FRI0381 TROUGH SERUM DRUG LEVELS AND DISEASE ACTIVITY IN AXIAL SPONDYLOARTHRITIS PATIENTS ON LONG-TERM TREATMENT WITH TNF-α INHIBITORS
Authors: Liseth de Wolff, Suzanne Arends, Freke Wink, Elisabeth Brouwer, Anneke Spoorenberg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In approximately 50% of patients with axial spondyloarthritis (ax-SpA) treated with TNF-α inhibitors, treatment loses efficacy after a period of time.<sup>1</sup> Previous research has shown that high disease activity is associated with low serum drug levels after 6 months of treatment with TNF-α inhibitors.<sup>2</sup> There is limited literature regarding this subject in axial SpA patients on long-term treatment with TNF-α inhibitors. <h3>Objectives</h3> To investigate the association between trough serum drug level of TNF-α inhibitors and disease activity in axial SpA patients. <h3>Methods</h3> All consecutive ax-SpA patients of the Groningen Leeuwarden Axial SpA (GLAS) cohort, fulfilling the ASAS classification criteria, treated with TNF-α inhibitors and visiting the out-patient clinic in Groningen between the 1<sup>st</sup> of June 2015 until the 31<sup>st</sup> of May 2016 were approached to have a trough serum drug level measurement within two months from the out-patient visit. Serum trough levels were stratified in a 'therapeutic' and 'below-therapeutic' range according to the reference values of Sanquin<sup>3</sup>. Disease activity was assessed with the ASDAS, BASDAI and CRP. <h3>Results</h3> 67 (60%) of the 112 approached patients were eligible for analyses. Thirty-one (46%) were male, mean age was 45±12 years, 48 patients (72%) were HLA-B27 positive, mean symptom duration was 20±12 years and median duration of TNF-α inhibitor treatment was 49 months (IQR 14-64). 34 patients were on adalimumab (51%), followed by 21 on etanercept (31%) and the remaining 12 patients (18%) were on infliximab, certolizumab or golimumab. 32 of the 67 patients (48%) had a 'therapeutic' serum trough drug level and 35 (52%) were 'below-therapeutic', with no significant difference in patient characteristics between these 2 groups, including disease activity (ASDAS 2.2±1.0 vs. 2.3±0.8; BASDAI 3.9±2.4 vs. 4.1±2.1; CRP 4.5, IQR 2.0-6.6 vs. 3.0, IQR 2.0-6.0). No significant correlations for ASDAS, BASDAI and CRP with adalimumab or etanercept drug level were found (adalimumab r=-0.164, p=0.36; r=-0.191, p=0.29; r=-0.041, p=0.83 resp.; etanercept r=-0.185, p=0.42; r=-0.113, p=0.63; r=-0.216, p=0.36 resp.). Stratified by gender, only women on adalimumab showed a weak significant negative correlation between serum level and ASDAS and BASDAI (r=-0.444, p&lt;0.05; r=-0.497, p&lt;0.05 resp.) but not for CRP (r=0.038, p=0.87). Compared to men, women had a significantly higher ASDAS and CRP. BASDAI was not significantly different (data not shown). Patient characteristics between patients with and without serum trough level measurements did not differ significantly. <h3>Conclusion</h3> In daily clinical practice random serum trough levels in ax-SpA patients are relatively low according to reference values of Sanquin. Furthermore, only for women on adalimumab a weak correlation was found between trough serum drug level and ASDAS and BASDAI but not for CRP. <h3>References</h3> [1] Arends S., Brouwer E., Efde M. et al. Long-term drug survival and clinical effectiveness of etanercept treatment in patients with ankylosing spondylitis in daily clinical practice. Clin Exp Rheumatol2017;35:61-68. [2] Kneepkens E.L., Wei J.C.C., Nurmohamed M.T, et al. Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis patients during 24 weeks of follow-up. Ann Rheum Dis2015;74:396-401. [3] Sanquin Amsterdam. Diagnostische testen. Available via: www.sanquin.org/nl/producten-en-diensten/diagnostiek/diagnostische-testen/index. Consulted on April 28th 2018. <h3>Disclosure of Interests</h3> Liseth de Wolff: None declared, Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Freke Wink Consultant for: Abbvie, Janssen, Elisabeth Brouwer Speakers bureau: Dr. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche which were paid to the UMCG, Anneke Spoorenberg Grant/research support from: Received unrestricted grants from Pfizer, Novartis and Abbvie pharmaceuticals. They had no influence in design and conduct of the study., Consultant for: Abbvie, Pfizer, MSD, UCB, and Novartis