Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial

<jats:sec><jats:title>Objective</jats:title><jats:p>RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal. (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link>:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT02509026">NCT02509026</jats:ext-link>)</jats:p></jats:sec>