Improvement in patient-reported outcomes with upadacitinib in patients with moderately to severely active Crohn's disease: 52-week data from the CELEST study

INTRODUCTION: Upadacitinib (UPA), an oral selective JAK1 inhibitor was associated with clinical and endoscopic efficacy over 52 weeks in patients with moderate to severe refractory Crohn's disease. This is the first study assessing the long‐term effects of a JAK inhibitor (UPA) on patient‐reported outcomes (PROs) in Crohn's disease. AIMS AND METHODS: The 52‐week data from the phase 2, randomised, doubleblind CELEST study (M13‐740; NCT02365649) were analysed for long‐term effects of 4 UPA regimens on PROs. All patients who completed the 16‐week induction period were re‐randomised 1:1:1 into an Extension Phase to receive UPA 3 mg twice daily (BID), 12 mg BID or 24 mg daily (QD) for 36 weeks. The 24 mg QD arm was later stopped and a 6 mg BID arm was initiated to evaluate an intermediate maintenance dose. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQol (EQ‐5D) and Work Productivity and Activity Impairment (WPAI) PROs at baseline, week 16, and week 52. Outcomes at week 52 for patients who received UPA induction therapy and achieved clinical response at week 16 were assessed. Percentages of patients who achieved IBDQ response (defined as minimum clinically important differences (MCID) ≥16‐point increase in IBDQ score from baseline) and who achieved IBDQ remission (IBDQ score ≥170) at week 52 were determined using non‐responder imputation (NRI). Changes from baseline to week 52 were calculated using observed cases and analysis of covariance for IBDQ score, EQ‐5D visual analogue score (VAS) and WPAI. RESULTS: Among 220 patients enrolled in CELEST, 180 were re‐randomized into the Extension Phase. Of these, 153 patients received UPA induction therapy, of whom 94 achieved clinical response at week 16. Among week‐16 clinical responders, a greater proportion of patients in the BID dose groups attained IBDQ response (43.8%‐78.6%) and achieved IBDQ remission (43.8%‐50.0%) at week 52 than those in the 24mg QD dose group (Table). Dose‐related improvements in mean IBDQ scores (range 43‐71) and EQ‐5D VAS (range 18‐36) were observed in the 3mg, 6mg and 12mg BID dose groups at week 52. At week 52, improvements in WPAI including reduction of activity impairment (26‐42%) and work impairment (23‐38%) were numerically greater for the BID dose groups. CONCLUSION: Maintenance treatment with UPA among week‐16 clinical responders resulted in improved quality of life based on IBDQ, EQ‐5D and work productivity over 52 weeks. Numerically greater improvements were reported in the patients who received 12 mg BID.