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Objectives To study the impact of C reactive protein (CRP) level at treatment start on interleukin-17 inhibitor (IL-17i) and tumour necrosis factor inhibitor (TNFi) effectiveness, including treatment retention, in axial spondyloarthritis (axSpA).Methods Nationwide observational study including patients with axSpA from the DANBIO registry initiating their first IL-17i or first TNFi between 2015 and 2024. Outcomes were 12-month treatment retention and Bath Ankylosing Spondylitis Disease Activity Index remission stratified by CRP levels (<5 (low)/5–10 (intermediate)/>10 mg/L (high)) at treatment initiation (baseline). Kaplan-Meier plots (including substratification by sex and radiographic status) and Cox regression models were used to assess treatment retention and hazard of discontinuation for IL-17i and TNFi separately.Results Overall, 3387 patients were included (601 IL-17i, 2786 TNFi) with baseline CRP levels (low/intermediate/high) 57%/17%/26% for IL-17i and 48%/20%/32% for TNFi. For IL-17i, 95% of patients were TNFi-experienced; for TNFi, 99% were biologic-naïve.The 12-month retention rates stratified by baseline CRP (low/intermediate/high) were 51%/53%/55% for IL-17i and 63%/66%/72% for TNFi, with similar results when stratified by sex and radiographic status. Cox models (reference: low CRP) showed no clear association between CRP level and treatment retention among patients receiving IL-17i (intermediate CRP: HR 0.96, 95% CI 0.68 to 1.19; high CRP: HR 0.90, 95% CI 0.68 to 1.19). In contrast, among patients receiving TNFi, intermediate and high CRP levels were associated with a lower risk of treatment discontinuation (HR 0.86, 95% CI 0.73 to 1.02 and HR 0.72, 95% CI 0.62 to 0.84, respectively). Remission rates were 6%/8%/11% for IL-17i and 19%/22%/32% for TNFi.Conclusion In routine care, IL-17i was mainly used in biologic-experienced patients, whereas TNFi was primarily used in biologic-naïve patients with axSpA. Higher baseline CRP levels were associated with higher retention for first TNFi but not for first IL-17i. Higher CRP was associated with higher remission rates for both IL-17i and TNFi.