Infliximab In Crohn Research Articles

Tracing the historical foundations of infliximab in Crohn’s disease treatment: a cited reference analysis

IntroductionThe use of infliximab to treat Crohn’s disease patients has been evaluated for decades. The current work aimed to identify the historical roots of this research topic.MethodsThe literature database Web of Science Core Collection was searched to identify relevant papers. Cited reference analysis on the identified literature set was performed using CRExplorer, a dedicated bibliometric software. The disruption index was computed with an automated routine described by Leydesdorff and Bornmann, which is freely available online. Based on data from citation count and reference list, the disruption index can range from −1 to +1, with −1 meaning a continuity from existing research and +1 meaning a disruption.ResultsThis analysis successfully identified key references dealing with infliximab use on Crohn’s disease patients, such as the original report that introduced the Crohn’s Disease Activity Index (CDAI) in 1976, the first case series reporting a favourable outcome of infliximab infusion on 10 patients published in 1995, the first randomized controlled trial published in 1997, the ACCENT I and ACCENT II trials published in 1999 and 2002, and a couple of European consensus guidelines on the diagnosis and management of Crohn’s disease.ConclusionCited reference analysis could reveal the historical origins of the use of infliximab in treating Crohn’s disease. Highly cited references included CDAI, important early clinical studies, and European consensus guidelines. The important cited references identified by the analysis provided solid foundation to support subsequent research.

Subcutaneous infliximab in Crohn’s disease patients with previous immunogenic failure of intravenous infliximab

PurposeImmunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective.MethodsIn a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn’s disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12.ResultsTwenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%).ConclusionSubcutaneous infliximab treatment of Crohn’s disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.

Prediction of early remission after infliximab in Crohn’s disease using baseline microbiome and metabolomics

To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC–MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.

Clinical and Biological Lupus Induced by Infliximab in Crohn's Disease

The use of anti-TNFs in Crohn's disease (CD) is often associated with the appearance of antinuclear antibodies, and more rarely with anti-native DNA antibodies. Anti-TNF-induced lupus remains exceptional. We report the case of a 52-year-old woman, followed for colonic Crohn's disease, treated with Infliximab. After 12 months of treatment with anti-TNF alpha (Infliximab), the patient developed clinical and biological lupus with positive antinuclear antibodies (ANA) and anti-native DNA antibodies (IgG). Infliximab treatment was discontinued. Six months after stopping the treatment, the patient had no recurrence of clinical signs, and immunological examinations showed a marked decrease in total ANA and anti-native DNA antibodies (IgG).

CT-based pancreatic radiomics predicts secondary loss of response to infliximab in biologically naïve patients with Crohn’s disease

ObjectivesPredicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn’s disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD.MethodsThree models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation.ResultsIn total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872.ConclusionsThe first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients.Critical relevance statementThis study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD.Key points• The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn’s disease.• The model achieved satisfactory predictive accuracy, calibration ability, and clinical value.• The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens.Graphical

P1049 Effectiveness and safety of subcutaneous infliximab in Crohn’s disease patients with immunogenic failure of intravenous infliximab

Abstract Background Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous compared to intravenous infliximab. However, it is unknown whether re-exposure of patients with immunogenic failure of IFX to its subcutaneous formulation is safe and effective. Here, we analysed the safety and effectiveness of subcutaneous IFX (CT-P13) in patients with Crohn’s disease (CD) and history of secondary loss of response of intravenous IFX due to anti-drug antibodies (ADA). Methods In a retrospective analysis conducted at medical centers in Germany (Dresden) and the Czech Republic (Prague), patients with clinical (Harvey-Bradshaw Index ≥ 5) and/or biochemical (faecal calprotectin &amp;gt;250 µg/g) active CD and previous treatment failure in the context of IFX immunogenicity underwent re-exposure to subcutaneous IFX. Treatment was initiated with either 4 subcutaneous injections 120 mg CT-P13 weekly followed by biweekly injections, or directly with 120 mg CT-P13 subcutaneous biweekly. Harvey-Bradshaw Index, faecal calprotectin, IFX serum concentration and ADA were assessed until month 12. Results Twenty CD patients were included (table 1). The majority of patients (90 %) had previous treatment with ≥ 3 biologics. 75% and 50 % of patients continued IFX treatment until month 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients (10%) discontinued IFX due to delayed hypersensitivity. Lack of treatment effectiveness led to infliximab withdrawal in 7 cases (35%) and one patient (5%) was lost to follow up after month 6. IFX serum concentrations increased from baseline (median 0 µl/ml ± 0 interquartile range/IQR) until month 12 (median 22.8 µl/ml, 10.0 IQR), while ADA levels decreased (50.6 AU/ml, 48.3 IQR and 0.0 AU/ml, 0 IQR at baseline and month 12, respectively). Clinical remission at month 12 was observed in 27% and biochemical remission in 38% of patients with active Crohn's disease at baseline. 67 % of patients with clinical inactive Crohn's disease at baseline remained in clinical remission until month 12. Conclusion Subcutaneous infliximab after previous failure and immunogenicity of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn’s disease.

P995 Development and validation of a deep learning model based on histological characteristics to predict primary non-response of infliximab in Crohn's disease

Abstract Background Predicting primary non-response to infliximab (IFX) is important to select the optimal therapy and utilize personalized management in patients of Crohn’s disease (CD). This study aimed to develop and validate a deep learning (DL) model based on histological characteristics for predicting primary non-response to IFX in CD. Methods A training cohort and a validation cohort were recruited from the First Affiliated Hospital of Sun Yat-sen University. Clinical features, serological biomarkers, imaging features and histological characteristics of colonoscopy biopsy at baseline of IFX therapy were obtained as candidate predictors. Primary non-response was assessed at week 14. We developed a model using a multi-instance learning framework. This model combines patch-level features from whole slide images (WSI) with multi-modal information, together with pre-treatment image features and clinical features, to predict the response to infliximab (IFX) therapy. Finally, the model was validated for area under the curve (AUC) in a reference validation cohort. Results A total of 131 patients were included in the derivation cohort. The DL model based on pathologic features only had an under-the-curve receiver operating characteristic (AUROC) value of 0.87 in the 10-fold cross-validation cohort. The mean AUROC for the model combining pathologic and radiographic features was 0.88. The DL model achieved the highest AUROC value of 0.91 when combining pathological, radiomics and clinical features (Figure 1). When the pathological film was visualized by attention thermography, it was found that the ulcerated tissue was focused on, especially in areas dominated by neutrophils, lymphocyte aggregation and abnormal crypt structure. Conclusion The study developed several accurate DL models for predicting primary non-response to IFX by WSI. The DL model combining pathological, radiomics and clinical features achieving best performance. This model may help clinicians select appropriate therapeutic strategy and avoid unnecessary exposure to IFX in CD patients.

Deep-Learning, Radiomics and Clinic Based Fusion Models for Predicting Response to Infliximab in Crohn's Disease Patients: A Multicentre, Retrospective Study.

Accurate prediction of treatment response in Crohn's disease (CD) patients undergoing infliximab (IFX) therapy is essential for clinical decision-making. Our goal was to compare the performance of the clinical characteristics, radiomics and deep learning model from computed tomography enterography (CTE) for identifying individuals at high risk of IFX treatment failure. This retrospective study enrolled 263 CD patients from three medical centers between 2017 and 2023 patients received CTE examinations within 1 month before IFX commencement. A training cohort was recruited from center 1 (n=166), while test cohort from centers 2 and 3 (n=97). The deep learning model and radiomics were constructed based on CTE images of lesion. The clinical model was developed using clinical characteristics. Two fusion methods were used to create fusion model: the feature-based early fusion model and the decision-based late fusion model. The performances of the predictive models were evaluated. The early fusion model achieved the highest area under characteristics curve (AUC) (0.85-0.91) among all patient cohorts, significantly outperforming deep learning model (AUC=0.72-0.82, p=0.06-0.03, Delong test) and radiomics model (AUC=0.72-0.78, p=0.06-0.01). Compared to early fusion model, the AUC values for the clinical and late fusion models were 0.71-0.91 (p=0.01-0.41), and 0.81-0.88 (p=0.49-0.37) in the test and training set, respectively. Moreover, the early fusion had the lowest value of Brier's score 0.15-0.12 in all patient set. The early fusion model, which integrates deep learning, radiomics, and clinical data, can be utilized to predict the response to IFX treatment in CD patients and illustrated clinical decision-making utility.

A novel role of prognostic nutritional index in predicting the effectiveness of infliximab in Crohn's disease

Objective To investigate the predictive value of the prognostic nutritional index (PNI) for the effectiveness of infliximab (IFX) in patients with Crohn's disease (CD). Methods All data were retrospectively collected from Xiangya Hospital, Central South University between January 2016 and September 2021. Clinical remission at 52 weeks is the primary endpoint. Results Altogether, 193 CD patients were enrolled. PNI can identify clinical remission (p = 0.004), and the optimal cut-off value of the PNI was 39.2. 92/116 (79.3%) and 44/77 (57.1%) in the high- and low-PNI groups were in clinical remission at week 52 (p = 0.001). Patients with low PNI have poor general health at baseline. The body mass index, hemoglobin, platelet (PLT), serum creatinine, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Crohn's disease activity index (CDAI), and location of disease significantly differed between the two groups (p < 0.05). PNI was negatively correlated with CRP, ESR, PLT and CDAI (p < 0.05). The lower PNI, smoking history, and higher CDAI at baseline were the independent risk factors of disease activity at 52 weeks (p < 0.05). The high-PNI group is less likely to develop poor outcomes (p = 0.033). Conclusion The PNI may serve as a novel and promising biomarker in predicting the effectiveness of IFX and contribute to targeted management in CD.

Retreatment with infliximab in Crohn’s disease: Is there a benefit?

Retreatment with infliximab in Crohn’s disease: Is there a benefit?

Anal Carcinoma in Patients with Crohn's Disease: Three Cases Report and Literature Review

Background: Anal cancer in patients with Crohn's disease (CD) is rare, and the relationship between infliximab and anal cancer is not clear yet. The present study aimed to report three patients with CD complicated with anal cancer who used infliximab with their basic features. Case presentation: Three cases were reported, including two females and one male, aged 29-56 years old. All of them developed perianal lesions during the period of Crohn's disease. All three patients had used infliximab for Crohn's disease before the diagnosis of anal cancer, except one patient who stopped using infliximab three times due to allergy; the other two patients had used infliximab until the diagnosis of anal cancer. Two patients had a good prognosis with early therapeutic intervention. Conclusion: Based on the results, Chinese and Western patients with Crohn's disease who developed anal carcinoma had similar features. Conventional perianal evaluation is important in patients with Crohn's disease. The association between infliximab therapy and anal cancer has not been fully established and needs to be fully evaluated before the use of infliximab in Crohn's disease

S8 How Can We Predict the Development of Antibodies to Infliximab in Crohn’s Disease?

Background: Anti-tumour necrosis factor-α (anti-TNF-α) therapy is an effective treatment for the management of Crohn’s disease (CD). However, treatment failure is common. The aim of this study was to identify predictors of anti-TNF-α therapy failure. Methods: Retrospective single-center study including anti-TNF-α naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), faecal calprotectin, infliximab serum concentrations and the presence of antibodies to infliximab (ATI). Anti-TNF-α therapy failure was defined as the development of ATI at 6 and 12 months, absence of clinical response at 6 months, absence of clinical remission or absence of objective response at 12 months. Clinical response was defined as a reduction in Harvey-Bradshaw index (HBI) of ≥3 points comparing with initial value or HBI <5 points if initial HBI ≥7 points and clinical remission as HBI ≤4 points. Objective response was assessed by endoscopic studies, defined by improvement of mucosal inflammation and absence of deep ulcerations, or imaging, defined as improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement. Results: A total of 53 CD patients were included, 30 were female (56.6%), with a mean age at the beginning of treatment of 39 ± 2 years. Considering the Montreal classification, 31 patients had ileal disease (58.5%), 7 colonic (13.2%) and 15 ileocolonic disease (28.3%); 22 patients had nonstricturing, nonpenetrating disease (41.5%), 22 stricturing (41.5%) and 9 penetrating disease (17.0%). Eleven patients had perianal disease (20.8%). A total of 26 patients (49.1%) were treated with combination of anti-TNF-α and immunomodulatory therapy (thiopurine or methotrexate). Anti-TNF-α therapy failure occurred in 21 patients (39.6%). At 6 months, the development of ATI occurred in 6 patients (11.3%) and absence of clinical response in 9 patients (17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0% of patients. At 6 months, the development of ATI was significantly higher in patients with lower infliximab serum concentrations at week 14 (with antibodies 5.9 ± 3.2 µg/mL vs without 14.3 ± 7.7 µg/mL, P < 0.001). Additionally, the development of ATI was significantly higher in patients with a higher initial value of ESR (with antibodies median 35 vs without median 13, P = 0.045). The infliximab serum concentrations at week 14 (AUC 0.828; P = 0.009; with sensitivity 0.833 and specificity 0.404 for values ≤11.6) and the initial value of ESR (AUC 0.754; P = 0.045; with sensitivity 0.833 and specificity 0.468 for values ≥15) had very good and good discriminative capacity, respectively, in predicting the development of ATI. No statistically significant differences were found in initial values of CRP and faecal calprotectin, between both groups. Moreover, the other definers of anti-TNF-α therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of ESR, CRP and faecal calprotectin. Conclusion(s): Infliximab serum concentration after induction therapy is the most important factor in the development of ATI, influencing treatment response, regardless of the combination of anti-TNF-α therapy with immunomodulatory therapy. A higher initial value of ESR can also predict the development of ATI.

P081 Therapeutic Drug Monitoring of infliximab in Crohn’s Disease: Cut-off points during maintenance therapy

Abstract Background Therapeutic drug monitoring of infliximab in Crohn’s disease is necessary to optimize treatments. However, infliximab serum levels are not well defined. The aim of the study was to find our cut-off of infliximab serum levels in Crohn’s disease patients in remission in clinical practice. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy. Methods Observational, retrospective and single-center study of patients diagnosed with Crohn’s disease on maintenance therapy with infliximab from January 2019 to July 2020. Infliximab trough levels and antibodies to infliximab were measured at least three times, after 6 months of treatment. The tests were performed using enzyme linked immunosorbent assay. Clinical remission was defined using the Harvey Bradshaw index ≤4. The interpretation of data was by ROC analysis. Results 105 Crohn’s disease patients were included in the study, 57.1% men, with a median age at diagnosis of 26 years. The rest of the characteristics are in table 1. The best infliximab level cut-off point classifying patients in clinical remission was 4 μg/ml with an area under the curve of 0.801 (figure 1 and 2). Median infliximab trough levels were significantly higher when patients achieved clinical remission [4.8 (3–8) μg/ml] versus [0.59 (0.1–2.4) μg/ml]. In the multivariate analysis we observed that the variables age, time on infliximab treatment and time of disease evolution were associated with non-remission (table 2). Conclusion Infliximab levels are an objective parameter related to clinical remission in maintenance therapy in patients with Crohn’s disease. Our cut-off point associated with clinical remission was 4 μg/ml.

MRI-Based Radiomic Signature Identifying Secondary Loss of Response to Infliximab in Crohn's Disease.

Up to 50% of patients with Crohn's disease (CD) experience secondary loss of response (SLR) to infliximab. Patients with SLR may show clinical signs of iron deficiency as a result of inflammation despite being iron-replete. The magnetic resonance imaging (MRI)-based radiomic index, R2*, can detect changes in iron metabolism. Therefore, the R2* parameter has considerable potential for detection of SLR to infliximab. The aims of this study were to explore the correlation between R2* and inflammation and to develop a non-invasive nomogram based on R2* to identify SLR to infliximab in patients with CD. Three hundred and twenty-two infliximab-treated patients with CD who underwent magnetic resonance enterography within 2 weeks before or after 54 weeks of infliximab therapy were divided into training and validation datasets at a ratio of 8:2. Point-biserial analysis was conducted to confirm the relationship between R2* and inflammation. A multivariate logistic regression model was created using R2*, CRP and hemoglobin (OR, 1.10, 1.04 and 0.98; P < 0.05). Receiver-operating characteristic curves and the Hosmer-Lemeshow test were used to assess the performance of the model. A correlation between R2* and inflammation was identified. Different trends in R2* and iron status indices were observed between patients with responsive and non-responsive CD, which is worthy of further study. The model was converted to a visualized nomogram that had a good ability to discriminate the outcomes of infliximab therapy with an area under the curve of 0.723 (95% CI, 0.661–0.785) in the training dataset and 0.715 (95% CI, 0.587–0.843) in the validation dataset. We confirmed a correlation between R2* and inflammation in patients with CD. Based on the MRI-based radiomic signature, a novel nomogram was established and validated to facilitate individualized identification of SLR to infliximab in patients with CD.

A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn's Disease.

BackgroundInfliximab is effective in inducing and maintaining remission in patients with Crohn’s disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.MethodsFrom January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms.ResultsAmong the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab.ConclusionsMMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.

Early Start of Infliximab in Crohn's Disease Increases Rates of Endoscopic Remission and Decreases Stenosis Formation: Experiences From a Single Center Cohort.

Over 10 years ago, the step-up/top-down trial demonstrated favorable outcomes of Crohn's disease (CD) after early initiation of infliximab (IFX) in patients with CD. However, data on long-term effects of this treatment strategy in daily clinical practice are scarce. This retrospective study investigated effects of early (<24 months after diagnosis) versus late intervention (>24 months) of IFX in CD on endoscopic remission (ER) rates, surgery rates, and course of CD, long term. Overall, 242 CD patients (94 early, 148 late intervention) were started on IFX and followed for 24 months. Sixty-one patients with early and 86 with late intervention underwent endoscopy after start of IFX. After IFX induction, 90.3% of patients with early versus 87.8% with late intervention were in clinical remission (P = .676), compared to 89.1% versus 85.8% after 24 months (P = .554). Almost half of patients with early IFX (45.9%, n = 28/61) achieved ER within 24 months compared to only one forth with late IFX intervention (25.6%, n = 22/86, P = .013). In addition, significantly less patients with early IFX intervention (9.8%, n = 6/61) developed intestinal stenosis during 24 months follow-up compared to late IFX start (29.1%, n = 25/86, P = .007). Logistic regression revealed early IFX intervention as only relevant factor achieving ER with an odds ratio of 2.386 (95% confidence interval [1.1180; 4.825], P = .016). Our data on early IFX therapy in CD support early IFX intervention with more patients achieving ER, and less patients developing stricturing disease behavior. Early IFX intervention could therefore change the course of CD.

Clinical Decision Support Tool for Infliximab in Crohn’s Disease

Biologic treatment options for Crohn's disease (CD) are increasing and providers will need enhanced support in integrating these therapies into routine practice. Using phase 3 clinical trial programs in CD, we have previously built and validated clinical decision support tools for achieving clinical remission (CREM) with vedolizumab and ustekinumab in CD.1-4 We now aim to develop a clinical decision support tool for infliximab in CD.

A Novel Radiomics Nomogram for the Prediction of Secondary Loss of Response to Infliximab in Crohn's Disease.

PurposeThe prediction of the loss of response (LOR) to infliximab (IFX) is crucial for optimizing treatment strategies and shifting biologics. However, a secondary LOR is difficult to predict by endoscopy due to the intestinal stricture, perforation, and fistulas. This study aimed to develop and validate a radiomic nomogram for the prediction of secondary LOR to IFX in patients with Crohn’s disease (CD).Patients and MethodsA total of 186 biologic-naive patients diagnosed with CD between September 2016 and June 2019 were enrolled. Secondary LOR was determined during week 54. Computed tomography enterography (CTE) texture analysis (TA) features were extracted from lesions and analyzed using LIFEx software. Feature selection was performed by least absolute shrinkage and selection operator (LASSO) and ten-fold cross validation. A nomogram was constructed using multivariable logistic regression, and the internal validation was approached by ten-fold cross validation.ResultsPredictors contained in the radiomics nomogram included three first-order and five second-order signatures. The prediction model presented significant discrimination (AUC, 0.880; 95% CI, 0.816–0.944) and high calibration (mean absolute error of = 0.028). Decision curve analysis (DCA) indicated that the nomogram provided clinical net benefit. Ten-fold cross validation assessed the stability of the nomogram with an AUC of 0.817 and an accuracy of 0.819.ConclusionThis novel radiomics nomogram provides a predictive tool to assess secondary LOR to IFX in patients with Crohn’s disease. This tool will help physicians decide when to switch therapy.

Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease.

Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn’s disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The “one-hour FMT protocol” was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43–6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001–0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831

Development and Validation of an Interleukin-6 Nomogram to Predict Primary Non-response to Infliximab in Crohn’s Disease Patients

Background: The primary non-response (PNR) rate of infliximab (IFX) varies from 20 to 46% for the treatment of Crohn’s disease (CD). Detected PNR reduces the improper use of specific treatments. To date, there is hardly any knowledge regarding early markers of PNR. The aim of this study was to evaluate the role of Interleukin-6 (IL-6) as an early predictor of PNR of IFX for the treatment of CD. Methods: We enrolled 322 bio-naïve patients diagnosed with CD from January 2016 to May 2020. Primary response was determined at week 14. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. GEO data were analyzed to identify potential mechanisms of IL-6 in IFX therapy for CD. Results: PNR occurred in 31.06% (100 of 322) patients who were assessable at week 14. IL-6 levels significantly decreased after IFX therapy (p < 0.001). The validation model containing IL-6 presented enhanced discrimination with an AUC of 0.908 and high calibration. Decision curve analysis (DCA) indicated that the model added extra predictive value. GEO data confirmed the IL-6 levels were increased in the PNR group and IL-6-related differentially expressed genes (DEGs) were enriched in the inflammatory response. Conclusions: We concluded that IL-6 may be used as a predictive factor to assess the risk of PNR to IFX therapy.