Parian, Alyssa M.

Abstract Background There is limited data on the clinical effectiveness of upadacitinib (UPA), an oral selective inhibitor of Janus kinase 1 (JAKi), in patients with perianal Crohn's disease (pCD). The objective of this study was to evaluate the real-world effectiveness of UPA in pCD. Methods This retrospective analysis utilized data on adults (>17 years) who initiated UPA at 45 mg/day for active pCD across 10 centers in the United States and Canada. Standardized data extraction and entry protocols were followed. The primary outcome was clinical response, defined as a ≥3-point reduction in Perianal Disease Activity Index (PDAI) between baseline and follow-up. Secondary outcomes included normalization of CRP (<5 mg/L) or hsCRP (<1 mg/L), clinical remission (PDAI ≤4), and rates of hospitalization, antibiotic use, corticosteroid initiation, and new pCD-related surgeries. Fistula healing on MRI pelvis fistula protocol was defined as an absence of T2-weighted hyperintensity and post-contrast enhancement on T1-weighted images. Predictive analyses used Cox proportional hazards models to evaluate baseline factors influencing time to PDAI remission, including BMI, CRP, albumin, PDAI, pCD disease duration, Montreal location and prior biologic exposure (<2 vs 2+). Results A total of 81 patients were treated with UPA for pCD (median age 35 years and 54.3% male). Most had ileocolonic disease (65.4%), with 54% presenting with complex fistulas. Of these, 92.6% had prior anti-TNF exposure, and 91 (88.9%) had prior exposure to 2+ biologics (Table 1). During a median follow-up of 4 months, clinical response (PDAI) was achieved in 17.3%. Improvement was observed in pain and restriction of activities (27.2%), restriction of sexual activity (13.6%), reduction in number of fistulas (11.1%), degree of induration (11.1%), and discharge (35.8%). Median CRP reduction was 21.05% [IQR: 0.00–74.53], and 21.0% achieved a ≥50% reduction in CRP. MRI healing was limited to 17.7% (6/34). Proctitis decreased from 23.5% at baseline to 7.4% at follow-up. During follow-up, hospitalizations occurred in 9.9%, 14.8% required antibiotics, 8.6% underwent examination under anesthesia in 8.6%, seton placement in 6.2%, and abscess drainage in 6.2%. Patients with ileocolonic disease showed the highest remission (54%) and response (15%) rates, while MRI healing was limited across all Montreal locations (7.4%). Lower baseline CRP (p < 0.05) and PDAI scores (p < 0.01) predicted shorter time to remission. Number of prior biologic exposures (p =0.2) and Montreal location (p = 0.7) were not predictive of time to PDAI remission (Figure 1). Conclusion UPA in a real-world cohort is effective in the management of treatment-refractory pCD. Randomized trials are needed to confirm these observations.

Abstract Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.