Loftus, Edward V.

Abstract Background Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive. Methods The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES. Results The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman’s r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820). Conclusions This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

ABSTRACTBackgroundInflammatory bowel disease (IBD) in adults with primary sclerosing cholangitis (PSC) is characterized by pancolonic involvement, a high frequency of rectal sparing, and an increased risk of pouchitis and colorectal neoplasia. The clinical features of IBD in pediatric patients with PSC have not been well described. The aim of this study was to characterize the frequency, clinical features, and natural history of IBD in pediatric patients diagnosed with PSC.MethodsA retrospective chart review was performed for all patients 18 years of age or younger diagnosed with PSC seen at the Mayo Clinic between 1975 and 1999. Endoscopic and histologic features and surgical and postsurgical outcomes were recorded.ResultsFifty‐two children with PSC were identified. Forty‐three patients (84%) were also diagnosed with IBD. In 36 of 43 cases, there was a sufficient diagnostic evaluation to allow a detailed review. Thirty‐two of 36 patients (89%) had ulcerative colitis and 4 of 36 patients (11%) had Crohn’s disease. In 4 of 36 patients (11%), IBD was asymptomatic. Although the most frequent endoscopic presentation of IBD was universal colitis, endoscopic rectal sparing was frequently noted (27% of colonoscopic studies). Of the four patients diagnosed with Crohn disease, in none did perianal, fistulizing, or stricturing disease develop. Proctocolectomy was performed in six patients (17%); three operations were performed for dysplasia. Pouchitis complicated four of the five ileal pouch–anal anastomoses procedures.ConclusionsAmong pediatric patients (1) PSC without IBD is uncommon; (2) asymptomatic IBD may be associated with PSC; (3) because the time to dysplasia may be accelerated, once the diagnosis of IBD is made in the setting of PSC, heightened endoscopic surveillance may be indicated; (4) pouchitis occurs frequently in these patients.

SummaryBackgroundUpadacitinib is an oral, selective Janus kinase inhibitor.AimTo assess the efficacy and safety of upadacitinib in patients with moderate‐to‐severe ulcerative colitis following 16‐week extended induction therapy, and 52‐week maintenance therapy in patients achieving clinical response after 16‐week extended induction therapyMethodsPatients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re‐randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52‐week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout.ResultsOverall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib.ConclusionsPatients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy.Clinical trial registration: NCT02819635; NCT03653026

Abstract Background and Aims This post hoc analysis assessed the efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis stratified by corticosteroid use from the ulcerative colitis Phase 3 clinical trial programme. Methods Patients were randomised [1:2] to 8 weeks’ placebo or upadacitinib 45 mg once daily; Week 8 responders were re-randomised [1:1:1] to 52 weeks’ placebo or upadacitinib 15 or 30 mg daily. Corticosteroid dose was kept stable during induction but tapered according to a protocol-defined schedule [or investigator discretion] during maintenance Weeks 0–8. Efficacy outcomes and exposure-adjusted, treatment-emergent adverse event [TEAE] rates were assessed for induction and maintenance stratified by corticosteroid use at induction baseline. Results Overall, 377/988 [38%] patients were receiving corticosteroids at induction baseline [placebo, n = 133; upadacitinib 45 mg, n = 244] and 252 [37%] of the 681 clinical responders who entered maintenance were on corticosteroids at induction baseline [n = 84 for each treatment]. Similar proportions of patients receiving upadacitinib achieved clinical remission per Adapted Mayo Score with and without baseline corticosteroids at Weeks 8 and 52. The total proportion of patients re-initiating corticosteroids was higher with placebo [24/84;29%] vs upadacitinib 15 mg [16/81; 20%)] and 30 mg [11/81; 14%]. During induction, patients receiving corticosteroids at baseline had higher rates of TEAEs, serious TEAEs, and serious infections vs those not receiving corticosteroids; however, TEAE rates were similar during maintenance after corticosteroid withdrawal. Conclusions Upadacitinib is an effective steroid-sparing treatment in patients with moderately to severely active ulcerative colitis. Clinicaltrials.gov identifiers: NCT02819635; NCT03653026