SAT0385 Immunogenicity, Tnf-Inhibitors Levels and Disease Outcomes in Ankylosing Spondylitis: Results from An Observational Cohort Study
Authors: C. Ancuta, C. Pomirleanu, C. Belibou, R. Maxim, L. Petrariu, G. Strugariu, I. Esanu, R. Chirieac, E. Ancuta
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Up to one third of spondylarthritis (SpA) fail to respond to anti-TNF agents or experience drug toxicity leading to treatment withdrawal. Part of the treatment failure can be explained by the development of anti-drug antibodies (ADA). <h3>Objectives</h3> To evaluate the relation between immunogenicity, drug levels and clinical efficacy of TNF inhibitors (TNF-i) in ankylosing spondylitis (AS). <h3>Methods</h3> We performed a prospective observational study in a cohort of 47 consecutive AS patients receiving adalimumab (ADL) (13; 27.7%), infliximab (IFX) (13; 27.7%) or etanercept (ETN) (21; 44.7%). Disease Disease activity (BASDAI, ASDAS), outcomes and adverse events were evaluated at baseline and study visit, while serum TNF-i and ADA levels collected as a single-point data in both bio-naïve (37, 78.7%) and bio-experimented patients. Serum drug levels were considered positive for IFX if &gt;0.035 μg/mL, for ADL &gt;0.024 μg/mL and for ETN &gt;0.035 μg/mL, while the cut-off value for the ADA positivity to IFX was established at 5AU/ml, for ADL at 10AU/mL and ETN at 142 AU/mL (ELISA, Progenika). Statistical analysis was performed using SSPS version 19.0, p&lt;0.05 <h3>Results</h3> At baseline mean BASDAI was 7.69 and mean ASDAS-CRP 3.50, with no difference in disease activity between patients who did or did not later develop ADA (p&lt;0.05). 37 (78.7%) AS were BASDAI responders at study visit (BASDAI 1.16, ASDAS-CRP 1.73). ADA were detected in 8/47 (17%) and were more frequent in patients treated with ADL (5 cases; 38.5%) <i>vs</i> IFX (3 cases; 23.1%); no with ETN. Both ADL and IFX levels were significantly higher for ADA negative than for ADA positive patients (ADL: 3.92μg/mL <i>vs</i> 0.02μg/mL, p&lt;0.01; IFX: 1.82μg/mL <i>vs</i> 0.03 μg/mL, p&lt;0.01). A significant association between clinical activity (ASDAS) and immunogenicity (ADA status) was reported: patients who had developed ADA had higher disease activity (3.10 <i>vs</i> 1.73, p&lt;0.01), and more patients were classified as being in a high or very high disease activity status. Furthermore, a relation between clinical improvement (change in ASDAS) and immunogenicity was reported: ADA-positive AS achieved worse clinical response than ADA-negative cases, with a significant association between ADL respectively IFX levels and ASDAS (p&lt;0.05). <h3>Conclusions</h3> ADL and IFX levels are commonly influenced by ADA-positivity, and related to clinical response in AS, suggesting that therapeutic drug monitoring should be investigated as a possible tool to optimise treatment such patients. <h3>References</h3> Arstikyte I et al. Influence of Immunogenicity on the Efficacy of Long-Term Treatment with TNFα Blockers in Rheumatoid Arthritis and Spondyloarthritis Patients. BioMed Research International 2015 Hoxha A, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: A prospective multicentre study. Joint Bone Spine 2015 <h3>Disclosure of Interest</h3> None declared