The present study evaluated the efficacy of once daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). It performed the Post hoc analyses on pooled data to determine the earliest timepoint of efficacy onset.

The study analyzed the diary entry data for 14 days from the first dose of placebo or upadacitinib 45 mg QD for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). It assessed the alterations in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), fecal calprotectin (FCP) at week 2, and quality of life (QoL) at weeks 2 and 8. Regression analysis was employed to determine the association between alterations in UC symptoms and the probability of achieving clinical remission/response per Adapted Mayo score at week 8.

The study observed-

• Inclusion of 988 patients (n=328 placebo, n=660 upadacitinib). 
• Significant improvements in patients treated with upadacitinib vs. placebo in all UC symptoms between days 1 and 3, which remained till day 14. 
• A >50% reduction from baseline in hs-CRP and FCP levels in 75.7% and 48.2% of patients, respectively. 
• Increased rates of clinical remission/response per Partial Mayo score from week two and significant improvements in QoL at weeks 2 and 8. 
• Early improvement in stool frequency and bowel urgency by day 3, and reductions in hs-CRP and FCP by week 2, showed significant association with clinical remission/response at week 8.

This study shows that Upadacitinib 45 mg QD can provide rapid relief of UC symptoms from day 1.

Loftus EV Jr, Colombel JF, Takeuchi K, Gao X, Panaccione R, Danese S, Dubinsky M, Schreiber S, Ilo D, Finney-Hayward T, Zhou W, Phillips C, Gonzalez YS, Shu L, Yao X, Zhou Q, Vermeire S. Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. Clin Gastroenterol Hepatol. 2022 Dec 1:S1542-3565(22)01109-0. doi: 10.1016/j.cgh.2022.11.029. Epub ahead of print. PMID: 36464141.