FRI0399 INFLIXIMAB TROUGH LEVELS AND DISEASE ACTIVITY PREDICT EARLY CLINICAL RESPONSE IN PATIENTS WITH AXIAL SPONDYLOARHTRITIS
Authors: ANA MARTíNEZ-FEITO, Chamaida Plasencia, Borja Hernández-Breijo, Victoria Navarro-Compán, Diana Peiteado, Alejandro Villalva, Laura Nuño, Irene Monjo, Cristina Diego, Dora Pascual-Salcedo, Alejandro Balsa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Infliximab (Ifx) has proven to be effective in patients with axial spondyloarthritis (axSpA). Several variables may affect pharmacokinetic-pharmacodynamic of Ifx and its relation with clinical response, such as: disease activity (inflammatory burden), the development of anti-drug antibodies (ADA) and the concomitant use of conventional synthetic disease modifying anti-rheumatic drugs The improvement of patient's management by achieving optimal serum drug concentration associated with good clinical response is the main goal of therapeutic drug monitoring (which can be helpful in the prediction of clinical response to biological treatment. <h3>Objectives</h3> To identify clinical and serological variables at early stages of treatment that can predict clinical response in patients with axSpA treated with Ifx. <h3>Methods</h3> Observational study including 81 patients with axSpA recruited from the axSpA-Paz cohort treated with Ifx and monitored during 24 weeks (W). Serum Ifx levels and ADA were measured by capture ELISA and by bridging ELISA respectively at baseline, W2, W6, W14 and W24. Disease activity was assessed at baseline and W24 by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical response was defined by ΔASDAS≥1.1 (clinically important improvement). The association between clinical response at W24 and clinical and serological variables was evaluated by univariable and multivariable logistic regression analyses. Serum Ifx levels at W2, 6 and 14 as a categorical variable (above o under the corresponding median value of levels at each time week), age, sex, HLA-B27, methotrexate (MTX), sulfasalazine, body mass index, smoke status, prednisone, C-reactive protein and ASDAS at baseline were included as independent variables. Receiver operating characteristic (ROC) curves for the outcome of clinical response after 24 weeks of treatment were employed to determine the best cut-off values for the predictors (serum Ifx concentrations and baseline ASDAS). Ifx survival was evaluated through Kaplan-Meier curves. <h3>Results</h3> In the univariable analyses, higher serum Ifx trough levels at W14 (OR: 3.9; 95%CI: 1.5-10.4); higher baseline ASDAS (OR: 1.9; 95%CI: 1.1-3.1) and MTX use (OR: 3.3; 95%CI: 1.2-8.7) were associated with a better clinical response at W24. Patients with concomitant MTX had higher serum Ifx trough levels (median and IQR) than patients without MTX and these differences were significant at W6: 26.37(16-41.4) versus 16.9(11.4-26.9); p=0.008; at W14: 8.4(5.4-13.9) versus 4.1(1.8-7.8); p=0.003 and at W22: 5.1(2.2-8.3) versus 3.1(0.6-5.4); p=0.006 and; respectively). In the multivariable analysis, higher ASDAS at baseline (OR: 1.8; CI 95%: 1.1-3.0) and higher serum Ifx trough levels at W14 (OR: 3.6; CI 95%: 1.3-10.4) remained significantly associated. Serum Ifx concentration at W14 ≥ 6.7 μg/mL and a disease activity score at baseline ≥ 3.5 were found to be associated with higher ΔASDAS at W24 (OR: 16; 95%CI: 3.6-71.7). No patient with Ifx levels at W14 ≥ 6.7 μg/mL developed ADA during the 24 weeks follow up. The combination of both variables was used to predict clinical response with a sensitivity of 87.5%, specificity of 69.6%, PPV of 75% and NPV of 84.2%. <h3>Conclusion</h3> Elevated baseline ASDAS and high serum Ifx trough levels at W14 are associated with better clinical response at 24 weeks in patients with axSpA under Ifx therapy. A predictive model based on these variables is suggested to identify early responders to Ifx treatment. <h3>Disclosure of Interests</h3> ANA MARTíNEZ-FEITO: None declared, Chamaida Plasencia Speakers bureau: Pfizer, MSD, Borja Hernández-Breijo: None declared, Victoria Navarro-Compán: None declared, Diana Peiteado: None declared, Alejandro Villalva: None declared, Laura Nuño: None declared, Irene Monjo: None declared, Cristina Diego: None declared, DORA PASCUAL-SALCEDO Grant/research support from: Pfizer, Speakers bureau: Pfizer, Abbvie, Takeda, Alejandro Balsa Grant/research support from: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Consultant for: Abbvie, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, Paid instructor for: Pfizer, Speakers bureau: Pfizer, Novartis, UCB, Nordic, Sanofi, Sandoz, Lilly