Luminal Disease Research Articles

Factors associated with time to clinical remission in pediatric luminal Crohn's disease: A retrospective cohort study.

Background and AimData on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD.MethodsPatients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients' medical records. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological, and therapeutic factors on time to clinical remission.ResultsA total of 654 patients were included in the study. There was no change in the time to clinical remission over the decade. Female sex in adolescents (adjusted bêta regression coefficient [aβ] = 31.8 days, P = 0.02), upper digestive tract involvement (aβ = 46.4 days, P = 0.04) perianal disease (aβ = 32.2 days, P = 0.04), presence of active inflammation on biopsies at diagnosis (aβ = 46.7 days, P = 0.01) and oral 5‐aminosalicylates (5‐ASA) exposure (aβ = 56.6 days, P = 0.002) were associated with longer time to clinical remission. Antibiotic exposure (aβ = −29.3 days, P = 0.04), increased eosinophils (aβ = −29.6 days, P = 0.008) and combination of exclusive enteral nutrition with tumor‐necrosis‐factor‐alpha (TNF‐alpha) inhibitors as induction therapy (aβ = −36.8 days, P = 0.04) were associated with shorter time to clinical remission.ConclusionIn children with newly diagnosed Crohn's disease, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF‐alpha inhibitors was associated with faster clinical remission.

Perianal disease onset age is associated with distinct disease features and need for intestinal resection in perianal Crohn\u2019s disease: a ten-year hospital-based observational study in China

Background and aimsThe significance of different ages of perianal disease (PD) onset in patients with perianal Crohn’s disease (PCD) remains unknown. We aimed to investigate the impact of paediatric-onset PD (POP) and adult-onset PD (AOP) on the Crohn’s disease (CD) course in a Chinese cohort.MethodsThe medical records of diagnosed PCD patients from 2008 to 2018 were reviewed retrospectively. The cumulative incidence and predictors of intestinal resection were calculated using the Kaplan–Meier and logistic regression analysis.ResultsComplex perianal fistulas (71.7% vs 50.0%, p = 0.011) and infliximab (IFX) treatment (33.3% vs 22.0%, p = 0.044) were more common among the POP patients (age < 18 years old, n = 84). A younger PD onset age (15.1 ± 2.9 vs 30.2 ± 10.5 years, p < 0.001) and shorter PCD diagnostic delay (12 vs 24 months, p = 0.033) was found in the POP cohort. AOP patients (age ≥ 18 years old, n = 209) had a higher rate of current smoking (12.9% vs 4.8%, p = 0.040), stricturing behaviour (42.1% vs 27.4%, p = 0.024) and intestinal resection (21.1% vs 4.8%, p = 0.001). The cumulative probability of intestinal resection in AOP patients was higher than that in POP patients (p = 0.007). In multivariable analysis, AOP (OR: 4.939, 95% CI 1.538–15.855, p = 0.007), stricturing behaviour (OR: 1.810, 95% CI 1.008–3.251, p = 0.047) and rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were predictive factors for CD-related intestinal resection in all PCD patients. AOP patients with complex perianal fistula (OR: 2.257, 95% CI 1.041–4.891, p = 0.039) and POP patients with rectal inflammation (OR: 3.166, 95% CI 1.119–8.959, p = 0.030) were more likely to suffer intestinal resection. The IFX administration significantly decreased the rate of intestinal resection in AOP patients (r = − 0.900, p = 0.037).ConclusionsThe AOP patients have more complicated luminal disease and higher rate of intestinal resection than COP patients. The perianal diseases onset-age can provide clinical treatment guidance for individual management of CD patients.

St Gallen 2019 guidelines understage the axilla in lobular breast cancer: a population-based study.

The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy. Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort. Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001). Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.

IgG4-related disease as a rare cause of gastric outlet obstruction: a case report and literature review

BackgroundIgG4-related disease involvement of the digestive tract is very rare. In few reported cases of isolated gastric/duodenal IgG4-related disease, none of which resulted in luminal obstruction.Case presentationA 59 years old female presented with longstanding gastrointestinal symptoms. CT showed mural thickening of the proximal duodenum. Gastroscopy showed antral ulcer extending into the duodenum with outlet obstruction and biopsy showed acute on chronic duodenitis. Whipple’s procedure was performed and IgG4-related disease was diagnosed on final pathology. Symptoms were revolved on mycophenolate mofetil and prednisone with no recurrence.ConclusionsOur case is the only reported case with gastric outlet obstruction secondary to gastroduodenal IgG4-related disease. The diagnosis should be considered in the differential diagnosis of unexplained duodenal stricture, gastric outlet obstruction or gastrointestinal ulceration. IgG4-related disease usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-related disease remains to be determined.

C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case-Control and Meta-Analysis Study.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

Infliximab Concentrations during Induction Are Predictive for Endoscopic Remission in Pediatric Patients with Inflammatory Bowel Disease under Combination Therapy

To study infliximab (IFX) pharmacokinetics in children with inflammatory bowel disease (IBD) during induction therapy to predict outcome and explore if other covariates influenced outcome. All children with IBD starting IFX therapy (5mg/kg at weeks 0, 2, 6, and 12) for active luminal disease from May 2017 to May 2019 were included and followed prospectively. Patients were sampled at multiple timepoints during induction (trough concentrations and peak concentration at weeks 0, 2, 6, and 12, and intermediate concentration at weeks 1-4). IFX concentrations and cumulative drug exposure were correlated with outcome at 6months. Endoscopic remission was defined as Simple Endoscopic Score for Crohn's Disease of <3 or Mayo endoscopic subscore of 0, and deep remission as endoscopic with clinical remission (Pediatric Ulcerative Colitis Activity Index/Pediatric Crohn's Disease Activity Index of <10). There were 252 serum induction concentrations obtained from 32 patients (81% on concomitant thiopurines). Children in endoscopic remission (all in deep remission) at 6months had significantly higher drug concentrations from week 4 onward. A receiver operating characteristics curve analysis identified IFX trough concentrations at week 12 of ≥5.0μg/mL and area under the curve at weeks 0-12 of ≥4056.0μg∗day/mL as the minimal target to achieve endoscopic remission at 6months (area under the receiver operating characteristics curve, 0.796 [95% CI, 0.62-0.97] and area under the receiver operating characteristics curve, 0.778 [95% CI, 0.61-0.94], respectively). In addition, our findings suggest that proteomic analysis may help to understand IFX response. Higher IFX exposure during induction therapy in pediatric patients with IBD is associated with significantly better endoscopic and deep remission rates at 6months. Drug concentrations differentiate remitters from nonremitters from week 4 after induction onward.

146P Prognostic impact of HER2-low expression according to the oncotype Dx recurrence score in hormone receptor-positive early breast cancer

The prognostic role of human epidermal growth factor receptor 2 (HER2) low expression in estrogen receptor (ER)-positive, HER2-negative breast cancer is not well described. The aim of this study is to compare disease characteristics and outcomes between HER2-low to HER2-0, in early-stage luminal disease.

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer. MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status. Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression. ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.

HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer

Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. In total, 855 HER2-negative patients were identified. The median follow-up was 59months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

The impact of endogenous estrogen exposures on the characteristics and outcomes of estrogen receptor positive, early breast cancer

BackgroundMenstrual and parity history might impact the risk for breast cancer. Data on the impact of these factors on other tumor characteristics are limited.MethodsA single center retrospective cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative, early breast cancer whose tumors were sent to OncotypeDX analysis. The prespecified subgroups were investigated: age of menarche (< 12 vs. ≥ 12 years), number of deliveries (0 vs. ≥ 1 childbirth and ≥ 5 childbirth vs. other), age of first delivery (≥ 30 years vs. younger age) and postmenopausal compared to premenopausal. The impact of age of menopause was also assessed categorically, using early (< 45 years) and late age of menopause (> 55 years). Differences in tumor characteristics were evaluated using T-test or Mann Whitney for continuous variables or Fisher’s exact test for categorical variables. Outcomes were assessed by Kaplan–Meier survival analysis, with the log-rank test.ResultsA total of 620 women were included. After median follow-up of 10.4 years, early menopause was associated with significantly worse disease-free survival (HR = 2.26, p = 0.004) and overall-survival (HR = 2.60, p = 0.004), and multiparity was associated with significant worse disease-free survival (HR = 2.16, p = 0.026). These differences remain significant in multivariate analyses. Post-menopausal women were more likely to have stronger ER intensity (p = 0.002) but progesterone receptor (PR) positivity was less frequent (p = 0.009(. Early age of menarche was associated with PR positivity (p = 0.039). No other associations were found between the evaluated subgroups and tumor characteristics.ConclusionsThe impact of endogenous estrogen exposure had little effect on breast cancer characteristics of early stage, luminal disease. Early menopause and multiparity were associated with worse outcome.

Recognising and Treating Complicated Fissuring Perianal Crohn Disease: A South-East Scotland Cohort Study.

Fissuring perianal Crohn disease (CD) is not recognised as a perianal phenotype in Montreal/Paris inflammatory bowel disease classifications; however, can occasionally present as complicated disease with severe perianal pain driving increasingly intensive medical therapy despite well controlled luminal disease. We identified a regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland over a 19-year period (1999-2018), and conducted a retrospective review of complicated fissuring perianal CD causing severe pain related to anal sphincter complex spasm at defecation. Two hundred forty-seven new cases of paediatric CD were diagnosed with complicated fissuring perianal disease identified in 4 described cases (cumulative incidence 1.6%). These patients with marked fissuring and refractory anal sphincter complex spasm required neurostimulation-guided, 4-quadrant, anal intrasphincteric botulinum toxin (BT). All experienced immediate success, measured by cessation of spasms, with variable ongoing symptom relief after median (range) 3 (2-5) BT injections.

Prognostic value of SUVmax in breast cancer and comparative analyses of molecular subtypes: A systematic review and meta-analysis.

Background:To assess the prognostic capability of the maximum standardized uptake values (SUVmax) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes.Methods:The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUVmax; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUVmax. The pooled HR was estimated using random-effects model according to the results of heterogeneity.Results:Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUVmax in the primary tumor and ALN were 3.01 (95% CI 1.83–4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15–12.01; I2 = 92%; P = .03), respectively. Patients with higher SUVmax demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUVmax in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31–5.37; I2 = 27%; P = .007).Conclusions:SUVmax from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUVmax.

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

The majority of patients with Crohn's disease (CD) will not achieve endoscopic remission on current therapy. Addition of tofacitinib to biologics may improve remission rates. We retrospectively assessed safety and clinical and endoscopic effectiveness of off-label tofacitinib and biologics for CD. We identified 19 patients treated with tofacitinib and a biologic for refractory CD between 2017 and 2019. Tofacitinib was added for luminal disease on colonoscopy (n = 13), luminal disease on capsule (n = 3), and pyoderma gangrenosum (n = 3). The mean age was 41.2 years (28-62), mean disease was duration 16.9 years (6-36), and prior exposure to biologics was a median of 4 (1-6). Mean treatment duration was 9.6 months (SD, 3.3). Adverse events (AEs) were reported in 36.8% of patients, most commonly minor infection or CD flare, and no patients had a serious AE; 80.0% (n = 8) achieved clinical response, and 60.0% (n = 6) achieved clinical remission based on Harvey-Bradshaw Index. Endoscopic improvement occurred in 54.5% (n = 6), endoscopic remission in 18.2% (n = 2), and endoscopic healing in 18.2% (n = 2) of patients. Mean Simple Endoscopic Score in CD significantly improved from 13.6 ± 5.2 to 6.5 ± 4.0 after treatment (P < .01). In patients treated with tofacitinib in combination with a biologic, no new safety signals were observed. Combination tofacitinib and a biologic was effective in achieving clinical and endoscopic improvement in some patients with severe, refractory CD, although a larger sample size is needed to further assess the efficacy and long-term safety of this treatment strategy.

What do we still need to learn on digitally assessed biomarkers?

What do we still need to learn on digitally assessed biomarkers?

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis.

Glycosylation is a common posttranslational modification, and glycan biosynthesis is regulated by a set of glycogenes. The role of transcription factors (TFs) in regulating the glycogenes and related glycosylation pathways is largely unknown. In this work, we performed data mining of TF–glycogene relationships from the Cistrome Cancer database (DB), which integrates chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-Seq data to constitute regulatory relationships. In total, we observed 22,654 potentially significant TF–glycogene relationships, which include interactions involving 526 unique TFs and 341 glycogenes that span 29 the Cancer Genome Atlas (TCGA) cancer types. Here, TF–glycogene interactions appeared in clusters or so-called communities, suggesting that changes in single TF expression during both health and disease may affect multiple carbohydrate structures. Upon applying the Fisher’s exact test along with glycogene pathway classification, we identified TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with Reactome DB knowledge provided an avenue to relate cell-signaling pathways to TFs and cellular glycosylation state. Whereas analysis results are presented for all 29 cancer types, specific focus is placed on human luminal and basal breast cancer disease progression. Overall, the article presents a computational approach to describe TF–glycogene relationships, the starting point for experimental system-wide validation.

P321 Cessation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn’s Disease: Individual Patient Data Meta-Analysis of 323 patients from 12 studies

Abstract Background The risk of relapse after anti-tumour necrosis factor [TNF] therapy cessation in Crohn’s disease [CD] patients with perianal fistulas is unclear. We aimed to assess the risk of relapse after anti-TNF cessation in a large cohort and to identify risk factors. Methods A systemic literature search was conducted to identify cohort studies reporting on the incidence of relapse after cessation of anti-TNF therapy in CD patients. Individual patient data [IPD] were requested from the original study cohorts. Inclusion criteria for IPD-meta-analysis (IPD-MA) included age ³ 18 years, perianal fistulizing CD as indication for start of anti-TNF therapy, minimal treatment duration ³3 doses, and remission of luminal and perianal CD at cessation of anti-TNF therapy. Primary outcome was CD relapse [either perianal or luminal]. Perianal fistula relapse was defined as recurrence of draining perianal fistula related to previous or new fistula tracks, or abscess. Luminal relapse was defined as a clinical, biochemical, endoscopic, or radiological relapse requiring treatment or dose optimization of IBD medication or surgery. In a secondary analysis, risk factors associated with relapse were assessed using multivariate logistic regression analysis. Results A total of 307 patients from 12 studies in 9 countries were included in this IPD-MA. The median duration of anti-TNF treatment prior to therapy cessation was 14 months [IQR 6.1 – 29.9]. In 272/307 patients [89%] anti-TNF therapy was started for active perianal fistula and in 34 [11%] for both active perianal fistula and luminal CD. 169 patients [55%] developed a relapse [either perianal or luminal] after a median follow-up after cessation of 25 months [IQR 12 – 54]. Overall cumulative incidence of relapse was 31% and 43% at 1 and 2 years after anti-TNF cessation. Risk factor for CD relapse include upper GI involvement (L4) [HR 1.9], whereas older age [A3 vs A1, HR 0.48] and continuation of concomitant immunomodulators [HR 0.62] were protective factors. For a subgroup of patients with active perianal fistula and in luminal remission at start of anti-TNF, the cumulative incidence relapse rates were 25% and 43% at 1 and 2 years. No considerable differences in risk factors were found within this subgroup regarding risk of recurrence. Of the 179 patients who relapsed, 104 were retreated with anti-TNF with a response rate of 85%. Conclusion According to this IPD-MA, approximately two-thirds of CD patients with perianal fistula remain in remission with regard to fistulizing and luminal disease during 2 years after cessation of anti-TNF therapy. Further risk stratification based on perianal fistula characteristics is required.

P165 Non-invasive biomarkers of type III collagen cross-linking reflects fibrolysis in patient with luminal CROHN’S DISEASE

Abstract Background Type III collagen of the interstitial matrix is highly expressed in fibrotic tissue of Crohn’s disease (CD) and suggested to undergo remodelling during the characteristic deep tissue inflammation. Periods of inflammatory flares and remission could thus be reflected by varying degrees of type III collagen degradation and formation in relation to fibrogenesis and resolution of fibrosis. The aim was to investigate the association between type III collagen remodelling and CD disease phenotypes based on the Montreal classification Methods 40 CD patients were endoscopically assessed according to the Montreal B classification (luminal or stricturing phenotype) and Harvey Bradshaw Index for clinical disease activity (&amp;lt;4 = inactive; &amp;gt;4 = active). Patients were stratified based on both the Montreal B classification and HBI scores. Biomarkers were assessed by ELISA: 1) CTX-III (cross-linked protease degraded fragments of type III collagen), PC3X (cross-linked type III collagen formation), 3) PRO-C3 (type III collagen formation), and 4) C3M (MMP-9 degradation fragments) Results Biomarker levels of CTX-III was significantly elevated in CD patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease and luminal- and clinically active- disease (p&amp;lt;0.01 and p&amp;lt;0.05, fig 1A). The levels of net fibrolysis of cross-linked type III collagen (CTX-III/PC3X) was significantly higher in patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease (p&amp;lt;0.001), luminal- and clinically active- disease (p&amp;lt;0.001), and patients with stricturing- and clinically active- disease (p&amp;lt;0.05, fig 1C). Significantly elevated levels of net type III collagen degradation (C3M/PRO-C3) were observed in patients with a luminal- and clinically active- disease compared to luminal- and clinically inactive- as well as stricturing- and clinically inactive- disease (p&amp;lt;0.05). Furthermore, net type III collagen degradation was elevated compared to patients with stricturing- and clinically active- disease (p&amp;lt;0.05, fig 1F). Biomarker levels of PC3X, C3M, and PRO-C3 were unable to differentiate between patient groupings (fig 1B, D, and E) Conclusion Proteolytic degradation of cross-linked type III collagen (CTX-III) reflecting resolution of fibrosis in CD patients with luminal disease, may be associated with a protective effect against fibrogenesis and progression to fibrostenosis. These data indicate differences in cross-linked and non-cross-linked type III collagen remodelling in CD patients, and their potential use for differentiating patient phenotypes and disease activity

P412 Effectiveness of ustekinumab in fistulising perianal Crohn′s disease refractory or intolerant to anti-TNF

Abstract Background The management of fistulising perianal Crohn′s disease (pCD) is a challenging problem for patients and physicians. New therapeutic alternatives are needed, particularly in anti-TNF refractory patients. Data regarding ustekinumab (UST) effectiveness in pCD are scarce. Our aim was to evaluate the clinical and radiologic effectiveness of UST in pCD patients refractory or intolerant to anti-TNF. Methods We conducted a multi-center retrospective observational study. All patients with anti-TNF refractory pCD treated with UST were evaluated. Demographic and clinical variables including concomitant drugs were registered. Clinical response was evaluated at 16 weeks and 12 months and was defined as a reduction of 50% of draining fistulas or a marked reduction in fistula drainage. In patients with a magnetic resonance imaging (MRI) before and after treatment initiation, radiologic response was defined according to Ng Score (healed, partial response, unchanged, deterioration). Results Thirty-two patients were included, 68.8% female, median age 44,11 (IQR 36.28-48.56). Median time from diagnosis to UST initiation was 12.94 years (IQR 7.52-19.52), 90.6% had received previously 2 anti-TNF (37.5% also vedolizumab) and 46.9% had more than 2 fistulas. In 22 patients (68.8%) pCD was the main indication for UST treatment while in the remaining 31.2% the main indication was luminal disease. Fifteen patients (46.9%) received antibiotics at the initiation of UST, 8 (25%) combo therapy with thiopurines and 21 (65.6%) had setons. Patients received a 6mg/kg IV dose and 87.5% received 90mg/8 week SQ for maintenance. Dose intensification was needed in 20 patients (62.5%) at a median of 13 months (IQR 8.00-19.5). Fifteen patients (46,9%) achieved clinical response at week 16, while 18/30 (60%) had clinical response at 12 months (three of them were in clinical remission). Nineteen patients (59,4%) had an MRI performed pre and post-treatment at a median of 15 months (IQR 10-19). 10/19 patients (52.6%) achieved a radiological response although no patient had all fistulas healed. In the multivariate analysis the only factor associated with clinical response at 12 months was the presence of setons at UST initiation (OR 7.0; IC95% 1.3-37.9). There were no factors significantly associated with radiological response or clinical response at week 16. Four patients experienced adverse effects (three perianal abscesses and one transient skin rash). Conclusion Ustekinumab was effective in achieving clinical and radiological response in anti-TNF-refractory fistulising pCD patients, although clinical and radiological remission was rare. Most patients needed UST dose intensification in this highly refractory cohort. Adverse effects were infrequent, mainly perianal abscesses.

Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study

ObjectiveNo studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. Patients and methodsRAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. ResultsEighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). ConclusionRapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

P245 Evaluation of quality of life in patients with perineal Crohn’s disease: a monocentric Tunisien study

Abstract Background Perianal manifestations of Crohn’s disease considerably affects the life quality of patients. This study aims to assess the quality of life of patients with perineal Crohn’s disease by using the SIBDQ (Short Inflammatory Bowel Disease Questionnaire) and to evaluate its correlation with the Perineal Disease Activity Index (PDAI). Methods We retrospectively reviewed the medical records of patients with perineal Crohn’s disease between January 2018 and December 2020. Patients with active luminal disease were not included in this study (Crohn’s Disease Activity Index (CDAI) &amp;gt; 150). All participants answered the SIBDQ. Active perineal disease was defined as a PDAI &amp;gt; 7. We studied the correlation between SIBDQ and PDAI. Patients were divided into 2 groups according to the duration of the disease greater or less than 5 years. SIBDQ and PDAI were compared between the 2 groups. Results We included 52 patients with a mean age of 37 years (range: 17–62 years). There were 34 males (65.4%) and 18 females (34.6%). Crohn’s disease has been diagnosed for 7.6 years in average (range 2–19 years). The PDAI varied from 1 to 15 (average=7) and the SIBDQ ranged from 11 to 66 (average= 41). The SIBDQ was inversely correlated to the PDAI with a Pearson’s correlation coefficient equal to -0.885 (p=0.01). Indeed, the SIBDQ score for patients with an active perineal disease was significantly lower than those with inactive one (28.3 ± 11.6 vs. 50.1 ± 7.7; p&amp;lt; 0.0001), which indicates a worse life quality. Comparing the 2 groups, there were no significant differences in terms of age, gender and PDAI. The SIBDQ was lower in patients who had the disease for more than 5 years compared to the other ones (38.3 ±15.6 vs.48.2 ± 7.5; p=0.003). Conclusion The quality of life for patients with perineal Crohn’s disease seems to be altered by both activeness and duration of the disease. The SIBDQ is a simple tool that helps physicians detect patients with poor life quality. Other studies are necessary to validate this questionnaire for the evaluation of the quality of life in patients with perineal Crohn’s disease.