To model the estimated disease-modifying effect of etanercept over sulphasalazine in patients with ankylosing spondylitis. A post hoc analysis of data from the Ankylosing Spondylitis Study Comparing ENbrel and Sulfasalazine Dosed Weekly (ASCEND) study was performed using the Natural History Staggered Start (NHSS) method. A mixed model with a linear effect over time was fitted to the ASCEND data and resampling was performed to generate confidence intervals. At week 16, the total additional improvement in Bath Ankylosing Spondylitis Metrology Index of the etanercept arm over the sulphasalazine arm was 0.62 points, of which 31% (0.19 points) was estimated to be due to disease-modifying effect. The analysis of ASCEND data suggests that etanercept may have a larger disease-modifying effect than sulphasalazine. Further research is needed with more objective measures such as magnetic resonance imaging or X-radiography to confirm these results.