Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti-TNF-refractory Crohn's disease

Background Anti-tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. Both ustekinumab and vedolizumab are used in this setting but there are few data on comparative effectiveness. Aim To compare the effectiveness of ustekinumab and vedolizumab in anti-TNF-refractory Crohn's disease over 12 months. Methods Patients commencing ustekinumab or vedolizumab for anti-TNF-refractory Crohn's disease with minimum follow-up of 12 months were included. Disease activity was monitored serially with the Harvey-Bradshaw Index. Faecal calprotectin was recorded at baseline and follow-up, if available. The primary outcome measure was the difference in steroid-free remission rates at end of induction (2 months) and at 12 months. We adjusted for confounders using propensity score-matched analysis weighted by the inverse predicted probability of patients' observed treatment. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid-free remission and clinical response and remission. Results We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. Baseline variables were comparable between the two groups. In an unadjusted model, rates of steroid-free and clinical remission were significantly higher among ustekinumab-treated patients. After adjusting for confounders, steroid-free remission was higher among ustekinumab-treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06-7.39,P = 0.038) and 12 months (OR 2.01, 95% CI 0.89-4.56,P = 0.095). In a logistic regression model, prior exposure to two anti-TNF agents was associated with lower probability of steroid-free remission (OR 0.27, 95% CI 01-0.74,P = 0.011) and clinical remission (OR 0.32, 95% CI 0.12-0.86,P = 0.024) at 12 months. There was a significant reduction in Harvey-Bradshaw Index and faecal calprotectin from baseline in both groups; ustekinumab was associated with greater reduction in Harvey-Bradshaw Index (OR -2.72, 95% CI -4.2 to -1.124,P < 0.001). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%,P = 0.007). Conclusions Ustekinumab appeared more effective in treating anti-TNF-refractory Crohn's disease and more patients persisted with therapy.