Guillain-Barré Syndrome in a Patient Receiving Anti-Tumor Necrosis Factor for Crohn Disease: Coincidence or Consequence?

BACKGROUND Antibodies against tumor necrosis factor alpha (anti-TNF-alpha) are currently widely used in the treatment of inflammatory bowel diseases (IBD), despite a number of reported adverse effects. Diverse neurologic syndromes, including the Guillain-Barre syndrome (GBS), an immune-mediated disease characterized by evolving ascending limb weakness, sensory loss, and areflexia, have been described in association with anti-TNF-alpha therapy. CASE REPORT A 45-year-old White woman was in follow-up with fistulizing ileocolonic Crohn disease using combination therapy (infliximab plus azathioprine) as CD maintenance therapy. After 3 years of this immunosuppressive therapy, she presented with symmetrical and ascending paresis in the lower limbs, and later in the upper limbs, in addition to reduced reflexes in the knees, 1 day after an infliximab infusion. The patient was hospitalized and treatment for CD was suspended. Neurophysiology studies demonstrated a pattern compatible with acute inflammatory demyelinating polyradiculopathy, with predominantly motor involvement, consistent with Guillain-Barre syndrome (GBS). Clinical, laboratory, and imaging exams were unremarkable. She was treated with intravenous immunoglobulins, with a progressive and complete resolution of neurological symptoms. After 1-year follow-up, she presented with active Crohn disease, and we opted for treating her with vedolizumab, with which she achieved clinical and endoscopic remission. CONCLUSIONS Patients receiving biological therapy with anti-TNF-alpha agents should be monitored for central or peripheral neurological signs and symptoms. The development of GBS can be secondary to anti-TNF-alpha treatment. The positive temporal relationship with TNF-alpha therapy and onset of neurological symptoms reinforces this possibility.

Associations between prior healthcare use, time to diagnosis, and clinical outcomes in inflammatory bowel disease: a nationally representative population-based cohort study.

BACKGROUND: Timely diagnosis and treatment of inflammatory bowel disease (IBD) may improve clinical outcomes. OBJECTIVE: Examine associations between time to diagnosis, patterns of prior healthcare use, and clinical outcomes in IBD. DESIGN: Using the Clinical Practice Research Datalink we identified incident cases of Crohn's disease (CD) and ulcerative colitis (UC), diagnosed between January 2003 and May 2016, with a first primary care gastrointestinal consultation during the 3-year period prior to IBD diagnosis. We used multivariable Cox regression to examine the association of primary care consultation frequency (n=1, 2, >2), annual consultation intensity, hospitalisations for gastrointestinal symptoms, and time to diagnosis with a range of key clinical outcomes following diagnosis. RESULTS: We identified 2645 incident IBD cases (CD: 782; UC: 1863). For CD, >2 consultations were associated with intestinal surgery (adjusted HR (aHR)=2.22, 95% CI 1.45 to 3.39) and subsequent CD-related hospitalisation (aHR=1.80, 95% CI 1.29 to 2.50). For UC, >2 consultations were associated with corticosteroid dependency (aHR=1.76, 95% CI 1.28 to 2.41), immunomodulator use (aHR=1.68, 95% CI 1.24 to 2.26), UC-related hospitalisation (aHR=1.43, 95% CI 1.05 to 1.95) and colectomy (aHR=2.01, 95% CI 1.22 to 3.27). For CD, hospitalisation prior to diagnosis was associated with CD-related hospitalisation (aHR=1.30, 95% CI 1.01 to 1.68) and intestinal surgery (aHR=1.71, 95% CI 1.13 to 2.58); for UC, it was associated with immunomodulator use (aHR=1.42, 95% CI 1.11 to 1.81), UC-related hospitalisation (aHR=1.36, 95% CI 1.06 to 1.95) and colectomy (aHR=1.54, 95% CI 1.01 to 2.34). For CD, consultation intensity in the year before diagnosis was associated with CD-related hospitalisation (aHR=1.19, 95% CI 1.12 to 1.28) and intestinal surgery (aHR=1.13, 95% CI 1.03 to 1.23); for UC, it was associated with corticosteroid use (aHR=1.08, 95% CI 1.04 to 1.13), corticosteroid dependency (aHR=1.05, 95% CI 1.00 to 1.11), and UC-related hospitalisation (aHR=1.12, 95% CI 1.03 to 1.21). For CD, time to diagnosis was associated with risk of CD-related hospitalisation (aHR=1.03, 95% CI 1.01 to 1.68); for UC, it was associated with reduced risk of UC-related hospitalisation (aHR=0.83, 95% CI 0.70 to 0.98) and colectomy (aHR=0.59, 95% CI 0.43 to 0.80). CONCLUSION: Electronic records contain valuable information about patterns of healthcare use that can be used to expedite timely diagnosis and identify aggressive forms of IBD.

Forecasted infliximab concentrations during induction predict time to remission and sustained disease control of inflammatory bowel disease.

BACKGROUND: Infliximab (IFX) exposure is established as a predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease (IBD), and expert consensus is to achieve adequate exposure during induction to achieve and sustain remission. METHODS: We retrospectively evaluated the performance of a Bayesian PK tool in IBD patients starting IFX. Trough IFX serum levels collected immediately before the third (at week 6) and fourth (at week 14) infusions were evaluated from 307 IBD patients (median age=17 years, 50 % females, 83 % with Crohn's disease). Forecasted IFX concentration at the fourth infusion were estimated using serum IFX, antibodies to IFX, albumin and weight determined immediately before the third infusion using population PK calculator with Bayesian prior. The outcome variable was a clinical & biochemical remission status achieved (CRP levels below 3 mg/L in presence of clinical remission). Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression. RESULTS: IFX concentration above 15 µg/mL immediately before the third infusion associated with shorter time to clinical & biochemical remission than concentration below 15 µg/mL without reaching significance (163±14 days vs 200±16 days, respectively; p=0.052). However, using PK parameters at the third infusion, forecasted IFX concentrations above 10 µg/mL immediately before the fourth infusion were significantly associated with a higher rate (HR=1.6 95 %CI: 1.1 to 2.1 p<0.01) and shorter time to remission (148±18 days vs 200±13 days p<0.01). In the presence of IFX concentration above 15 µg/mL at the third infusion, there was a significant 2.5-fold higher likelihood of sustained clinical & biochemical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p<0.01). Forecasted IFX level above 10 µg/mL at fourth infusion associated with significantly 3.9-fold higher likelihood of clinical & biochemical remission as compared to forecasted IFX concentrations below 10 µg/mL (p<0.01). CONCLUSIONS: These data further support that optimized IFX concentrations during induction are associated with enhanced disease control in IBD.

Exploring inflammatory bowel disease therapy targets through druggability genes: a Mendelian randomization study.

Background: Inflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR. Methods: Two-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn's disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability. Result: With our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk. Conclusion: In a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.

Fistulising skin metastases in Crohn's disease: a case report and review of the literature.

BACKGROUND: Metastatic Crohn's disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF). CASE PRESENTATION: We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn's disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient. For our study more than 1600 publications were screened for cases of metastatic Crohn's disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review. CONCLUSION: The successful ustekinumab treatment of a patient with metastatic Crohn's disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases.

Safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of olamkicept: Results from randomized, placebo-controlled, first-in-human phase I trials.

Olamkicept selectively inhibits the cytokine interleukin-6 (IL-6) trans-signaling pathway without blocking the classic pathway and is a promising immunoregulatory therapy for inflammatory bowel disease (IBD). These first-in-human, randomized, placebo-controlled, single- (SAD) and multiple-ascending dose (MAD) trials evaluated olamkicept safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics. Doses tested in the SAD trial included seven single intravenous doses (0.75, 7.5, 75, 150, 300, 600, and 750 mg) and one subcutaneous (SC) dose (60 mg) given to healthy subjects (N = 64), and three intravenous doses (75 mg, 300 mg, and 750 mg) given to patients with Crohn's disease (CD; N = 24). Doses tested in the MAD trial included multiple intravenous doses (75, 300, and 600 mg once weekly for 4 weeks) given to healthy subjects (N = 24). No severe or serious treatment-emergent adverse events (TEAEs) were recorded. The most common TEAEs were headache, nasopharyngitis, and myalgia in the SAD trial, and diarrhea, headache, and cough in the MAD trial. Infusion-related reactions occurred in one and two subjects in the SAD and MAD trial, respectively, leading to treatment discontinuation in the MAD trial. Olamkicept showed dose-independent pharmacokinetics after single and multiple administrations, and there was no major difference in systemic exposure between healthy subjects and patients with CD. Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription-3) was achieved in blood around or above olamkicept serum concentrations of 1-5 µg/mL. Overall, these results suggest that olamkicept is safe and well-tolerated in healthy subjects and patients with CD after single intravenous/SC and multiple intravenous administrations.

[Treatment of multiple sclerosis]. / Behandelmogelijkheden bij multiple sclerose.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, caused by an autoimmune reaction. Treatment options have largely increased over the years. In this article, we present two clinical cases. Patient A has a classic relapsing remitting course of multiple sclerosis with satisfactory effect on second line therapy. Patient B had a stable disease course until a new relapse occurred after the initiation of TNF-alpha blocking therapy because of Crohn's disease. The co-occurrence of multiple auto-immune diseases creates challenges, but also opportunities in choosing the right treatment strategy.

Management of anal fistulas in Crohn's disease after failure of Infliximab.

INTRODUCTION: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. AIM: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. METHODS: A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. CONCLUSION: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.

[A case of hematogenous disseminated tuberculosis in a patient with contradictory reactions treated with thalidomide].

Here we reported a case of a 52-year-old male with a 13-year history of Crohn's disease who developed disseminated tuberculosis after 2 injections of infliximab. The patient was admitted with a chief complaint of fever with headache of 1 month's duration. Mycobacterium tuberculosis DNA was found positive in cerebrospinal fluid and lavage fluid by lumbar puncture and bronchoscopy. He was diagnosed with tuberculous meningitis, pulmonary tuberculosis, tracheobronchial tuberculosis and lymph node tuberculosis. After treatment with anti-tuberculosis and glucocorticoids, the symptoms did not improve, the lesions progressed, and granulomas were formed in the tracheobronchial lumen. These were considered to be contradictory reactions and thalidomide was given together with glucocorticoids. The patient's clinical condition has improved significantly. Treatment was successfully completed after 18 months with 1 HREZLfxLzd/8 HEZCsLzd/1 HEZCs/8 HZCs.

Biologics and targeted synthetic medicines for ulcerative colitis and Crohn's disease.

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases. Recent pivotal phase 3 trials involving treatments like interleukin-23-, sphingosin-1-phosphate- and Janus kinase inhibitors have demonstrated notable effectiveness. However, they have also unveiled significant side effects such as herpes zoster, lymphopenia and bradycardia. The introduction of novel treatments raises valid concerns necessitating increased collaboration with diverse medical specialities to address potentially severe side effects, and this is vital for enhancing the future care of individuals with inflammatory bowel diseases, as argued in this review.

Intraintestinal Heterogeneity of Drug Target Expression in Inflammatory Bowel Disease.

OBJECTIVE: There has been no significant improvement in remission rate in inflammatory bowel disease (IBD) despite several new drugs being introduced in the past two decades. Post-treatment biopsies sometimes show histologic healing in some areas of the intestine while other areas within the same intestine continue to show active inflammation. The aim of this short descriptive study was to determine whether heterogeneous treatment response in IBD may be caused by heterogeneous expression of treatment targets within the same intestine. METHODS: Six cases of Crohn's disease and five cases of ulcerative colitis in which moderate to severe active inflammation was present in at least two biopsies from the same intestine obtained during the same endoscopy procedure were entered in the study. Sections were stained for TNFα and phospho-JAK1 (p-JAK1) using immunohistochemistry. Expression of TNFα and p-JAK1 was recorded as high when the staining intensity was moderate or high, or low when there was no or week staining. The number of eosinophils per high power field was counted in the area of peak density. RESULTS: Different sites within the same intestine from IBD patients with moderate to severe active inflammation may express different levels of TNFα and p-JAK1. For example, in one patient with Crohn's disease with histologically moderate to severe activity in biopsies from the ileum (site 1) and cecum (site 2), there was high expression of p-JAK1 and low TNFα in the ileum biopsy with the exact opposite in the cecum biopsy (low p-JAK1 and high TNFα expression). In this example neither small molecule drug targeting JAK1 nor anti-TNFα biologic given as single agent therapy would be expected to induce histologic remission in both actively inflamed sites in this patient. CONCLUSIONS: The heterogeneous expression of treatment targets within the same intestine may explain why some patients with IBD may not have complete remission on single drug. Studies are needed to determine whether assay for target expression in mucosal biopsies from IBD patients can help to optimize treatment selection.

Prevalence, incidence, and treatment patterns of fistulizing Crohn disease: A US population-based cohort study.

BACKGROUND: Population-based studies for patients with fistulizing Crohn disease (CD), a severe complication of CD, are limited. OBJECTIVE: To report estimates of the prevalence and incidence rates of fistulizing CD in the United States and examine associated treatment patterns among incident cases. METHODS: This retrospective, observational cohort study used a US administrative claims database from January 1, 2016, to December 31, 2019, with at least 365 days' continuous insurance enrollment. The prevalent patient population comprised patients with incident or existing cases of fistulizing CD. Crude, age, and sex-adjusted prevalence and incidence rates of fistulizing CD were estimated. Baseline characteristics, comorbidities, and CD-related medications and medical procedures were examined for patients with fistulizing CD. RESULTS: The overall crude prevalence (prevalent cases: n = 5,082) and incidence rates (incident cases: n = 2,399) between 2017 and 2019 were 25.2 (95% CI = 24.5-25.9) per 100,000 persons and 6.9 (95% CI = 6.6-7.1) per 100,000 person-years, respectively. Age- and sex-adjusted prevalence and incidence rates were 24.9 (95% CI = 24.2-25.6) per 100,000 persons and 7.0 (95% CI = 6.7-7.3) per 100,000 person-years, respectively. Approximately half of all patients with incident fistulizing CD were prescribed biologic therapies within 1 year of an incident fistula diagnosis, with anti-tumor necrosis factor therapies the most widely prescribed biologic class; antibiotic and corticosteroid use was also common. Among the incident cases, approximately one-third of patients required surgery during the follow-up period, most of which occurred within 3 months of the index date. CONCLUSIONS: This study reports age- and sex-adjusted prevalence and incidence rates for fistulizing CD of 24.9 per 100,000 persons and 7.0 per 100,000 person-years, respectively. As a concerning complication of CD, first-year treatment of fistulas in the United States commonly includes anti-tumor necrosis factor therapy, and there is a considerable surgical burden.

Magnolin inhibits intestinal epithelial cell apoptosis alleviating Crohn's disease-like colitis by suppressing the PI3K/AKT signalling pathway.

BACKGROUND AND AIMS: Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved. METHODS: Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis. RESULTS: The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro. CONCLUSIONS: MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD.

Evaluating the pharmacokinetics of upadacitinib for the treatment of moderate-to-severe Crohn's disease.

INTRODUCTION: Janus kinases (JAK) are enzymes involved in signaling pathways that activate the immune system. Upadacitinib, an oral small molecule, is the first JAK inhibitor approved by FDA and EMA for the treatment of moderately to severely active Crohn's disease (CD), following successful phase II and III trials. Compared to other JAK inhibitors, upadacitinib has a high selectivity toward JAK1. This characteristic could improve its efficacy and safety. AREAS COVERED: This review provides an overview of the available knowledge on the pharmacokinetics of upadacitinib as induction and maintenance therapy for CD. EXPERT OPINION: The approval of newer targeted small molecules drug, including JAK inhibitors, marked a significant advancement in terms of effectiveness. In fact, the oral administration, the rapid absorption, the excellent bioavailability and the short serum time of maximum concentration are some of the advantages compared to biologics. The selective inhibition of JAK1 by upadacitinib allows for high efficacy while maintaining a reliable safety profile.

Overview to Challenges in IBD 2024-2029.

The mission of the Crohn's & Colitis Foundation is to cure Crohn's disease and ulcerative colitis and to improve the quality of lives of patients living with these diseases-in other words, to care and cure. To achieve these missions, there is a need to identify and prioritize research gaps and approaches to address these gaps, which is the aim of Challenges in IBD 2024. The Foundation convened close to 80 experts in inflammatory bowel disease (IBD), including researchers, clinicians, patients and caregivers, funders, industry representatives, and Foundation scientific staff and organized them into 5 workgroups, one for each of the 5 Challenges topics: Preclinical Human IBD Mechanisms, Environmental Triggers, Precision Medicine, Novel Technologies, and Pragmatic Clinical Research. The findings of these groups outline a research agenda that intends to change the research paradigm in IBD by introducing 2 concepts in the course of IBD that warrant specific focus: interception (during the preclinical phase) and restoration of normal physiology after remission is achieved. We hope these reviews will stimulate innovations in our understanding and management of IBD.

Metronidazole-Induced Encephalopathy With Probable Crohn Encephalitis: A Case Report.

OBJECTIVES: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy. METHODS: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement. RESULTS: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired. CONCLUSIONS: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology.

Infliximab-induced amicrobial pustulosis of the folds in a patient with Crohn disease.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study.

OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.

[Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease].

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.