Comparative Effectiveness of Upadacitinib vs Corticosteroids as First-Line Therapy for Acute Severe Ulcerative Colitis（UPFRONT）

Keywords

• acute severe ulcerative colitis
• Upadacitinib
• Corticosteroids
• First-Line Therapy
• Randomized Controlled Trial

Study arms

• Experimental
  Upadacitinib group

  Upadacitinib extended-release tablets 45 mg once daily for 8 weeks, then adjusted to 30 mg once daily.

  Drug: Upadacitinib

• Active comparator
  Corticosteroid group

  Methylprednisolone for injection 60 mg/day. If clinical response is achieved, switch to oral prednisone acetate tablets after 5 days (calculated at 0.75 mg/kg/day), followed by a weekly prednisone taper of 5 mg. When the dose is reduced to 20 mg, taper by 2.5 mg weekly until discontinued, with mesalazine 4 g/day as maintenance therapy.

  Drug: Corticosteroid

Interventions

• DrugUpadacitinib

  Safety and efficacy of the drug

• DrugCorticosteroid

  Safety and efficacy of the drug

Primary outcomes

1. Primary Outcome Measure

   clinical response by day 7 (defined as a reduction in Lichtiger score to \<10 points with a decrease of ≥3 points from baseline improvement in rectal bleeding, and decreased stool frequency to ≤4 per day).

   Time frame: The primary outcome was assessed by the investigator between days 3 and 7, with patients recorded as clinical responders if they had the primary outcome on any day in this assessment window.

Secondary outcomes

1. clinical response by day 14

   Defined as mayo score decrease of ≥30% and ≥3 points from baseline, accompanied by a decrease in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1.

   Time frame: day 14

2. clinical remission by day 28, day 42, and day 90

   Total Mayo score ≤2 points and no individual subscore \>1 point.

   Time frame: day 28, day 42, and day 90

3. Endoscopic response by day 90

   A decrease in MES score of ≥1 point, or a decrease of ≥50% from baseline.

   Time frame: day 90

4. Endoscopic remission by day 90

   MES score ≤1

   Time frame: day 90

5. Endoscopic+clinical response

   Partial Mayo score ≤1 and MES ≤1

   Time frame: day 90

6. Clinical +FcP remission

   Partial Mayo score ≤1 and FcP≤250mg/kg

   Time frame: day 90

7. Clinical +CRP remission

   Partial Mayo score ≤1 and CRP≤5mg/L

   Time frame: day 90

8. Histologic remission

   typically defined as the absence of signs of neutrophilic infiltration. The specific criterion is a score below 2B.0, i.e., no increased neutrophils in the lamina propria.

   Time frame: day 90

9. Histologic improvement

   when assessing treatment efficacy, a score ≤ 3.1 (intraepithelial neutrophilic infiltration involving \< 50% of crypts) is used as the threshold for histologic improvement.

   Time frame: day 90

10. Adverse Reactions

    Adverse Reactions

    Time frame: day 90

11. IBDQ and fatigue questionnaire scores

    IBDQ and fatigue questionnaire scores

    Time frame: day 0 and day 90

Publications

• D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001 May;120(6):1323-9. doi: 10.1053/gast.2001.23983. PubMed 11313301 ↗
• Choy MC, Li Wai Suen CFD, Con D, Boyd K, Pena R, Burrell K, Rosella O, Proud D, Brouwer R, Gorelik A, Liew D, Connell WR, Wright EK, Taylor KM, Pudipeddi A, Sawers M, Christensen B, Ng W, Begun J, Radford-Smith G, Garg M, Martin N, van Langenberg DR, Ding NS, Beswick L, Leong RW, Sparrow MP, De Cruz P. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 Nov;9(11):981-996. doi: 10.1016/S2468-1253(24)00200-0. Epub 2024 Sep 2. PubMed 39236736 ↗

Individual participant data

Plan to share: No