ObjectiveTo investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long‐term inception cohort.MethodsWe included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10‐year follow‐up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2‐year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders.ResultsIn this long‐term inception cohort, 10‐year follow‐up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2‐year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β = –0.09 [95% confidence interval (95% CI) –0.18, –0.003]; analyses adjusted for age, sex, symptom duration, HLA–B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C‐reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β = 0.05 [95% CI –0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2‐year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β = –0.16 [95% CI –0.28, –0.03] versus β = –0.04 [95% CI –0.15, 0.07]).ConclusionTreatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated.