Aldiabat, Mohammad

Abstract Background Upadacitinib (UPA) is an oral selective Janus kinase inhibitor approved for the management of moderate-to-severe Crohn’s disease (CD). One in ten CD patients may need a permanent ostomy (colostomy or ileostomy) during their disease course, and this may impact the efficacy of UPA, given its extended-release formulation. However, there is no data available in this population since patients with an ostomy are excluded from registrational CD trials. This study addresses this gap by comparing the real-world clinical effectiveness of UPA in CD patients with and without ostomy. Methods This retrospective cohort study analyzed data from the TriNetX US Collaborative Network of sixty-eight tertiary institutions, to examine adult (≥18 years) CD patients treated with UPA from May 19th, 2023 (FDA approval date) to October 31st, 2024. Patients were categorized based on presence or absence of an ostomy during the previous 5 years, after exclusion of patients with rheumatologic disease indications for UPA usage. A 1:1 propensity score matching (PSM) was performed to balance cohorts on demographics, baseline comorbidities, and CD severity indicators (CD phenotype, extraintestinal manifestations, concurrent corticosteroid and other biologics usage, hemoglobin, and body weight). Cox proportional hazards model estimated hazard ratios (HRs) in matched cohorts for clinical effectiveness as a composite outcome (corticosteroid use, hospitalizations, emergency room visits) and secondary individual outcomes, at one year post-treatment, with a significance threshold set at p < 0.05. Results The study sample of CD patients on UPA included 170 with and 1,428 without a prior ostomy. There were 144 patients in each cohort after PSM. Baseline characteristics of the cohorts are shown in Figure 1. After PSM (Figure 2), there were no significant differences between patients with CD on UPA, with and without prior ostomy, for composite outcomes (HR 0.93, p = 0.64), corticosteroid use (HR 0.78, p = 0.18), hospitalizations (HR 1.13, p = 0.64), or emergency room visits (HR 0.99, p = 0.97). Additionally, no significant differences were observed in opioid use (HR 0.95, p = 0.76), switch to another advanced therapy (HR 1.62, p = 0.06), or elevated biomarkers, including CRP (>10 mg/L, HR 1.00, p = 0.99) and fecal calprotectin (>150 µg/g, HR 0.85, p = 0.63) at the 1-year follow-up. Conclusion In CD patients, UPA demonstrated similar effectiveness for clinical outcomes of corticosteroid use, hospitalizations, emergency room visits and other secondary outcomes, regardless of their ostomy status.

Abstract Background The SEQUENCE trial, in bio-exposed Crohn's disease (CD) patients, demonstrated non-inferiority for clinical remission at 24 weeks and superiority for endoscopic remission at week 48 for risankizumab (RZB) compared to ustekinumab (UST). However, this comparison has not been adequately explored in bio-naive CD patients. Our study aimed to compare the clinical effectiveness among bio-naive CD patients treated with RZB vs. UST in a real-world setting, using data from a US-based multicenter cohort. Methods This retrospective cohort study utilized data from the TriNetX US Collaborative Network, comprising sixty-eight tertiary institutions, to examine adult (≥18 years) bio-naive CD patients initiated on RZB or UST from June 17th, 2022 (FDA approval date) to October 31st, 2024. Patients with prior advanced therapy usage and those with approved rheumatologic disease indications for RZB/UST were excluded. A 1:1 propensity score matching (PSM) analysis was conducted to balance cohorts on demographics, baseline comorbidities, and indicators of CD severity, including CD phenotype, extraintestinal manifestations, concurrent corticosteroid use, hemoglobin, and body weight. Cox proportional hazards models estimated hazard ratios (HRs) in matched cohorts for one-year post-treatment composite outcomes (need for corticosteroids, hospitalizations, emergency room visits, surgeries) with a priori significance threshold of p < 0.05. Results The study sample included 1,630 bio-naive CD patients treated with RZB and 3,105 with UST. Among patients on UST, 658 (21%) were dosed every four to six weeks, after the first dose. Baseline characteristics of the PSM RZB and UST cohorts are shown in Table 1 with 1,568 patients in each cohort. After PSM (Figure 1), there were no significant differences in composite outcome (HR 1.077, p = 0.170), corticosteroid use (HR 1.099, p = 0.110), CD-related surgery (HR 1.231, p = 0.284), hospitalization (HR 0.947, p = 0.615) or ER visits (HR 1.041, p = 0.687). Additionally, no significant differences were observed in opioid use (HR 1.062, p = 0.366), switch to different advanced therapy (HR 1.097, p = 0.468) or elevated disease biomarkers, including CRP (>10mg/l, HR 1.186 p = 0.101) or fecal calprotectin (>150 µg/g; HR 1.109, p = 0.407) at 1-year follow-up. Conclusion In this real-world experience allowing for drug optimization, no difference was observed in bio naïve patients between UST and RZB as far as clinical remission and progression of CD.