Mucosal Healing Rate Research Articles

Clinical efficacy and its influencing factors of vedolizumab in the treatment of ulcerative colitis

Objective: To analyze the clinical efficacy and its influencing factors of vedolizumab (VDZ) in the treatment of ulcerative colitis (UC). Methods: The patients with moderately-to-severely active UC, who underwent VDZ treatment at the Second Affiliated Hospital of Wenzhou Medical University from November 2020 to November 2023 were retrospectively included. Based on whether 5-aminosalicylic acid (5-ASA) was used in combination with VDZ treatment, the patients were divided into combination group (received combination therapy of VDZ and 5-ASA) and monotherapy group (received monotherapy of VDZ). The clinical response rate and biological remission rate were analyzed at week 14. The clinical remission rate and mucosal healing rate were analyzed at week 38. The differences in efficacy of VDZ between the two groups were compared at week 14 and week 38, respectively. Multivariate logistic regression model was applied to analyze the influencing factors of clinical remission rate and mucosal healing rate in UC patients. Results: A total of 137 patients were included, including 74 males and 63 females, aged 18-76 (44±14) years old; Seventy-six cases in combination group and 61 cases in monotherapy group. At week 14 of VDZ treatment, the clinical response rate and biological remission rate were 79.6% (109/137) and 80.5% (33/41), respectively. At week 38, the clinical remission rate and mucosal healing rate were 78.8% (108/137) and 47.9% (57/119), respectively. There was no significant difference in clinical response rate and biological remission rate between combination group and monotherapy group at week 14 (both P>0.05). The clinical remission rate [85.5% (65/76) vs 70.5% (43/61), P=0.032] and mucosal healing rate [56.5% (39/69) vs 36.0% (18/50), P=0.027] were higher in combination group than those in monotherapy group at week 38. Multivariate logistic regression analysis showed that the combination therapy of VDZ and 5-ASA (OR=2.48, 95%CI: 1.02-6.03) and the clinical response at week 14 (OR=5.05, 95%CI: 1.98-12.85) were influencing factors of clinical remission rate of UC patients at week 38. Moreover, the baseline serum albumin (Alb) level ≥42.5 g/L was the influencing factor for the mucosal healing rate of UC patients at week 38 (OR=4.60, 95%CI: 2.06-10.24). Conclusions: VDZ is effective in treating UC patients. Both the combination of 5-ASA and the clinical response at week 14 are the influencing factors of the clinical remission rate at week 38. In addition, the baseline serum Alb level ≥42.5 g/L is the influencing factor of the mucosal healing rate at week 38.

Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to identify the safety and effectiveness of tofacitinib in patients with UC in routine clinical settings in Korea.MethodsThis open-label, observational, prospective, post-marketing surveillance study was conducted at 22 hospitals in the Republic of Korea. Patients with moderate to severe active UC who received tofacitinib were included and followed up for up to 52 weeks. Tofacitinib was administered at a dosage of 10 mg twice daily for at least 8 weeks, followed by 5 or 10 mg twice daily at the investigator’s discretion based on clinical evaluation according to the approved Korean label. Safety including adverse events (AEs) and effectiveness including clinical remission, clinical response, and endoscopic mucosal healing were evaluated. Safety analysis set was defined as all patients registered for this study who received at least one dose of tofacitinib according to the approved Korean label and followed up for safety data. Effectiveness analysis set included patients in the safety analysis set who were evaluated for overall effectiveness assessment and excluded patients who had received tofacitinib less than 8 weeks.ResultsA total of 110 patients were enrolled, of whom 106 patients were included in the safety population. The median duration of treatment was 370 days and the treatment duration ranged from 16 to 684 days for the safety population. AEs occurred in 42 patients (39.6%). Serious AEs (SAEs) occurred in 7 patients (6.6%) and of them, there were 2 cases of serious infections. These serious infections were reported as Adverse Event of Special Interest (AESI) in this study and no other AESI were reported. There were no cases of death during the study period. Clinical remission rates were 40.0%, 46.7%, 57.6%, and 55.1% at 8, 16, 24, and 52 weeks, and clinical response rates were 77.8%, 87.9%, 56.6%, and 81.4% at each visit, respectively. Endoscopic mucosal healing rates were 58.7% at 16 weeks and 46.2% at 52 weeks.ConclusionTofacitinib was effective in Korean patients with moderate to severe active UC and the safety findings were consistent with the known safety profile of tofacitinib.SummaryThis study confirmed the safety and effectiveness of tofacitinib in Korean patients with moderate to severe active UC in routine clinical settings.Trial registrationThis study is registered in the ClinicalTrials.gov under the identifier NCT04071405, registered on 28 August 2019.

Real-world Clinical Effectiveness and Safety of Vedolizumab and Adalimumab in Biologic-naive Patients With Crohn's Disease: Results From the EVOLVE Study.

This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

Mucosal Healing Among Black and White Patients With Inflammatory Bowel Disease.

Crohn's disease and ulcerative colitis are characterized by chronic inflammation of the gastrointestinal tract. Mucosal healing (MH) is a therapeutic goal in patients with inflammatory bowel disease (IBD). Current data suggest that Black patients may experience worse clinical outcomes than White patients with IBD. This study assessed MH between Black and White patients with IBD. Retrospective analysis was performed on Black and White adults with IBD who were hospitalized for an active flare. The presence of MH was assessed at 6-18 months after hospitalization. IBD treatments received before and during hospitalization, within 6 months, and 6-18 months after discharge were recorded. C-reactive protein (CRP) levels were collected at hospitalization and 6-18 months after discharge; the difference was reported as delta CRP. One hundred nine patients were followed up after hospitalization. Of those 88 (80.7%) were White patients, and 21 (19.3%) were Black patients. White and Black patients received similar proportions of IBD treatment before ( P = 0.2) and during ( P = 0.6) hospitalization, within 6 months ( P = 0.1), and 6-18 months ( P = 0.1) after discharge. Black patients achieved numerically higher rates of MH (15/21 = 71.4% vs 53/88 = 60.2%, P = 0.3) and delta CRP ( P = 0.2) than White patients, however, not statistically significant. In patients admitted to the hospital with an IBD flare with similar treatment and care, there was a trend toward higher rates of MH in Black patients compared with White patients. These data suggest that MH is likely not the only factor that is associated with Black patients experiencing worse clinical outcomes when compared with White patients.

Changes in the clinical course and prognosis of ulcerative colitis in Chinese populations: a retrospective cohort study.

Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China. This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007-2011, cohort II: 2012-2016, cohort III: 2017-2021). Patients' clinical characteristics and natural history were analyzed retrospectively. Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P= 0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P< 0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P< 0.001) and immunosuppressants (14.1% vs. 13.4%, P= 0.016), and days of hospitalization (13 days vs. 9 days, P< 0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P< 0.001). The rate of mucosal healing increased over time. In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Effectiveness and safety of vedolizumab and infliximab in biologic-naïve patients with moderate-to-severe ulcerative colitis: A multicenter, retrospective cohort study.

We conducted this multicenter, retrospective cohort study aiming to evaluate the effectiveness and safety of vedolizumab (VDZ) and infliximab (IFX) in biologic-naïve patients with moderate-to-severe ulcerative colitis (UC). Biologic-naïve patients with moderate-to-severe UC who were treated with IFX or VDZ for at least 14 weeks at three tertiary hospitals in southwest China between January 2021 and January 2023 were retrospectively included. Efficacy of the biologics was evaluated based on the steroid-free clinical remission rate, clinical remission rate, and mucosal healing rate at Weeks 14 and 52. Adverse events related to biologic use were recorded. Altogether 122 biologic-naïve patients with moderate-to-severe UC were included. No marked differences in the steroid-free clinical remission rate and clinical remission rate were observed between the two groups at Week 14 or Week 52 (P > 0.05). The VDZ group exhibited a higher mucosal healing rate at Week 14 compared to the IFX group (33.3% vs 16.9%, P = 0.036), while that at Week 52 did not differ between the two groups (65.6% vs 47.1%, P = 0.098). There was no statistically significant difference in the rate of adverse events between the two groups (P = 0.071). VDZ and IFX showed comparable clinical efficacy and safety profiles and can be used as viable first-line therapeutic options for biologic-naïve patients with moderate-to-severe UC.

Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease.

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

P520 Preferences towards treatment attributes among patients with Crohn’s disease and ulcerative colitis in Argentina, Australia, Brazil, Saudi Arabia and Taiwan: a discrete choice experiment

Abstract Background Advanced therapies (ATs) with different mechanisms of action and routes of administration (RoA) are used for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), and patients (pts) play an increasing role in the decision-making process.Pts’ preferences for treatment attributes from 7 European countries have been reported previously; however, evidence from non-European countries is lacking. Methods Adult pts with CD or UC on treatment for ≥6 months from Argentina, Australia, Brazil, Saudi Arabia and Taiwan were enrolled in this cross-sectional, self-administered online survey (Oct 2022 to May 2023). Pts’ preferences for IBD treatment attributes are described. In a discrete choice experiment, the relative importance of treatment attributes was estimated using conditional logit models. Results Overall, 706 pts with CD and UC (n=353 each) completed the survey. Mean (standard deviation [SD]) ages (years [y]) were 36.8 (9.9) and 37.7 (10.2), 47.9% and 47.6% were female, and mean (SD) disease durations (y) were 4.5 (6.0) and 4.6 (6.7) for CD and UC, respectively; 58.1% (CD) and 56.1% (UC) were exposed to ATs. For pts with CD, the rate of long-term remission on maintenance therapy (MT) was the most important attribute for treatment choice (32.5%), followed by the rate of 1-y remission (25.7%), RoA (24.6%) and risk of serious adverse events (AEs, 11.5%) and mild AEs (5.8%). For pts with UC, the rate of corticosteroid-free remission after 1 y was the most important attribute (30.8%), followed by RoA (27.4%), rate of mucosal healing after 1 y (16.1%), long-term remission on MT (14.9%) and risk of serious AEs (10.0%) and mild AEs (0.8%). Country-specific results are shown in the Table. Compared with intravenous administration every 4–8 weeks, pts with CD preferred subcutaneous (SC) administration every 1–2 weeks (odds ratio [95% confidence interval]: 1.41 [1.27–1.56] P&amp;lt;0.001) or every 4–12 weeks (1.22 [1.08–1.39, P=0.002]), and pts with UC preferred taking a tablet (1.41 [1.25–1.59], P&amp;lt;0.001) or SC administration every 4–12 weeks (1.30 [1.14–1.48], P&amp;lt;0.001) or every 1–2 weeks (1.20 [1.07–1.35], P=0.002). Pts exposed to ATs ranked the importance of RoA lower than that of effectiveness compared with AT-naïve pts, and 49.3% of pts with CD and 50.5% with UC indicated that they wanted ATs to start earlier. Conclusion This study highlights the importance of treatment effectiveness, RoA and safety for pts with IBD. Personalised care is crucial given that preferences for treatment attributes may vary across countries and among pts. Patient–physician shared decision-making discussions regarding therapy choice and timing should happen throughout the treatment journey.

DOP15 Results of a pragmatic multicentred randomised controlled trial investigating the use of personalised golimumab dosing in Ulcerative Colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis)

Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) often leading to impaired quality of life in affected patients. Current treatment modalities include anti-tumour necrosis factor (anti-TNF) monoclonal antibodies including infliximab, adalimumab and golimumab (GLM). RCT show higher trough drug levels (DL) following induction are associated with enhanced rates of remission in maintenance. GOAL-ARC is a pragmatic RCT to examine if dose optimisation of GLM following induction in response to suboptimal DL or persistently raised faecal calprotectin (FCP) improves rates of patient continuous clinical response (pCCR) and reduces maintenance disease activity in UC Methods A pragmatic randomised, multi-centre two-arm investigator initiated trial (NCT0268772) . Population – Patients with moderate to severe UC requiring TNF inhibitor therapy. Intervention - one arm receiving GLM treatment as per SMPC and one arm with dose optimisation of GLM based on FCP and DL from week 6 according to a dedicated algorithm. Eligible patients were randomised in a 1:1 ratio to 1 of 2 treatment groups. Study Duration - 46 weeks. Primary end-point pCCR = absence of flare defined as no increase in modified partial Mayo (MPM) score of 2 points from week 14-46 (requiring treatment intervention). Secondary endpoints included rate of clinical response to induction (week 14), defined as a drop of MPM of 2 points or decrease of ≥30% from baseline and level of FCP and rate of mucosal healing (Mayo endoscopic subscore of 0/1) at Wk 46 Results 107 patients were enrolled (target enrolment n=135, study enrolment terminated early due to recruitment problems during and following C19 pandemic). 97 patients (median age 42) were randomised, with one patient subsequently excluded due to ineligibility. Of 96 evaluable patients, 46 were randomised to SMPC treatment and 50 were randomised to the intervention. Baseline characteristic were comparable. 28/46 (61%) achieved wk 14 clinical response with SMPC and 19/46 (41%) met the primary endpoint (pCCR wk 14-46). In the intervention arm 28/50 (56%) achieved wk 14 clinical response and 24/50 (48%) met the primary endpoint (pCCR wk 14-46). The difference between groups in the rates of pCCR was 6.7% (95% CI:-0.15,0.29) in favour of the intervention and was not statistically significant. No safety signal associated with the intervention was observed. Conclusion In a pragmatic RCT no significant increase in the rate of pCCR was observed with personalised dosing of GLM for treatment of moderate to severe UC. A numerical trend towards reduced loss of response during maintenance (20% with SMPC versus 8% with intervention) is observed with personalised dosing of GLM suggesting this strategy may be beneficial in some patients

Inflammatory mesenteric fat detected by Intestinal ultrasound is correlated with poor long-term clinical outcomes in patients with Crohn's disease

BackgroundData on the correlation between inflammatory mesenteric fat (i-fat), detected by intestinal ultrasound (IUS), and the prognosis of Crohn's disease (CD) remains limited. AimsTo investigate the impact of IUS-detected i-fat on long-term clinical outcomes. MethodsWe retrospectively enrolled 171 active CD patients who initiated infliximab. Clinical remission (CR), mucosal healing (MH) and transmural healing (TH) were assessed at week-14 and 1 year. ResultsBaseline i-fat was detected in 107 patients, while 64 without i-fat. At week-14 and 1 year, patients with i-fat showed lower rates of CR (61.7% vs. 87.5%; 62.3% vs. 86.7%), MH (20.6% vs. 46.9%; 38.6% vs. 65.0%) and TH (10.3% vs. 31.3%; 21.6% vs. 51.7%), compared to those without (all p<0.01). Multivariable analysis revealed that baseline i-fat was a negative predictor for CR (OR=0.212) and MH (OR=0.425) at week-14, and CR (OR=0.340) and TH (OR=0.364) at 1 year (all p<0.05). At week-14, 56 patients with baseline i-fat recovered to without i-fat. Patients with i-fat recovery had higher rates of CR (86.8% vs. 23.1%), MH (58.5% vs. 7.7%) and TH (34.0% vs. 2.6%) at 1 year than those with i-fat at week-14 (all p<0.001). ConclusionIUS-detected i-fat correlated poor long-term clinical outcomes in CD with infliximab.

The Efficacy of Combination Therapy with Ustekinumab and Budesonide for Crohn’s Disease: A Randomized Controlled Trial

Introduction: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn’s disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. Methods: In this phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn’s disease with a Crohn’s disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. Results: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and <450). There was no difference between combination therapy and ustekinumab monotherapy in terms of clinical remission rates (50.0% vs. 30.0%, p = 0.39 at 8 weeks and 37.5% vs. 20.0%, p = 0.41) and mucosal healing rates (75.0% vs. 90.0%, p = 0.40 and 37.5% vs. 60.0%, p = 0.34 at 8 and 32 weeks, respectively). The most common adverse event was an exacerbation of Crohn’s. There were no differences in safety profiles between the two groups. Conclusions: Our study showed no difference between ustekinumab monotherapy and ustekinumab and budesonide combination therapy in terms of the induction and maintenance of remission (trial registration number: jRCTs021200013).

Higher Adalimumab Trough Levels Are Associated with Histologic Remission and Mucosal Healing in Inflammatory Bowel Disease.

(1) Many patients with inflammatory bowel disease (IBD) in endoscopic remission have persistent histologic activity, which is associated with worse outcomes. There are limited data on the association between adalimumab drug concentrations and histologic outcomes using validated histologic indices. We aimed to assess the relationship between adalimumab concentrations and the Robarts Histopathology Index (RHI). (2) Patients from a tertiary IBD center from 2013 to 2020 with serum adalimumab (ADA) trough concentrations measured during maintenance therapy (≥14 weeks) and a colonoscopy or flexible sigmoidoscopy with biopsies performed within 90 days of drug level were included. Blinded histologic scoring using the RHI was performed. Primary analysis assessed the relationship between adalimumab drug concentrations and histologic remission using receiver operating characteristic curve analysis. (3) In 36 patients (26 Crohn's Disease, 9 ulcerative colitis, 1 indeterminate), median adalimumab concentrations were higher (17.3 ug/mL, 12.2-24.0) in patients with histologic remission compared to those without (10.3 ug/mL, 6.8-13.9, p = 0.008). The optimal ADA concentration identified using the Youden threshold was ≥16.3 ug/mL (sensitivity 70%, specificity 90%). Patients with ADA ≥ 16.3 ug/mL had higher histologic remission rates (78%) compared to lower ADA concentrations (14%, p= 0.002), as well as higher mucosal healing rates (86%) compared to lower levels (12%, p = 0.001). Symptoms correlated weakly and non-significantly with both histologic (RHI) scores (r = 0.25, p = 0.2) and adalimumab concentrations (r = 0.05, p = 0.8). (4) The current study demonstrated that higher serum adalimumab concentrations (≥16.3 ug/mL) are needed for histologic remission and mucosal healing assessed using the RHI.

Combination of antimicrobials for non-specific isolated terminal ileal abnormalities - A randomized clinical trial.

Non-specific isolated terminal ileum abnormalities (NSITIA) namely erosions, ulcer and nodularity are frequent findings on ileal examination during colonoscopy. Their clinical significance and management are uncertain. A pilot randomized clinical trial comparing combination antimicrobial therapy (oralRifaximin 550mg twice daily for twoweeks; Albendazole 400mg orally as a single dose; Tinidazole 1 gm twice daily for threedays i.e. Group A) with symptomatic treatment (Group B) was performed in patients with NSITIA, which was diagnosed on the basis of colonoscopy and histopathology features. The primary outcome measure was mucosal healing on follow-up ileocolonoscopy at three months of randomization. Additionally, clinical, endoscopic and histological findings were noted at baseline and after a follow-up of threemonths. Total 60 patients with NSITIA were randomized. The most prevalent symptoms were abdominal discomfort (n = 37, 61.6%), diarrhea (n = 25, 41.6%) and constipation (n = 24, 40%). The incidence of ulcers, nodularity and erosions were (n = 18, 62.1%), (n = 8, 27.6%) and (n = 3, 10.34%) in group A and (n = 18, 58%), (n = 9, 29%), (n = 4, 13%) in group B, respectively. After a mean follow-up duration of 3.36 ± 0.27months, both groups showed comparable resolution in clinical symptoms (n = 24, 92.4% vs. n = 24, 88.8%, p = 0.954), ileocolonoscopic findings (n = 23, 88.5% vs. n = 22, 81.5%, p = 0.765) and histological characteristics (n = 20, 76.5% vs. n = 19, 70.4%, p = 0.806). The clinical, endoscopic and histopathological remission occurs in most patients with NSITIA. The use of antimicrobials including antibiotic, antiprotozoal and anthelminthic therapy did not have any impact on the rate of mucosal healing in these patients. Our study is a pilot study and has some limitations such as small sample size and lack of complete small bowel workup in all patients, which leaves a possibility of undetected ulcers proximal to the terminal ileum. This study has been registered in India's clinical trial registry under the registration number CTRI/2020/02/023459 ).

Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease.

Although increasing studies have reported that dose escalation can improve treatment response to ustekinumab in patients with Crohn's disease (CD), their strategies mainly focus on maintenance regimen. Evidence of ustekinumab dose escalation in induction regimen, particularly in severe CD, remains limited. This study evaluated the efficacy and safety of intravenous ustekinumab with 2 initial doses in patients with severely active CD. A retrospective observational study of 99 adult patients with severe CD treated with ustekinumab from 3 IBD centers included 48 patients with standard and 51 with optimized induction treatment. Clinical outcomes, inflammatory biomarkers including fecal calprotectin (FC) normalization, and endoscopic outcomes were evaluated at weeks 16 and 48. Adverse events and treatment decisions after initial induction were also collected. Compared with the standard group, 2 initial intravenous injections of ustekinumab achieved higher clinical response (92.2%, 47 of 51, P = .656), clinical remission (88.2%, 45 of 51, P = .221), endoscopic response (75.8%, 25 of 33, P = .125), and FC normalization (70.6%, 36 of 51, P = .138) at week 16. The mucosal healing rate at week 16 (63.6%, P = .022) was statistically higher in the optimization group. At week 48, patients with optimized treatment achieved higher clinical response (80.4%, 41 of 51, P = .003), clinical remission (70.6%, 36 of 51, P = .007), FC normalization (66.7%, 34 of 51, P = .031), endoscopic response (72.7%, 24 of 33, P = .006), and mucosal healing (57.6%, 19 of 33, P = .004). At the last follow-up, 82.4% of optimally treated patients adhered to continued treatment with ustekinumab (P < .001). Optimization of ustekinumab by 2 initial intravenous inductions is more effective than standard therapy for adult patients with severe CD.

A Treat-to-Target Strategy Guided by Pan-Enteric Evaluation in Children With Crohn's Disease Improves Outcomes at 2 Years.

It is uncertain whether a treat-to-target approach could be an effective strategy for improving outcomes in children with Crohn's disease (CD). Previously, we reported mucosal healing (MH) and deep remission rates throughout the intestinal tract by performing 3 pan-enteric capsule assessments and using a treat-to-target strategy over 52 weeks in children with CD. This report describes the outcomes of this approach at 104 weeks. Children with known CD who completed the 52-week protocol repeated pan-enteric capsule endoscopy (PCE) at 104 weeks. Results at weeks 52 and 104 were compared, and long-term outcomes between patients, with and without MH, were calculated using an intention-to-treat analysis of clinical relapse, need for steroids, treatment escalation, hospitalization, and surgery. Of the previous study cohort of 48 patients, 46 (96%) were available for this extension study (28 [61%] of 46 with MH and 18 [39%] of 46 without MH at 52 weeks). When evaluated at 104 weeks, MH was maintained in 93% of patients with MH at 52 weeks. In the intention-to-treat analysis, complete MH at 52 weeks was associated with reduced risk of steroid use (log-rank P < .0001), treatment escalation (log-rank P < .0001), hospitalization (log-rank P < .0001), and clinical relapse (log-rank P < .0001). When a PCE-based, treat-to-target strategy is employed, MH is sustainable (93%) over a 1-year period and is correlated with improved patient outcomes, including reduced need for steroids, treatment escalation, hospitalization, and clinical relapses at 104 weeks.ClinicalTrials.gov number: NCT03161886.

Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease.

Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings.

Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study.

Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.

Explore the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab in patients with ulcerative colitis

Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) μg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.

Effectiveness and safety of vedolizumab for ulcerative colitis: a single-center retrospective real-world study in China.

Introduction: The effectiveness and safety of vedolizumab (VDZ) against ulcerative colitis (UC) have been validated in several randomized controlled trials and real-world studies in Western countries. However, there are few studies on VDZ in Asia, and the follow-up period for these studies is generally short. Therefore, this study evaluates the long-term effectiveness and safety of VDZ in Chinese patients with UC. Methods: This retrospective study included patients with moderate to severe UC treated with VDZ between September 2019 and April 2022 at Sir Run Run Shaw Hospital, College of Medicine Zhejiang University. Clinical response and remission were assessed using the patient reported outcomes and the partial Mayo Score, and mucosal remission and healing were assessed using the Mayo Endoscopy Score. The primary endpoint was defined as clinical remission at week 14, and secondary endpoints included clinical response and steroid-free clinical remission at week 14, clinical response, clinical remission, and steroid-free clinical remission at week 52, and mucosal remission and healing at weeks 14 ± 8 and 52 ± 8. Results: Overall, 64 patients with moderate to severe UC were enrolled. The clinical response, clinical remission, and steroid-free clinical remission rates at week 14 were 73.4% (47/64), 65.6% (42/64), and 54.7% (35/64), respectively. Mucosal remission and healing rates at week 14 ± 8 were 64.7% (22/34) and 38.2% (13/34), respectively. A total of 48 patients were treated with VDZ for 52weeks. Based on intention-to-treat analysis, the clinical response, clinical remission, and steroid-free clinical remission rates at week 52 were 68.8% (44/64), 64.1% (41/64), and 64.1% (41/64), respectively. Mucosal remission and healing rates at week 52 ± 8 were 70.6% (12/17) and 35.3% (6/17), respectively. During the follow-up period, the most common adverse event was skin rash (6/64). No cases of acute infusion reactions, delayed allergic reactions, new hepatitis B infections, active tuberculosis, or malignant tumors were reported. Conclusion: In this single-center retrospective real-world study, the effectiveness of long-term use of VDZ for Chinese patients with UC was similar to the outcomes previously reported in other geographical regions and populations; no new safety signals were found compared with other registered studies.