Benefit-risk of upadacitinib in patients with moderately to severe ulcerative colitis (uc)

Introduction

Here, key safety and efficacy data from the maintenance study of Upadacitinib (UPA) phase 3 clinical trial in UC are summarized.

Aims and Methods

Patients with a clinical response (per Adapted Mayo score) after 8 weeks induction with UPA 45 mg OD were re-randomized in maintenance to receive UPA 15 mg OD, UPA 30 mg OD, or placebo (PBO). For efficacy outcomes, point estimates and 95% confidence intervals (CI) of the PBO-adjusted treatment effect were calculated. For the risk analysis, exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) were evaluated.

Results

Primary endpoint of clinical remission at Week 52 were 30.1% (95% CI: 22.7, 37.4) with UPA 15 mg and 42.9% (35.4, 50.4) with UPA 30 mg (p<0.001 for both; table 1). All secondary endpoints were significantly different. Serious infections were 5.9 E/100 PY with PBO vs 5.0 and 3.2 with UPA 15 mg and30 mg, respectively. Herpes Zoster with UPA 15 mg and 30 mg were 6.0 and 7.3 E/100 PY, respectively versus 0 in placebo. Malignancy excluding non-melanoma skin cancer were 0.7 E/100 PY with PBO vs 0.5 and 0.9 with UPA 15 mg and 30 mg, respectively; non-melanoma skin cancer were 1.4 E/100 PY with UPA 30 mg, with no cases with UPA 15 mg or PBO. Venous thromboembolic events were low in the UPA groups with no cases reported in PBO (table 1).

Conclusion

Response rates were significantly greater with UPA 15 mg and 30 mg versus PBO across all endpoints. Generally, both UPA doses were well tolerated and have a favorable benefit-risk profile after 52 weeks’ maintenance. The safety of UPA will continue to be monitored.