Endoscopic Improvement Research Articles

Risankizumab Is Associated With Normalization of Biomarkers in Patients With Crohn's Disease: Results From the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Studies.

Normalization of high-sensitivity C-reactive protein [hs-CRP] and fecal calprotectin [FCP] are suggested Crohn's disease [CD] intermediate treatment targets. This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab. This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP [> 5mg/L] or FCP [> 250 µg/g] concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study. We assessed the proportion of patients achieving biomarker normalization, defined as hs-CRP ≤ 5mg/L and FCP ≤ 250 µg/g, and the association between achieving biomarker normalization and improved clinical and endoscopic outcomes. Among 748 patients with elevated baseline hs-CRP or FCP concentrations, higher proportions of patients treated with risankizumab vs placebo achieved normalization of hs-CRP [week 12: placebo, 17.5%; risankizumab 600mg, 48.5%; week 52: placebo, 29.5%; risankizumab 180mg, 45.2%; risankizumab 360mg, 40.8%] and FCP [week 12: placebo, 9.1%; risankizumab 600mg, 26.0%; week 52: placebo, 28.0%; risankizumab 180mg, 43.0%; risankizumab 360mg, 44.0%; nominal p < 0.05 vs placebo for all comparisons]. Achievement of both clinical or endoscopic outcomes and improvement of biomarker concentrations occurred at higher rates among patients treated with risankizumab vs placebo, regardless of prior exposure to biologic therapies. Risankizumab treatment led to sustained normalization of inflammatory biomarkers with improved clinical and endoscopic results.

Practice patterns for eosinophilic esophagitis vary widely among Canadian gastroenterologists: a nationwide survey

Abstract Introduction Eosinophilic esophagitis (EoE) is a chronic allergic, type 2, immune-mediated condition of the oesophagus, resulting in dysmotility and oesophageal stricturing. This study aims to identify practice variation among Canadian gastroenterologists treating adults with EoE. Methods A cross-sectional, web-based survey was distributed to Canadian gastroenterologists through the Canadian Association of Gastroenterology and administrations of Canadian universities. Results Seventy gastroenterologists completed the survey, with 59% working in academic practice or research. Overall, 90% of gastroenterologists require histological evidence of EoE to establish a diagnosis of EoE, while 50% require clinical symptoms of oesophageal dysfunction; 39% of gastroenterologists take less than 5 biopsies when assessing for EoE, with variability in biopsy location. Only 51% of respondents took biopsies in every case presenting with acute food bolus. Proton pump inhibitors were the initial therapy of 70% of gastroenterologists, with 11% using topical steroids. The preferred dietary approach was the 6-food elimination diet in 36%, followed by the 2-food elimination diet in 26%. Overall, 27% of participants did not use histologic improvement and 63% did not use endoscopic improvement to evaluate treatment response. Use of EoE Endoscopic Reference Score (EREFS) is low, with 56% being either unaware of what EREFS is or never using it. Most respondents feel Canadian guidelines would be helpful in their practice. Conclusions Eosinophilic esophagitis practice patterns among Canadian gastroenterologists are variable and differ from consensus guidelines. The development of Canadian guidelines and continuing medical education content can be considered to improve the management of EoE in Canada.

Exploring Dual-Targeted Therapy in the Management of Moderate to Severe Inflammatory Bowel Disease: A Retrospective Study

Abstract Background Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extra-intestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center. Methods This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles. Results Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and post-dual-targeted therapy Mayo scores for UC (p = 0.002) and SES-CD scores for CD (p = 0.018). The median pre- and post-dual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3) respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20) respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/hr to 9 [range 0-116] mm/hr, p = 0.006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, p &amp;lt;0.001) , and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], p &amp;lt; 0.001). Non-obesity was associated with both more endoscopic improvement (p = 0.002) and clinical improvement (p = 0.007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported. Discussion Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD, and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.

Real-World Effectiveness and Safety of Carotegrast Methyl in Japanese Patients with Moderately Active Ulcerative Colitis

Introduction: Carotegrast methyl (CGM) is an oral, small-molecule α4-integrin antagonist, which became clinically available in Japan in May 2022. CGM is approved for remission induction treatment for moderately active ulcerative colitis (UC) with an inadequate response or intolerance to 5-aminosalicylates. Methods: We performed a single-center, retrospective, observational study of Japanese patients with moderately active UC to assess the real-world effectiveness and safety of CGM as remission induction treatment. Results: Of 14 patients, 71% (10/14) were women, and the median (range) age was 47 (20–68) years. Disease types were proctitis in 7% (1/14), left-sided colitis in 50% (7/14), and total colitis in 43% (6/14). With a median (range) treatment duration of 8 (2–26) weeks, the rate of endoscopic improvement (Mayo endoscopic subscore [MES] of 0 or 1) was 64% (9/14), and the rate of endoscopic remission (MES of 0) was 57% (8/14). After treatment with CGM, the median (range) MES decreased significantly from 3.0 (2–3) to 0.0 (0–3) (p = 0.008), the Mayo score decreased significantly from 7.0 (5–9) to 0.0 (0–9) (p = 0.006), and the clinical activity index decreased significantly from 6.0 (1–11) to 0.0 (0–9) (p = 0.015). Stool and diarrhea frequencies decreased significantly after initiating CGM, and the percentage of patients with bloody stool and abdominal pain tended to decrease. The cumulative relapse-free rate at week 26 among 9 patients who achieved endoscopic improvement with CGM was 77.8% (95% confidence interval, 36.5%–93.9%). No adverse drug reactions, including progressive multifocal leukoencephalopathy, were reported during the study period. Conclusion: This single-center, retrospective, observational study of 14 Japanese patients with UC showed that CGM was safe and effective as a remission induction treatment for moderately active UC with an inadequate response to 5-aminosalicylates in real-world settings.

Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

Cost-effectiveness and cost-utility of optimized mercaptopurine treatment versus placebo in ulcerative colitis patients: The randomized controlled OPTIC trial.

We assessed the cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment compared with placebo in ulcerative colitis (UC) patients failing 5-aminosalicylates. Data were gathered alongside the randomized controlled OPTIC trial (EudraCT: 2015-005260-41). The evaluation was performed from a health care and societal perspective as cost-effectiveness and cost-utility analyses with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. The main outcomes were the extra costs per additional patient who achieved clinical remission and endoscopic improvement at 52weeks (responders) and extra costs per quality-adjusted life-year (QALY) gained. In total, 59 patients were randomized to the intervention (n=29) and control (n=30) group. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.93) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.64) in favour of mercaptopurine from a societal perspective. The higher proportion of responders and a non-significant QALY difference of 0.0475 (-0.024-0.117) (P=0.184) favouring patients on mercaptopurine treatment resulted in €165 extra costs per additional responder and €1326 extra costs per QALY gained from a health care perspective. From a societal perspective, dominance over placebo was observed with cost savings of €1937 per additional responder and €15,621 per QALY gained. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000. TDM-based mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

Comparative Efficacy and Safety of Upadacitinib vs. Vedolizumab, Ustekinumab, and Tofacitinib After Induction and Maintenance for Ulcerative Colitis: Three Matching-Adjusted Indirect Comparisons.

Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited. Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30mg, VEDO 300mg intravenously every 8weeks (Q8W), UST 90mg SC Q8W, or oral TOFA 5mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator. The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15mg versus VEDO and TOFA (p<0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators. In patients with active UC, greater clinical efficacy, and similar safety after 1year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.

Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis

We performed an updated systematic review and network meta-analysis to inform the 2024 American Gastroenterological Association (AGA) Clinical Guidelines on the management of moderate-to-severe ulcerative colitis (UC). We searched multiple electronic databases through November 21, 2023, to identify randomized controlled trials in adults with moderate-to-severe UC, comparing different advanced therapies (tumor necrosis factor antagonists, vedolizumab, sphingosine-1-phosphate receptor modulators, interleukin 12/23 or selective interleukin 23 antagonists, and Janus kinase [JAK] inhibitors) against placebo or another active comparator. Our primary outcomes were induction and maintenance of clinical remission, and our secondary outcome was endoscopic improvement. We performed a network meta-analysis using a frequentist approach and applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence. After excluding JAK inhibitors as potential first-line treatment (in accordance with the United States Food and Drug Administration), low-certainty evidence supports clinically important benefit with infliximab, ozanimod, risankizumab, and guselkumab over adalimumab and mirikizumab for achieving remission with induction therapy in biologically naïve patients with moderate-to-severe UC, with risankizumab and ozanimod being ranked the highest for induction of clinical remission. With the inclusion of JAK inhibitors as first-line therapy, upadacitinib was more efficacious compared with all other medications except ozanimod and risankizumab, with low- to moderate-certainty evidence. In patients with prior biologic exposure, upadacitinib, tofacitinib, and ustekinumab were ranked highest for achieving remission. Using Grading of Recommendations, Assessment, Development and Evaluation to appraise quality of evidence, this updated network meta-analysis will be used to inform comparative efficacy and positioning of advanced therapies for the treatment of biologic-naïve and biologic-exposed patients with moderate-to-severe UC.

S1472 Efficacy of Risankizumab Maintenance Therapy by Clinical Remission and Endoscopic Improvement Status in Patients With Moderately to Severely Active Ulcerative Colitis: Post Hoc Analysis of the COMMAND Phase 3 Study

S1472 Efficacy of Risankizumab Maintenance Therapy by Clinical Remission and Endoscopic Improvement Status in Patients With Moderately to Severely Active Ulcerative Colitis: Post Hoc Analysis of the COMMAND Phase 3 Study

The intestinal mucin isoform landscape reveals region-specific biomarker panels for inflammatory bowel disease patient stratification.

Mucosal healing is considered as a key therapeutic endpoint in inflammatory bowel diseases (IBD) and comprises endoscopic improvement of inflammation without taking barrier healing into account. Mucins are critical components of the mucosal barrier function that give rise to structurally diverse isoforms. Unraveling disease-associated mucin isoforms that could act as an indication for barrier function would greatly enhance IBD management. We present the intestinal mucin RNA isoform landscape in IBD and control patients using a targeted mucin isoform sequencing approach on a discovery cohort (n = 106). Random Forest modeling (n = 1683 samples) with external validation (n = 130 samples) identified unique mucin RNA isoform panels that accurately stratified IBD patients in multiple subpopulations based on inflammation, IBD subtype (Crohn's disease (CD), ulcerative colitis (UC)), and anatomical location of the intestinal tract (i.e. ileum, proximal colon, distal colon, rectum). Particularly, the mucin RNA isoform panels obtained from the inflamed UC and CD distal colon showed high performance in distinguishing inflamed biopsies from their control counterparts (AUC of 93.3% and 91.1% in the training, 95.0% and 96.0% in the test, and 89.5% and 78.3% in the external validation datasets, respectively). Furthermore, the differentially expressed MUC4 (PB.1238.363), MUC5AC (PB.2811.15), MUC16 (ENST00000397910.8) and MUC1 (ENST00000462317.5, ENST00000620103.4) RNA isoforms frequently occurred throughout the different panels highlighting their role in IBD pathogenesis. We unveiled region-specific mucin RNA isoform panels capturing the heterogeneity of the IBD patient population and showing great potential to indicate barrier function in IBD patients.

Safety and Efficacy of Upadacitinib in Crohn's Disease: An Updated Systematic Review.

Crohn's disease (CD) is a chronic inflammatory bowel disease that significantly impacts patient quality of life. This systematic review evaluates the safety and efficacy of upadacitinib, a selective Janus kinase (JAK) inhibitor, in the treatment of CD. A comprehensive literature search was conducted across multiple databases, yielding seven studies published between 2020 and 2024, encompassing 1,481 patients. The review includes randomized controlled trials, post hoc analyses of phase 3 trials, and observational studies. Findings consistently demonstrate upadacitinib's superiority over placebo in inducing and maintaining clinical remission, achieving endoscopic response, and normalizing inflammatory markers. Notably, upadacitinib showed rapid symptom relief, with clinical remission observed as early as five to six days after treatment initiation. Efficacy was observed across various patient populations, including those with prior biologic failure. Long-term studies indicated sustained clinical and endoscopic improvements, with remission rates maintained for up to 30 months. Upadacitinib also demonstrated effectiveness in real-world, treatment-refractory cohorts. Safety profiles were generally consistent with those of other JAK inhibitors. Common adverse events included infections, particularly herpes zoster, and laboratory abnormalities such as neutropenia and elevated creatine kinase. Serious adverse events were infrequent, although careful monitoring is warranted. This review suggests that upadacitinib is a promising treatment option for moderate to severe CD, offering rapid and sustained efficacy with an acceptable safety profile.

Outcomes of patients with prior biologic intolerance are better than those with biologic failure in clinical trials of inflammatory bowel disease

Abstract Background and Aims Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance. This study aimed to assess clinical outcomes in IBD patients with prior biologic failure versus intolerance treated with ustekinumab or vedolizumab. Methods A post-hoc analysis of ulcerative colitis (UC) and Crohn’s disease (CD) clinical trials for ustekinumab (UNITI, UNIFI) and vedolizumab (GEMINI-1, GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic-failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed. Results 1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs. 38.8%, aOR 1.87 [95% CI 0.93-3.73]), clinical remission (25.0% vs. 11.0%, aOR 2.84 [95% CI 1.47-5.49]), and endoscopic improvement (40.6% vs. 24.8%, aOR 2.76 [95% CI 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic-intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI 0.88-2.49). Conclusion Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure versus intolerance to mitigate potential bias.

Efficacy and safety of the S1PR modulator etrasimod in the treatment of moderately to severely active ulcerative colitis during the induction phase: a systematic review and meta-analysis of randomized controlled trials.

The study aims to assess the efficacy and safety of the recently approved S1PR modulator etrasimod in adults with ulcerative colitis during the induction phase through meta-analysis. A systemic search was performed for randomized controlled trials evaluating the efficacy and safety of the S1PR modulator etrasimod using electronic databases PubMed, Embase, the Cochrane Library, Clinical Trials, and the International Clinical Trials Registry Platform. Three studies with 943 patients met the inclusion criteria and were included in this analysis. The study's primary endpoint was the proportion of patients who achieved clinical remission at week 12. Key secondary endpoints included the proportion of patients with clinical response, endoscopic improvement, and histologic remission. The incidence of adverse effects (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of etrasimod. This study revealed that etrasimod is superior to placebo at the primary endpoint clinical remission (OR = 3.09, 95% CI: 2.04-4.69), as well as at the secondary endpoints clinical response (OR = 2.56, 95% CI: 1.91-3.43), endoscopic improvement (OR = 2.15, 95% CI: 1.51-3.05), and histologic remission (OR = 3.39, 95% CI: 2.03-5.68). The proportion of patients with TEAE (OR = 1.34, 95% CI: 1.01-1.78) and SAE (OR = 0.77, 95% CI: 0.41-1.43) was similar between the etrasimod and placebo groups. Patients receiving etrasimod had slightly higher odds of experiencing headache (OR = 2.07, 95% CI: 1.01-4.23), and nausea (OR = 1.84, 95% CI: 0.72-4.72). The incidences of upper respiratory tract infection (OR = 0.79, 95% CI: 0.27-2.32), nasopharyngitis (OR = 0.40, 95% CI: 0.15-1.07), and urinary tract infection (OR = 1.82, 95% CI: 0.59-5.60) were generally lower in the etrasimod groups and no treatment-related serious infections were reported. This study demonstrates that etrasimod is effective in treating moderately to severely active ulcerative colitis with a favorable benefit-risk profile at week 12. Etrasimod shows promise as a potential first-line oral therapy for individuals suffering from this disease. Additional RCTs with larger sample sizes and longer observation periods are needed to confirm the sustained efficacy of etrasimod beyond the initial phase.

Safety and efficacy of S1P receptor modulators for the induction and maintenance phases in inflammatory bowel disease: A systematic review and meta-analysis of randomized controlled trials.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that significantly affects quality of life. Conventional treatments have had limited success. this study evaluates the safety and efficacy of Sphingosine 1-phosphate receptor modulators (S1PrMs) as a potential treatment for IBD. We conducted a thorough search of published literature on PubMed, EMBASE, and Google Scholar from 2000 to 2023. The inclusion criteria were randomized controlled trials (RCTs) with a target population comprising of IBD patients receiving either S1PrMs or placebo and a comparison of the 2. The statistical analysis was conducted using RevMan (version 5.4). Forest plots presented the results as risk ratios (RR) with a 95% confidence interval. A total of 7 RCTs involving 2471 patients were included. The results were reported for both the induction and maintenance phases of treatment. in the induction phase, the intervention group proved to have a significantly higher incidence of histological remission (RR = 2.67; 95% CI [1.97, 3.60]; P < .00001), endoscopic improvement (RR = 2.06; 95% CI [1.66, 2.56]; P < .00001), clinical remission (RR = 2.23; 95% CI [1.43, 3.46]; P < .0004) and clinical response (RR = 1.37; 95% CI [1.01, 1.84]; P = .04) compared to the placebo group. Outcomes assessed in maintenance phase significantly favored the intervention group over placebo as well, histologic remission (RR = 2.39; 95% CI [1.83, 3.11]; P < .00001), endoscopic improvement (RR = 2.20; 95% CI [1.28, 3.77]; P = .004), clinical remission (RR = 3.03; 95% CI [1.84, 4.99]; P < .0001), and clinical response (RR = 1.74; 95% CI [1.25, 2.42]; P = .001). S1PrMs show promising potential for establishing histologic remission, endoscopic improvement, clinical remission, and corticosteroid-free clinical remission. With more studies and clinical trials, these modulators may become a reliable therapeutic choice for UC patients everywhere.

Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis

Background & aimsTreatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network-meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC. MethodsThe literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score [MES] ≤1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES = 0) and histological remission. A sub-analysis was performed based on the RCT design and previous exposure to biologic therapy. ResultsWe identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%) respectively. In maintenance of endoscopic improvement, upadacitinib ranked first (98.6%) followed by filgotinib 200 mg (79.2%). Risankizumab ranked first in the induction of histological remission (89.4%). Followed by guselkumab (88.3%). Upadacitinib ranked first (93.1%) in maintaining histological remission followed by guselkumab (89.5%). ConclusionUpadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective IL-23s as alternatives to other biologics.

Efficacy and Safety of Sphingosine 1-Phosphate Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy. Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo. Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

Mupirocin Ointment Effect on Polyposis Recurrence After Sinus Surgery.

Staphylococcus aureus is an identified pathogen involved in the recurrence of symptoms in patients with chronic rhinosinusitis with nasal polyps. We investigated the effectiveness of a topical ointment of mupirocin applied in the nasal vestibule in lessening symptom recurrence and improving the efficiency of functional endoscopic sinus surgery. Patients with chronic rhinosinusitis, nasal polyps, and a positive nostril culture for Staphylococcus aureus were included in a clinical trial. The right nostril was determined as the intervention group (applying mupirocin ointment) and the left as the control group (applying vitamin A ointment). Lund-Mackay radiological scores and Lund-Kennedy endoscopic scores were examined at the time of diagnosis and six months later. Among 60 patients with chronic rhinosinusitis with nasal polyps, 91.6% were positive for nostril Staphylococcus aureus. Comparing the average of the diagnostic radiological and endoscopic scores with the follow-up values in both groups indicated a significant improvement after surgery (P-value=0.001, 0.001). However, there was no significant difference in the radiological and endoscopic score improvements between the study and control groups (P-value > 0.56, 0.74). Nasal mupirocin administration following endoscopic sinus surgery cannot significantly prevent symptom recurrence in chronic rhinosinusitis with nasal polyps.

Long-term safety and efficacy of filgotinib for the treatment of moderately to severely active ulcerative colitis: Interim analysis from up to 4 years of follow-up in the SELECTION open-label long-term extension study.

Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis. The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535). In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health-related quality of life (HRQoL). We compared safety and efficacy between achievers and non-achievers of a multi-component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements. Data for completers (n = 250) and non-responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as-observed proportion of FIL200-treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non-responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid-free pMCS remission than non-achievers, up to LTE week 96. Filgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long-term benefit-risk profile. FIL200-treated CDC achievers had better long-term outcomes than non-achievers.

Model-Informed Assessment of Probability of Phase 3 Success for Ritlecitinib in Patients with Moderate-to-Severe Ulcerative Colitis.

Ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor, was evaluated in patients with ulcerative colitis (UC) in a phase 2b trial. Model-informed drug development strategies were applied to bridge observations from phase 2b to predictions for a proposed phase 3 study design to assess the probability of achieving the target efficacy outcome. A longitudinal exposure-response model of the time course of the 4 Mayo subscores (rectal bleeding, stool frequency, physician's global assessment, and endoscopic subscore) in patients with UC receiving placebo or ritlecitinib was developed using population modeling approaches and an item response theory framework. The quantitative relationships between the 4 Mayo subscores accommodated the prediction of composite endpoints such as total Mayo score and partial Mayo score (key endpoints from phase 2b), and modified clinical remission and endoscopic remission (proposed phase 3 endpoints). Clinical trial simulations using the final model assessed the probability of candidate ritlecitinib dosing regimens (including those tested in phase 2b and alternative) and phase 3 study designs for achieving target efficacy outcomes benchmarked against an approved treatment for moderate-to-severe UC. The probabilities of achieving target modified clinical remission and endoscopic improvement outcomes at both weeks 8 and 52 for ritlecitinib 100 mg once daily was 74.8%. Model-based assessment mitigated some of the risk associated with proceeding to pivotal phase 3 trials with dosing regimens of which there was limited clinical experience.

Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study.

Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3years. A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.