OBJECTIVE: Biological agents have shown markedly different response rates by baseline C-reactive protein (CRP). Here, we determine the response of patients with nonradiographic axial spondyloarthritis (nr-axSpA) to etanercept stratified by their baseline CRP level. METHODS: The EMBARK trial was a phase 3, randomized, double-blind, placebo-controlled study of etanercept in nr-axSpA. The primary endpoint was Assessment of Spondyloarthritis International Society (ASAS) 40 at Week 12, the conclusion of the double-blind phase. It recruited patients who met the ASAS criteria for axial spondyloarthritis, and sacroiliac joint magnetic resonance scans were completed on all patients. In this post hoc analysis, we analyzed outcomes by baseline C-reactive protein (CRP) level of less than 5 mg/L, 5 mg/L to 10 mg/L, and greater than 10 mg/L. The clinical trial outcome data were accessed via the Vivli platform. RESULTS: In the less than 5 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP), and ASDAS-ESR (erythrocyte sedimentation rate) outcomes were 49% (P = 0.84), 26% (P = 0.14), 42% (P = 0.002), and 44% (P = 0.006), respectively. In the 5 to 10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS-CRP, and ASDAS-ESR outcomes were 56% (P = 0.99), 31% (P = 0.40), 56% (P = 0.16), and 50% (P = 0.11), respectively. In the greater than10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS-CRP, and ASDAS-ESR outcomes were 74% (P = 0.02), 68% (P = 0.003), 82% (P = 0.005), and 50% (P = 0.001), respectively. CONCLUSION: Although there are reduced ASAS20 and ASAS40 response rates in the groups with baseline CRP less than 10 mg/L, there remain clinically relevant responses when the composite outcome measures ASDAS-CRP or ASDAS-ESR were used, and this should be considered when deciding on thresholds for reimbursement.