Endoscopic Healing Research Articles

Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos)

Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos)

Ulcerative colitis: Impact of early disease clearance on long‐term outcomes ‐ A multicenter cohort study

BackgroundClinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC.ObjectiveWe aimed to evaluate the impact of disease clearance on long‐term outcomes in UC patients.MethodsA multicenter retrospective cohort study was conducted at the Humanitas Research Hospital‐IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial‐Mayo score ≤2), endoscopic (endoscopic‐Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long‐time follow‐up (≥12 months), to compare the occurrence of negative outcomes.ResultsA total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC‐related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log‐rank p < 0.0001) and surgery (log‐rank p < 0.00095).ConclusionIn UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome.

Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease

Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. Among 81 patients (CD: n= 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Predictors of Placebo Induction Response and Remission in Ulcerative Colitis

Predictors of Placebo Induction Response and Remission in Ulcerative Colitis

Fecal calprotectin predicts endoscopic activity and mucosal healing of small bowel Crohn's disease evaluated by double-balloon endoscopy.

Fecal calprotectin (FC) levels can reflect the level of intestinal inflammation. Crohn's disease (CD), which affects the small bowel, has not been linked to FC levels. We determined if FC levels and endoscopic activity were related by performing double-balloon endoscopy (DBE). Herein, patients with small bowel CD diagnosed by DBE between January 2020 and January 2022 were prospectively observed. Feces and blood samples of patients were collected before performing DBE and checked for the levels of FC and serological biomarkers. The endoscopic activity and mucosal healing (MH) were evaluated using the partial simple endoscopic score (pSES-CD). In all 254 CD patients, FC levels were correlated with pSES-CD (r = 0.775, P < 0.001). Even in patients with isolated small bowel CD, FC levels were strongly correlated with pSES-CD (r = 0.753, P < 0.001). In all patients, FC as an endoscopic remission indicator was found to have an area under the curve (AUC) of 0.872, with a cut-off value of 156.09 µg/g. In patients with isolated small bowel CD, FC yielded a high AUC of 0.865 for predicting endoscopic remission, with a cut-off value of 211.48 µg/g, sensitivity of 73.95%, and specificity of 91.30%. FC was optimally cut-off at 76.99 µg/g to predict MH in accordance with the AUC of 0.877. Using DBE findings, FC was found to be significantly correlated with pSES-CD. Even in isolated small bowel CD, FC may be a more reliable marker of accurately predicting endoscopic remission and MH.

Racial Difference in Efficacy of Golimumab in Ulcerative Colitis.

Observational studies have described racial differences in inflammatory bowel disease (IBD) genetics, clinical manifestations, and outcomes. Whether race impacts response to biologics in IBD is unclear. We conducted a post hoc analysis of phase 2 and 3 randomized clinical trials in ulcerative colitis to evaluate the effect of race on response to golimumab. We analyzed pooled individual-level data from induction and maintenance trials of golimumab through the Yale Open Data Access Project. The primary outcome was clinical response. Secondary outcomes were clinical remission and endoscopic healing. Multivariable logistic regression was performed comparing White vs racial minority groups (Asian, Black, or other race), adjusting for potential confounders. There were 1006 participants in the induction (18% racial minority) and 783 participants in the maintenance (17% racial minority) trials. Compared with White participants, participants from racial minority groups had significantly lower clinical response (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.28-0.66), clinical remission (aOR, 0.41; 95% CI, 0.22-0.77), and endoscopic healing (aOR, 0.48; 95% CI, 0.31-0.74) at week 6. Participants from racial minority groups also had significantly lower clinical remission (aOR, 0.46; 95% CI, 0.28-0.74) and endoscopic healing (aOR, 0.63; 95% CI, 0.41-0.96) at week 30. There were no racial differences in placebo response rates. Ulcerative colitis participants from racial minority groups were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared with White participants in induction and maintenance trials. Further studies are needed to understand the impact of race on therapeutic response in IBD.

Usefulness of Examining Various Patient-Reported Outcomes in Predicting Endoscopic Mucosal Healing in Ulcerative Colitis

Background:Endoscopy remains the gold standard for evaluating mucosal healing in ulcerative colitis. However, given its invasiveness and high cost, it is not always possible to perform it as often. This study aimed to evaluate value of numerous patient-reported symptoms in the prediction of endoscopic mucosal healing.Methods:We prospectively conducted a cohort involving 143 patients with ulcerative colitis (men: 63.6%, median age: 40.0 years) in a tertiary teaching hospital between May 2017 and May 2020. Clinical remission was defined as resolution of rectal bleeding and normalization of stool frequency, set as basic patient-reported outcomes. The presence of additional 4 patient-reported outcomes (urgency, tenesmus, mucoid stool, and night defecation) were evaluated. Endoscopic activity was graded using the Ulcerative Colitis Endoscopic Index of Severity and endoscopic mucosal healing was defined as Ulcerative Colitis Endoscopic Index of Severity 0-1.Results:A total of 44 (30.77%) ulcerative colitis patients were categorized as achieving endoscopic mucosal healing. Across different patient-reported outcomes status in predicting endoscopic mucosal healing, clinical remission status inferred from basic patient-reported outcomes was superior to additional 4 patient-reported outcomes collectively (sensitivity/specificity: Ulcerative Colitis Endoscopic Index of Severity = 0/1, basic patient-reported outcomes 59.09%/75.76%, additional 4 patient-reported outcomes 70.45%/72.73%). Combination of basic and additional patient-reported outcomes revealed increased specificity of 83.84%. Multivariate analysis adjusted for age, sex, disease extent, and disease duration also revealed consistent results that patient-reported outcomes were independently associated to endoscopic mucosal healing (P < .001).Conclusion:Recognizing the presence of additional patient-reported outcomes may be useful in clinical practice as it is a simple and easy method that not only reflects patient’s quality of life but can also relatively better predict endoscopic mucosal healing status than basic patient-reported outcomes.

Transmural healing evaluated by magnetic resonance enterography in paediatric patients with Crohn's disease receiving maintenance treatment with biologics.

The optimal treatment goal in Crohn's disease (CD) is endoscopic healing (EH). However, transmural healing (TH) facilitated by the development and increasing performance of magnetic resonance enterography (MRE) is emerging as a potential treatment goal. To assess TH rates after 1year of treatment by MRE and its relationship with EH in paediatric patients with CD receiving anti-tumour necrosis factor (TNF) agents, and to investigate factors associated with TH after 1year of treatment. This multi-centre, prospective, observational study included Korean paediatric patients with luminal CD diagnosed at age < 19 years who were naïve to anti-TNF treatment. They simultaneously underwent ileocolonoscopy and MRE at baseline and after 1year of treatment with biologics. We included 116 patients. At 1year, EH and TH were achieved in 59.5% (69/116) and 38.8% (45/116) of the patients, respectively. Both EH and TH was observed in 35.3% (41/116), EH without TH in 24.1% (28/116), TH without EH in 3.4% (4/116), and neither EH nor TH in 37.1% (43/116). Moreover, 59.4% (41/69) of patients who achieved EH at 1year exhibited TH,and 91.1% (41/45) of patients who achieved TH exhibited EH. Baseline MaRIA score was associated with TH according to a multivariate analysis (OR 0.97, 95% CI 0.95-0.99, p=0.023). TH is a more stringent goal than EH. Regular follow-up evaluation of transmural status, and efforts to achieve TH, may alter the natural course of CD in the era of treat-to-target.

Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis.

Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.

Clinical, Endoscopic, and Radiological Effectiveness of Ustekinumab in Bio-naïve Versus Bio-experienced Patients With Crohn's Disease: Real-world Experience From a Large Canadian Center.

With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center. A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing. A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients. In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points.

Continuing Medical Education Questions: July 2022.

Article Title: Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease.

Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammation of the gastrointestinal tract with a highly heterogeneous presentation. It has a relapsing and remitting clinical course that necessitates lifelong monitoring and treatment. Although the availability of a variety of effective therapeutic options including immunomodulators and biologics (such as TNF, CAM inhibitors) has led to a paradigm shift in the treatment outcomes and clinical management of IBD patients, some patients still either fail to respond or lose their responsiveness to therapy over time. Therefore, according to the recent Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations, continuous disease monitoring from symptomatic relief to endoscopic healing along with short- and long-term therapeutic responses are critical for providing IBD patients with a tailored therapy algorithm. Moreover, considering the high unmet need for novel therapeutic approaches for IBD patients, various new modulators of cytokine signaling events (for example, JAK/TYK inhibitors), inhibitors of cytokines (for example IL-12/IL-23, IL-22, IL-36, and IL-6 inhibitors), anti-adhesion and migration strategies (for example, β7 integrin, sphingosine 1-phosphate receptors, and stem cells), as well as microbial-based therapeutics to decolonize the bed buds (for example, fecal microbiota transplantation and bacterial inhibitors) are currently being evaluated in different phases of controlled clinical trials. This review aims to offer a comprehensive overview of available treatment options and emerging therapeutic approaches for IBD patients. Furthermore, predictive biomarkers for monitoring the therapeutic response to different IBD therapies are also discussed.

Early atherosclerosis and acute vascular events in ulcerative colitis patients-a case series

Introduction: In inflammatory bowel disease uncontrolled inflammation may play a role in the early progression of systemic atheromatosis with increased cardiovascular risk. Endothelial dysfunction is mediated by pro-inflammatory cytokines but also by an increased level of CRP which is involved in the expression of adhesion molecules and atheroma plaque rupture. Tailored treatment with better control of the ulcerative colitis and endoscopic healing might result in decrease risk of atherothrombotic events. Aim: We decided to use a well-established method (vascular Doppler ultrasound with media-intimate index measurement) to detect an increased incidence of endothelial lesions as predictors of early atheromatosis in patients with ulcerative colitis treated with biological or conventional therapy. Material and methods: We prospectively analyzed 25 patients with RCUH with a mean age of 40 years, 16 with biological treatment. The Student t test, the Mann Whitney U test and the ANOVA test were used to compare continuous variables. Results: A discriminant analysis was performed with the presence of atheroma plaque as a dependent variable and several predictor variables, such as age, triglycerides, cholesterol of patients with ulcerative colitis. Univariate ANOVA analyzes revealed that the presence or absence of atheroma plaque differs in the variables predicting the age, INR and ecoIMT of patients with ulcerative colitis (in the age of patients (F = 8.511, degrees of freedom = 11, p = 0.014) Patients ‚INR (F = 50,437, degrees of freedom = 11, p = 0.001) and Patients’ ecoIMT (F = 7,398, degrees of freedom = 11, p = 0.020) In another analysis of discriminatory function s -introduced the predictor variables specific to measuring the evolution of ulcerative colitis, respectively Mayo and Mayo E (age (F = 0.8511, degrees of freedom = 11, p = 0.014), INR (F = 50.437, degrees of freedom = 11, p = 0.001), ecoIMT (F = 7.398, df = 11, p = 0.020) and Mayo (F = 14.885, degrees of freedom = 11, p = 0.003). Conclusions: Age, endoscopic activity, and INR were correlated with predictive ultrasound changes for atheromatosis. Strengths are the prospective nature of the study and weaknesses are the limited number of patients and the fact that most patients were in remission and treated with biologicals, which could create bias in the sense of reducing the atherosclerotic risk directly correlated with active inflammation.

A Serum Biomarker Panel Can Accurately Identify Mucosal Ulcers in Patients With Crohn's Disease.

The Endoscopic Healing Index (EHI) is a serum biomarker panel that can predict endoscopic inflammation in Crohn's disease (CD). Paired serum samples with endoscopies from adult patients participating in a prospective biobank (June 2014 to December 2018) were analyzed post hoc. Diagnostic performance for EHI was assessed against the individual parameters of the Simple Endoscopic Score for CD using previously identified cutoffs. Confounders for EHI performance were identified using logistic regression. A total of 205 CD patients were included (50% male, median age 37 years). An EHI of 20 points was sensitive for ruling out any ulcers (85%; 95% confidence interval [CI], 77%-91%) and large (5-20 mm) or very large (>20 mm) ulcers (93%; 95% CI, 84%-97%). An EHI of 50 points was specific for ruling in any ulcers (86%; 95% CI, 76%-92%) and large or very large ulcers (87%; 95% CI, 79%-92%). After accounting for total extent of inflamed mucosa, strictures, and disease location, each 20-point increase in EHI was associated with a 1.7-fold increased probability for the presence of large or very large ulcers (adjusted odds ratio, 1.7; 95% CI, 1.1-2.6). The EHI was independently associated with ulcer size and accurately identified large or very large ulcers. A cutoff of 50 points can reliably rule in mucosal ulcers and allow for treatment adjustment. A cutoff of 20 points can reliably rule out mucosal ulcers and signal completion of treatment adjustment algorithms.

Biocompatible, adhesive and stable GelMAc/PVAMA/MPDA@Cur hydrogels regulate immune response to improve endoscopic submucosal dissection-induced gastric ulcer healing in vivo

Biocompatible, adhesive and stable GelMAc/PVAMA/MPDA@Cur hydrogels regulate immune response to improve endoscopic submucosal dissection-induced gastric ulcer healing in vivo

Endoscopic mucosal healing and histologic remission in ulcerative colitis: a systematic literature review of clinical, economic and quality-of-life outcomes

Objective This systematic literature review (SLR) assessed the effects of endoscopic mucosal healing and histologic remission on clinical, quality-of-life (QoL), and economic outcomes in adults with ulcerative colitis (UC) in the real-world setting. Methods Literature searches of Embase and MEDLINE (6 July 2020) and conference proceedings (2017–2020) were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Eligible studies included adults with UC with documented endoscopic mucosal healing or histologic remission. Clinical, QoL, and economic outcomes were extracted and narratively synthesized. Results Of 1603 studies screened, 25 met eligibility criteria and collectively included 2813 patients (mean age: 34–60 years). The most commonly reported indices were Mayo endoscopic score (MES) for endoscopic mucosal healing (n = 22, 88%) and Geboes score (n = 5, 20%) for histologic outcomes. The most frequently reported clinical outcome was relapse-free survival (n = 15, 60%). Less commonly reported outcomes were avoidance of colectomy (n = 5, 20%), hospitalization (n = 4, 16%), clinical remission (n = 4, 16%), and steroid-free clinical remission (n = 3, 12%). Most studies reported relapse-free survival rates up to 50% over 6 to 48 months of follow-up in endoscopic mucosal healing cohorts. Studies reporting results by MES demonstrated higher relapse-free survival rates among patients with MES 0 than with MES 1 (32%–100% vs 26%–86%, respectively). Similarly, patients with histologic remission had better relapse-free survival rates over 12 to 24 months of follow-up compared with those without histologic remission (72%–91% vs 40%–63%, respectively). Rates of clinical remission, steroid-free remission, hospitalization, and colectomy avoidance were also better among patients with endoscopic mucosal healing and histologic remission. Two studies examining QoL reported endoscopic mucosal healing was associated with improved QoL. No study reported economic outcomes. Conclusions This SLR demonstrated consistent evidence of improved clinical outcomes among UC patients with endoscopic mucosal healing and histologic remission.

A Computational Platform Integrating a Mechanistic Model of Crohn's Disease for Predicting Temporal Progression of Mucosal Damage and Healing.

IntroductionPhysicians are often required to make treatment decisions for patients with Crohn’s disease on the basis of limited objective information about the state of the patient’s gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn’s disease with a responder classifier to predict temporal changes in mucosal health.MethodsA hybrid mechanistic–statistical platform was developed to predict biomarker and tissue health time courses in patients with Crohn’s disease. Eligible patients from the VERSIFY study (n = 69) were classified into archetypical response cohorts using a decision tree based on early treatment data and baseline characteristics. A virtual patient matching algorithm assigned a digital twin to each patient from their corresponding response cohort. The digital twin was used to forecast response to treatment using the mechanistic model.ResultsThe responder classifier predicted endoscopic remission and mucosal healing for treatment with vedolizumab over 26 weeks, with overall sensitivities of 80% and 75% and overall specificities of 69% and 70%, respectively. Predictions for changes in tissue damage over time in the validation set (n = 31), a measure of the overall performance of the platform, were considered good (at least 70% of data points matched), fair (at least 50%), and poor (less than 50%) for 71%, 23%, and 6% of patients, respectively.ConclusionHybrid computational tools including mechanistic components represent a promising form of decision support that can predict outcomes and patient progress in Crohn’s disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02144-y.

Association of golimumab trough concentrations during maintenance with clinical, biological, endoscopic and histologic remission in patients with ulcerative colitis.

Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. Fifty-two patients were included. Median golimumab trough concentrations (μg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p=0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 μg/g) (2.21 vs. 1.47, p=0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p=0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p=0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p=0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p=0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] μg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.

Therapeutic drug monitoring in inflammatory bowel disease treatments.

Recently, biological drugs have played a leading role in the treatment of inflammatory bowel disease, and therapeutic drug monitoring (TDM) may be useful in maximizing their effectiveness. TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate. We believe that concentration thresholds should be individualized based on patients’ disease severity, extent and phenotype, and therapeutic purposes should also be considered, with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission. Proactive and reactive TDM can help optimize treatment, especially in patients receiving anti-tumour necrosis factor, and guide dose adjustment or drug conversion with lower cost. TDM is a promising approach to achieve precision medicine and targeted medicine in the future.

Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease.

We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after 1 year of therapy in moderate-severe Crohn's disease (CD). This was a pooled analysis of patient-level data from 299 patients with CD from 4 clinical trials. Proportions of patients treated with each biologic were compared for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). Multivariate logistic regression was used to model the relationship between biologics and 1-year outcomes and adjusted for disease duration, concomitant corticosteroid use, and prior antitumor necrosis factor failure. Compared with vedolizumab (4/56 [7.1%]), adalimumab (17/61 [27.9%], adjusted odds ratio [OR]: 5.79, 95% confidence interval [CI]: 1.77-18.95, P = 0.004) and infliximab (39/141 [27.7%], aOR: 4.59, 95% CI: 1.48-14.22, P = 0.008) had superior rates of 1-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naive patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for 1-year ileal EH. However, for large (>0.5 cm) ileal ulcers, infliximab (20/49 [40.8%]) had superior rates of no ileal ulcers compared with vedolizumab (2/23 [8.7%], aOR: 5.39, 95% CI: 1.03-28.05, P = 0.045). No other differences were observed. For colonic disease, compared with ustekinumab (9/31 [29.0%]), adalimumab (30/48 [62.5%], aOR: 3.97, 95% CI: 1.45-10.90, P = 0.007) had superior rates of 1-year EH in the colon, with similar trends observed for infliximab (55/105 [52.4%], aOR: 2.08, 95% CI: 0.82-5.27, P = 0.121). No other differences were observed. In this post hoc analysis, TNF-α antagonists were overall superior to vedolizumab and ustekinumab for achieving 1-year EH in moderate-severe CD patients.