Two phase 3 induction trials (U-ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]) have demonstrated efficacy of upadacitinib over placebo in patients with moderately to severely active UC. Especially in patients who have had an inadequate response (IR) to a biologic or conventional therapy, a targeted induction therapy is needed.
Therefore, the study presented by Prof. Séverine Vermeire (University Hospital Leuven, Belgium) aimed to assess the efficacy of upadacitinib (45 mg once daily) in patients who showed previous IR to biologics or conventional therapies1. Primary endpoint was the clinical remission per Adapted Mayo Score at week 8 (Stool Frequency Score ≤1 and not greater than baseline, Rectal Bleeding Score=0, Mayo Endoscopic Subscore ≤1).
Upadacitinib was superior to placebo in both biologic-IR patients and non-biologic-IR patients in both the U-ACHIEVE trial and the U-ACCOMPLISH trial. In the biologic-IR patients of the U-ACHIEVE trial, clinical remission was achieved in 18% of the upadacitinib patients (n=168) versus 0% of the placebo patients (n=78). Of the non-biologic-IR patients in this trial, 35% of the upadacitinib receivers (n=151) reached clinical remission compared with 9.2% of the placebo patients (n=76).
The U-ACCOMPLISH trial showed similar rates. Moreover, secondary endpoints demonstrated a superior efficacy of upadacitinib over placebo as well. No new safety issues emerged in this subgroup analysis.