Upadacitinib induces CD remission in patients with prior surgery

Treatment with upadacitinib (UPA) delivers clinical benefits to patients with prior Crohn’s disease (CD)-related surgeries, according to a study presented at AIBD 2023. Moreover, a maintenance dose of 30 mg once a day (QD) demonstrates greater efficacy.

“A higher maintenance dose may be more appropriate for patients with prior CD-related surgeries,” said the researchers, led by Edward Loftus, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, US. “Future prospective evaluation of this concept is merited.”

Loftus and his team conducted this post hoc analysis of U-EXCEL, U-EXCEED, and U-ENDURE phase III trials. Patients with one or more prior CD-related surgeries, including (but not limited to) bowel resection, ostomy, strictureplasty, abscess drainage (ie, abdominal, pelvic, perineal), fistulotomy, or seton placements, were evaluated.

The research team assessed clinical remission (CR) per CD Activity Index (CDAI, <150) and per stool frequency (SF)/abdominal pain score (APS; average daily very soft/liquid SF ≤2.8 and average daily APS ≤1.0, neither greater than baseline), endoscopic response (Simple Endoscopic Score for CD [SES-CD] decrease >50 percent from baseline or, for patients with baseline SES-CD=4, at least 2-point reduction from baseline), and endoscopic remission (SES-CD ≤4 and a ≥2-point decrease from baseline and no subscore >1 in any variable) at induction week 12 and maintenance week 52.

Patients from UPA and placebo groups showed similar demographic and baseline disease characteristics. Nearly half of participants (48.5 percent) had two or more prior CD-related surgical procedures, and majority of them (72.1 percent) had prior bowel resection.

In comparisons for UPA 45 mg versus placebo, patients with prior surgeries showed greater rates of CDAI CR (32.7 percent vs 20.1 percent; Δ, 12.5, 95 percent confidence interval [CI], 3.9‒21.2; p<0.01) and SF/APS CR (30.0 percent vs 12.1 percent; Δ, 10.2, 95 percent CI, 10.2‒25.4; p=0.0001), endoscopic response (23.7 percent vs 5.7 percent; p<0.0001), and endoscopic remission (9.8 percent vs 2.1 percent; Δ, 7.6, 95 percent CI, 3.4‒11.; p<0.01) at week 12. [AIBD 2023, abstract S7]

Response rates for UPA 15 and 30 mg at week 52 were higher relative to placebo: CDAI CR (UPA15: 22.6 percent; Δ, 11.8, 95 percent CI, ‒1.0 to 24.7; UPA30: 39.0 percent; Δ, 28.2, 95 percent CI, 13.7‒42.8; placebo: 10.8 percent; p<0.001) and SF/APS CR (UPA15: 21.0 percent; Δ, 11.7, 95 percent CI, ‒0.6 to 24.1; UPA30: 39.0 percent; Δ, 29.8, 95 percent CI, 15.5‒44.0; placebo: 9.2 percent; p=0.0001), endoscopic response (UPA15: 12.9 percent; Δ, 9.8, 95 percent CI, 0.5‒19.2; UPA30: 29.5 percent; Δ, 26.4, 95 percent CI, 13.9‒38.9; placebo: 3.1 percent; UPA15 vs placebo: p<0.05; UPA30 vs placebo: p=0.0001), and endoscopic remission (UPA15: 9.7 percent; Δ, 5.1, 95 percent CI, ‒3.9 to 14.0; UPA30: 20.5 percent; Δ, 15.8, 95 percent CI, 4.3‒27.4; placebo: 4.6 percent; p<0.001). Researchers noted a dose effect.

Additionally, “[p]atients with bowel resections, ostomy, or surgery or procedure for stricture (week 12: placebo, n=599; UPA45, n=218; week 52: placebo, n=543; UPA15, n=543; UPA30, n=544) had significant, albeit generally lower, response rate differences for UPA versus placebo, except CDAI CR, endoscopic response, and endoscopic remission,” the researchers said.

“No new safety signals were identified in patients with prior CD-related surgeries,” they added.