OP0026 Adalimumab serum concentration fails to predict achievement of sustained remission or absence of flare for patients with non-radiographic axial spondyloarthritis in the ability-3 study
Authors: N.V. Kwatra, M. Magrey, P.J. Mease, J. Sieper, R. Landewe, X. Wang, A. Lertratanakul, J.K. Anderson, N.M. Mostafa
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In patients (pts) with active non-radiographic axial spondyloarthritis (nr-axSpA) in the ABILITY-3 study who achieved sustained remission with adalimumab (ADA), continued ADA therapy was associated with significantly fewer pts flaring than treatment withdrawal. Sustained remission is an important treatment goal in pts with nr-axSpA, but factors predicting sustained remission and absence of flare are unknown. <h3>Objectives</h3> To determine whether an ADA concentration threshold is predictive of achievement of sustained remission and absence of flare in pts with nr-axSpA. <h3>Methods</h3> ABILITY-3 included a 28-wk open-label (OL) ADA (40 mg every other wk) lead-in in which pts who achieved sustained remission (ASDAS &lt;1.3 at wks 16, 20, 24, and 28) were randomised to double-blind (DB) placebo (PBO) or continued ADA for 40 wks (68 wks total). Pts not achieving remission were discontinued at wks 20, 24, or 28. The primary efficacy variable was the proportion of pts who did not experience a flare (ASDAS ≥2.1 at 2 consecutive visits) by wk 68. Pts who flared received OL ADA rescue. ADA trough concentrations at wks 12 or 28 were used to predict achieving sustained remission by wk 28 (all OL patients, n=673) and absence of flare at wk 68 (patients randomised to DB ADA, n=152). Threshold analysis was conducted by constructing receiver operating characteristic (ROC) curves (R Ver 3.3.3) to assess predictive ADA trough concentration thresholds based on specificity and sensitivity values. <h3>Results</h3> Of 673 pts enrolled in the OL phase, 305 met criteria for remission at wk 28 and were randomised to DB treatment. Mean ±SD ADA trough concentrations were 6.68±5.23 µg/mL at wk 12 and 8.36±5.27 µg/mL at wk 28. During the DB phase, 81 and 45 pts flared and 68 and 36 pts received ≥12 wks of OL ADA rescue in PBO (n=153) and ADA (n=152) arms, respectively. ADA mean ±SD trough concentration at wk 68 for pts randomised to DB ADA with flare (7.64±5.22 µg/mL) was slightly lower than for DB ADA pts without flare (8.12±4.35 µg/mL). ROC curves showed AUC values≤0.6 for achieving sustained remission by wk 28 and absence of flare at wk 68, with no concentration threshold meeting sensitivity and specificity criteria for reliable prediction of such endpoints (figure 1). <h3>Conclusions</h3> ROC analyses did not identify an ADA trough concentration threshold that reliably predicted whether a pt with nr-axSpA would achieve sustained remission (by wk 28) or absence of flare (at wk 68). <h3>Acknowledgements</h3> AbbVie funded the study and approved the abstract for submission. Medical writing support was provided by Janet Matsuura, PhD, of Complete Publication Solutions, LLC (North Wales, PA) and was funded by AbbVie. <h3>Disclosure of Interest</h3> N. Kwatra Employee of: AbbVie, M. Magrey Grant/research support from: Amgen, AbbVie, and UCB Pharma, Consultant for: UCB and Janssen, P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, and UCB, J. Sieper Consultant for: AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB, Speakers bureau: AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos, GlaxoSmithKline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB, and Wyeth, Speakers bureau: Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, X. Wang Employee of: AbbVie, A. Lertratanakul Employee of: AbbVie, J. Anderson Employee of: AbbVie, N. Mostafa Employee of: AbbVie