LAUSR

TNF-α inhibitors (TNFi) are widely used in axial spondyloarthritis (axSpA) patients with active disease. Approximately half of patients stop TNFi treatment, often due to loss of treatment efficacy.1 TNFi serum trough levels have been associated with initial therapeutic response in axSpA patients.2 Additionally, a relation was found between serum trough TNFi levels and BMI.3To explore in axSpA patients on long-term TNFi therapy associations between randomly measured TNFi serum trough levels, disease activity and BMI.Patients from the UMCG on adalimumab or etanercept and a regular visit in the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were approached for a random TNFi serum trough level measurement. Based on reference values of Sanquin3, serum trough levels were stratified in therapeutic and below therapeutic levels. The Ankylosing Spondylitis Disease Activity Score (ASDAS) from a regular outpatient GLAS visit was used for analyses, if assessed <2 months of the serum trough level measurement. Active disease according to ASDAS was defined as ≥2.1. Correlations and univariable logistic regression were performed. Multivariable logistic regression was performed to correct the relation between therapeutic drug levels and ASDAS for potential confounders.94 axSpA patients on adalimumab or etanercept were approached for a random TNFi serum trough level measurement, of which 55 (59%) had a measurement taken. See Table 1 for patient characteristics. No significant correlations were found for adalimumab or etanercept serum trough levels (as continuous variable) with ASDAS (adalimumab: r=-0.16, p=0.39; etanercept: r=-0.29, p=0.20). According to Sanquin definitions of therapeutic TNFi levels, 26 patients (47%) had therapeutic serum trough levels: 19/34 (56%) for adalimumab and 7/21 (33%) for etanercept. Univariable logistic regression showed no significant associations between therapeutic levels (yes/no) and ASDAS. In multivariable analyses, BMI was identified as the only confounder for the relationship between therapeutic drug levels and ASDAS. Median BMI was higher, although not statistically significant, in patients with below-therapeutic serum trough levels compared to therapeutic levels (27.1, IQR 24.6-31.7 vs. 24.3, IQR 22.7-31.4, p=0.08). Furthermore, BMI had a significant, negative correlation with adalimumab and etanercept serum levels (adalimumab: r=-0.48, p=0.01, etanercept: r=-0.46, p=0.04) (Figure 1). Patients with active disease according to ASDAS had higher BMI than patients with inactive disease (median 29.7 vs. 24.5, p=0.01).In this cross-sectional, observational study of axSpA patients on long-term TNFi treatment, BMI was significantly correlated with adalimumab and etanercept serum trough levels. Furthermore, BMI was significantly higher in patients with active disease. Therefore, overweight /obese patients on TNFi treatment and active disease, might benefit from an increase in TNFi dose.[1]Arends et al, Clin Exp Rheumatol 2017;35:61-68[2]Kneepkens et al, Ann Rheum Dis 2015;74:396-401[3]Rosas et al, Clin Exp Rheum 2017;35:145-148[4]Sanquin Amsterdam. Diagnostic tests. Available via: www.sanquin.org/nl/producten-en-diensten/diagnostiek/diagnostische-testen/indexTable 1.Characteristics of 55 axSpA patients with random adalimumab or etanercept serum trough level measurementsAdalimumab (n=34)Etanercept (n=21)Age (years)45 ± 1346 ± 12Gender (male)14 (41)12 (57)BMI (kg/m2)26.6 (24.5-32.7)24.3 (21.9-29.5)*Symptom duration (years)21 ± 1420 ± 8HLA-B27 positive26 (79)16 (84)ASDAS2.3 (1.7-3.1)1.6 (1.3-2.0)**Treatment duration current TNFi (months)27 (7-57)58 (12-76)Serum trough level (μg/ml)5.2 (3.7-8.0)1.6 (1.1-2.4)Values are mean ± SD, median (IQR) or n (%)*Significant difference (p<0.05) and **(p<0.01) compared to patients on adalimumabFigure 1.Scatterplot of BMI and serum trough level of adalimumab (A) and of etanercept (B)Liseth de Wolff: None declared., Suzanne Arends Grant/research support from: Pfizer, Elisabeth Brouwer Grant/research support from: Pfizer, Hendrika Bootsma: None declared., Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, Novartis and UCB, Grant/research support from: Abbvie, Pfizer and Novartis.