-axSpA, and 18% for MBP. 14-3-3η AAb predictive model ROC AUCs for all axSpA versus MBP were 0.77, r-axSpA of 0.78 and nr-axSpA 0.73. Selecting the best sensitivity (SN) for ∼90% specificity (SP) returned SP 0.99. Conclusion The 14-3-3η AAb biomarker differentiates radiographic and non-radiographic-axSpA from MBP, achieves a high PPV and its discrimination improves when age, sex, CRP, and HLA-B27 are added. Alongside these easily accessible patient variables at primary care, 14-3-3η AAb may reduce diagnostic delay and complement HLA-B27. Disclosure R. Sengupta: Consultancies; Biogen, Bristol Myers Squibb (BMS), Abbvie, Pfizer, Novartis, Eli-Lilly, University College Bath (UCB). Honoraria; Augurex Life Sciences Corp. A. Marotta: Shareholder/stock ownership; Augurex Life Sciences Corp. W.P. Maksymowych: Consultancies; Abbvie, Eli-Lilly, Novartis, Pfizer, University College Bath, Bristol Myers Squibb (BMS), Celgene, Galapagos. C.P. Cavill: None. S. Bleakley: Corporate appointments; Augurex Life Sciences Corp. N. Biln: Shareholder/stock ownership; Augurex Life Sciences Corp.
Sengupta et al. (Wed,) studied this question.