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Background Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life. Methods Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence of relapse over time were assessed by survival curves. Cox-regression analysis was performed to identify predictive factors of tofacitinib discontinuation or relapse over time. Data quality was assessed by remote monitoring. Results 113 patients were included (Table 1 and Figure 1) and exposed to tofacitinib a median of 44 (interquartile range = 30–66) weeks. Response and remission at week 8 were 60% and 31%, respectively (Figure 2). In multivariate analysis, higher PMS at week 4 [odds ratio (OR)=0.2; 95% confidence interval (CI) = 0.1–0.4] was the only variable associated with the likeliness of achieving remission at week 8. Higher PMS at week 4 (OR = 0.5; 95% CI = 0.3–0.7) and higher PMS at week 8 (OR = 0.2; 95% CI = 0.1–0.5) were associated with lower probability of achieving remission at week 16. Twenty per cent of those without remission at week 4, and 12% of those without remission at week 8, achieved remission at week 16. A total of 45 patients (40%) discontinued tofacitinib over time (Figure 3); the discontinuation rate was 34% and 46% at 24 and 52 weeks, respectively. PMS at week 8 was the only factor associated with tofacitinib discontinuation [Hazard ratio (HR) = 1.5; 95% CI = 1.3–1.6)]. A total of 33 patients had remission at week 8; from them, 65% relapsed 52 weeks after achieving remission; 9 patients increased the dose to 10 mg /12 h and 5 reached remission again. No factors associated with relapse over time were identified. Eighteen patients had adverse events (4 hypercholesterolaemia, 2 herpes zoster, 3 infections, 2 dyspnoea, 1 neoplasia, 1 lymphopenia, 1 headache, 1 hypertriglyceridaemia and 4 others). No thromboembolic events were reported. Conclusion Tofacitinib is relatively effective in UC patients in real practice even in a highly refractory cohort. Only 10% of the patients without remission at week 8 reached remission at week 16. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure. Over 60% of patients that achieve remission, relapse over time. Safety was consistent with the known profile of tofacitinib

Background Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring. Results Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to >2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant). Conclusion Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.