Upadacitinib improves symptoms of ulcerative colitis as early as day one of initiation

A new study published in the Journal of Clinical Gastroenterology and Hepatology suggests that from day one, upadacitinib 45 mg once daily (QD) quickly reduced ulcerative colitis (UC) symptoms.

Upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, was tested for its effectiveness on the early symptomatic relief of ulcerative colitis. The earliest time point of efficacy onset was determined using post hoc analyses on pooled data from the two replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH.

The daily improvement in UC symptoms was assessed using diary entry data from the first dosage of placebo or upadacitinib 45 mg QD for 14 days (stool frequency, abdominal pain, rectal bleeding, and bowel urgency). At week 2, alterations in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP), as well as quality of life (QoL), were evaluated. These assessments were made at weeks 2 and 8. 

The key findings of this study were:

988 individuals (328 placebo, 660 upadacitinib) were examined in total. 

Between days 1 and 3, patients using upadacitinib saw substantial reductions in all UC symptoms compared to placebo, which persisted until day 14. 

75.7% and 48.2% of patients, respectively, exhibited a >50% decrease in hs-CRP and FCP levels from baseline (P .001 vs placebo). 

Significant improvements in QoL were seen at weeks 2 and 8, as well as increased rates of clinical remission/response per Partial Mayo score starting at week 2 (26.9%/59.4% upadacitinib 45 mg QD vs. 4.3%/22.3% placebo, P .001). 

Clinical remission/response at week 8 was significantly correlated with early improvements in stool frequency and bowel urgency by day 3, as well as decreases in hs-CRP and FCP by week 2.

Reference: 

Loftus, E. V., Jr., Colombel, J.-F., Takeuchi, K., Gao, X., Panaccione, R., Danese, S., Dubinsky, M., Schreiber, S., Ilo, D., Finney-Hayward, T., Zhou, W., Phillips, C., Gonzalez, Y. S., Shu, L., Yao, X., Zhou, Q., & Vermeire, S. (2022). Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. In Clinical Gastroenterology and Hepatology. Elsevier BV. https://doi.org/10.1016/j.cgh.2022.11.029