anti-TNF Therapy In Patients Research Articles

Contrast-Enhanced Endoscopic Ultrasound Detects Early Therapy Response Following Anti-TNF Therapy in Patients with Ulcerative Colitis.

Though colonoscopy plays a crucial role in assessing active ulcerative colitis [aUC], its scope is limited to the mucosal surface. Endoscopic ultrasound [EUS] coupled with contrast-enhancement [dCEUS] can precisely quantify bowel wall thickness and microvascular circulation, potentially enabling the quantitative evaluation of inflammation. We conducted a prospective, longitudinal study to assess therapy response using dCEUS in aUC patients undergoing treatment with adalimumab [ADA] or infliximab [IFX]. Thirty ADA- and 15 IFX-treated aUC patients were examined at baseline and at 2, 6, and 14 weeks of therapy and 48 weeks of follow-up. Bowel wall thickness [BWT] was measured by EUS in the rectum. Vascularity was quantified by dCEUS using rise time [RT] and time to peak [TTP]. Therapy response was defined after 14 weeks using the Mayo Score. Patients with aUC displayed a mean BWT of 3.9 ± 0.9 mm. In case of response to ADA/IFX a significant reduction in BWT was observed after 2 weeks [p = 0.04], whereas non-responders displayed no significant changes. The TTP was notably accelerated at baseline and significantly normalized by week 2 in responders [p = 0.001], while non-responders exhibited no significant alterations [p = 0.9]. At week 2, the endoscopic Mayo score did not exhibit any changes, thus failing to predict treatment responses. dCEUS enables the early detection of therapy response in patients with aUC, which serves as a predictive marker for long-term clinical success. Therefore, dCEUS serves as a diagnostic tool for assessing the probability of future therapy success.

P731 Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A single-center experience

Abstract Background Discontinuation of anti–tumor necrosis factor alpha treatment (anti-TNFα) in patients with inflammatory bowel disease (IBD) poses a significant risk for relapse. The aim of this study is to analyze relapse rates and to possibly identify factors associated with relapse in IBD patients after treatment cessation with anti-TNFα. Methods This is a prospective study conducted at University Clinic of Gastroenterology in Albania from 2019-2022. IBD patients who discontinued biologic therapy with infliximab (IFX) or adalimumab (ADA) were included. All the patients discontinued therapy due to reimbursement issues. Demographic, clinical,laboratory and endoscopic data were collected for each patient. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis. Results A total of 52 IBD patients, mean age 50.8±14.7 years (46 UC and 6 CD), 25(48%) males, were included in the study. Mean follow-up was 29 months. 47.4% were treated with ADA and 51.5 % with IFX. The mean period of biologic therapy was 33.3 months for all patients. Upon treatment cessation, 55.8% of patients were in complete clinical remission, and 30.8% were in partial clinical remission. Cumulative relapse rates at 6, 12, 24 and 36 months were 23.9%, 39.1%, 44.2% and 69.7% respectively for all UC patients while 66.7% of CD patients relapsed within 6 months. The mean time to relapse was 13 months for UC and 5 months for CD patients. Among all IBD patients in complete clinical remission at the time of treatment discontinuation, the cumulative relapse rates at 6, 12, 24 and 36 months, were: 6.9%, 24.8%, 57.7%, and 58% respectively. Significantly higher cumulative relapse rates were found in patients with partial remission, the at the same time points: 37.5%, 50%, 75%, and 81.2% respectively (p=0.01). Multivariable Cox analysis revealed that the only factor associated with lower risk of relapse was mucosal healing (vs nonmucosal healing: HR, 0.322; 95% CI, 1.26 to 6.677; p=0.012). Conclusion The majority of IBD patients relapsed within 3 years after anti TNFα discontinuation, Mucosal healing was the only factor associated with a lower risk of relapse. These results emphasise the crucial role of mucosal healing in guiding treatment decisions for IBD patients.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

BackgroundDespite research, there are still controversial areas in the management of Crohn’s disease (CD).ObjectiveTo establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.MethodsClinical controversies...

Size Matters! Anti-HBs Titer and HBV Reactivation During Anti-TNF Therapy.

We and others have previously described that hepatitis B surface antibody (anti-HBs) seems to protect against clinically significant HBV reactivation in cohort studies of patients undergoing anti-tumor necrosis factor (TNF) therapy. However, there were too few cases of HBV reactivation within cohort studies to assess the role of anti-HBs titer on reactivation. The purpose of this study was to systematically review the correlation between anti-HBs titer and the degree of clinically relevant HBV reactivation in patients undergoing anti-TNF therapy. We systemically reviewed all studies discussing anti-TNF therapy in patients with resolved HBV infection, defined as hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive. We identified a total of 48 cases of reactivation from 5 cohort studies and 10 case reports or case series; 21 were anti-HBs negative, 7 were only reported as anti-HBs positive, 16 were anti-HBs positive with titer below 100, and 4 were anti-HBs positive with titer above 100. HBsAg sero-reversion was dominantly seen in patients with negative, low and/or declining anti-HBs titers. There was a significant trend toward less clinically relevant form of reactivation with increase in baseline anti-HBs titer (p = 0.022). Anti-HBs titers greater than 100 iU/L protect against clinically relevant HBV reactivation, while patients with low anti-HBs titers or negative anti-HBs had more clinically relevant HBV reactivation and higher rates of HBsAg sero-reversion. This suggests the importance of baseline quantitative anti-HBs prior to starting anti-TNF therapy and consideration vaccination for boosting anti-HBs titers prior to and/or during therapy.

Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.

This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-tumour necrosis factor [anti-TNF] therapy in patients with ulcerative colitis [UC] or Crohn's disease [CD]. TREM-1 whole blood gene expression was analysed by RNA sequencing in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]. TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.48], endoscopic remission [p = 0.53], clinical response [p = 0.58], or clinical remission [p = 0.79] at Week 8, or clinical response [p = 0.60] at Week 52. However, an association was observed with endoscopic response [p = 0.01], endoscopic remission [p = 0.048], and clinical remission [p = 0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p = 0.56], endoscopic remission [p = 0.33], clinical response [p = 0.07], or clinical remission [p = 0.65] at Week 12, or endoscopic response [p = 0.61], endoscopic remission [p = 0.51], clinical response [p = 0.62], or clinical remission [p = 0.97] at Week 56. Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with inflammatory bowel disease. NCT02065622; NCT02065570.

Association of MICA and NKG2D genetic variants with disease susceptibility and outcome of anti-TNF therapy in patients with axial spondyloarthritis.

The disruption of the NKG2D-MICA axis can induce an enhanced immune response and promote autoimmune processes during axial spondyloarthritis (axSpA) pathogenesis. We aimed to investigate potential relationships between selected single nucleotide polymorphisms within the MICA and NKG2D genes and disease susceptibility and clinical parameters in axSpA patients treated with TNF inhibitors. Genotyping of MICA rs1051792 and NKG2D rs1154831, rs1049174, and rs2255336 was performed in 163 axSpA patients and 234 healthy controls using a real-time PCR method. MICA rs1051792 A allele was more common in patients than in controls (p<0.0001). Patients with the AA genotype showed greater disease activity score (BASDAI) after three (p=4×10-4) and six (p=0.032) months of treatment compared to G carriers. After three months of therapy with anti-TNFs, the MICA AA homozygosity occurred more often in non-responsive or moderately responsive patients than good responders with the same genotype (p=1×10-4). Additionally, patients bearing the NKG2D rs1154831 CC genotype demonstrated lower BASDAI scores (p=0.035) and were significantly more common among subjects with a good outcome (p=0.004) after six months of treatment. These results suggest that MICA and NKG2D gene polymorphisms may be biomarkers associated with disease susceptibility and clinical outcomes after anti-TNF therapy in axSpA patients and imply a rather less favourable effect of the MICA A and NKG2D G genetic variants.

Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

Suboptimal response to tumor necrosis factor antagonists in inflammatory bowel disease in Latin America: EXPLORE LATAM study

ObjectiveData on anti-tumor necrosis factor (anti-TNF) treatment and suboptimal response (SOR) among patients with inflammatory bowel diseases (IBD) in Latin America (LATAM) are scarce. This study evaluated the incidence and indicators of SOR to anti-TNF therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) from Argentina, Colombia and Mexico. Patients and methodsWe performed retrospective analysis of data from LATAM patients of the EXPLORE study (NCT03090139) including adult patients with IBD who initiated anti-TNF therapy between March 2010 to March 2015. The cumulative incidence of SOR to first-line anti-TNF therapy was assessed. A physician survey to assess barriers to anti-TNF therapies was also carried out. ResultsWe included 185 IBD patients (UC/CD: 99/86) treated with first-line anti-TNF from Argentina (38 UC; 40 CD), Colombia (21 UC; 25 CD) and Mexico (40 UC; 21 CD). 36.4% of patients with UC and 46.5% of patients with CD experienced SOR to anti-TNF therapy during the median (interquartile range) observational period: 49.0 months (37.2–60.1) in UC, and 50.0 months (40.9–60.1) in CD. The most common indicator of SOR among patients was augmentation of non-biologic therapy (UC: 41.7%; CD: 35.0%). Affordability and late referral to IBD specialist care centers were the most common barriers to anti-TNF therapies. ConclusionsSOR to anti-TNF therapy was common in LATAM IBD patients, where augmentation with non-biologic therapy represented the most frequent indicator of SOR across indications. Our findings contribute to the current evidence on the unmet needs associated with anti-TNF in LATAM.

NEW ONSET OF INFLAMMATORY BOWEL DISEASE IN A PATIENT WITH EOSINOPHILIC ESOPHAGITIS: 10-YEAR CONSTELLATION OF AUTOIMMUNE GASTROINTESTINAL DISORDERS

Abstract INTRODUCTION Inflammatory bowel disease (IBD) is well known for concurrent immune-mediated disorders such as eosinophilic esophagitis, psoriasis, and rheumatoid arthritis.(1) For the past two decades, we are seeing an increased occurrence of eosinophilic esophagitis (EoE) in long standing IBD patients (2) (3) (4), but the question has arisen as to new onset IBD in chronic EoE patients. One study that involved 4814 patients demonstrated that the prevalence of eosinophilic esophagitis in IBD was 5 times higher compared to general population and EoE in IBD is 2 times higher than expected.(5) Multiple factors have been identified that may trigger the exact inflammatory response in IBD and EoE patients. Both diseases are associated with an exaggerated response to interleukins, especially IL-13 sharing cytokines and helper T cell mediated pathophysiology that is linked to disruption of the gastrointestinal tract barrier. (6) (7) CASE DESCRIPTION A 25-year-old healthy male presented back in 2012 with a history of three months of worsening dysphagia that resulted in 15-lb weight loss. Upper endoscopy showed esophagus with small caliber lumen, linear furrows, and thin concentric rings with microscopic evidence of eosinophilic esophagitis. Over the years he developed multiple episodes of persistent dysphagia, several endoscopies demonstrated pangastritis and duodenitis with a new pyloric and duodenal bulb stricture. Due to his remitting-relapsing course despite long-term medical treatment, patient underwent additional workup including an abdominal CT and upper endoscopy that showed worsening of the pyloric stricture that improved after balloon dilation. In 2020, the patient developed diarrhea, rectal bleeding, generalized abdominal pain and 21 lb weight loss despite medical treatment. Colonoscopy showed multiple erosions in the ileum and rectum not seen on previous studies. The biopsy indicated ulcerated mucosa with necrosis in the ileum and rectal area with mixed inflammatory infiltration with the presence of a non-caseating granuloma consistent with Chron’s disease. DISCUSSION It is unclear which disease manifest first or if it is a clustering and co-occurrence of diseases. The fact that both diseases share the same pathogenetic mechanism with overexpression of mucosal interleukin-13 (IL-13) causing loss of functionality of the gastrointestinal barrier could explain symptoms observed on both. Many studies demonstrated that IBD was diagnosed before EoE in almost 2/3 of the cases. The association of EoE-IBD is found significantly more in males and occurs at a younger age compared to IBD alone. Further studies will be needed in order to confirm the co-occurrence of diseases because of the increased risk of IBD-related complications and higher chance of requiring systemic corticosteroids and anti-TNF therapy in patients who have coexisting EoE-IBD.

Retreatment with anti-tumor necrosis factor therapy in combination with an immunomodulator for recurrence of Crohn's disease after ileocecal resection results in prolonged continuation as compared to anti-tumor necrosis factor monotherapy.

A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence. A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs. >1 anti-TNF agents. In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs. >1 anti-TNF agents (P = 0.88). Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure.

P37 A rare cause of autoimmune hepatitis secondary to a biological therapy

P37 A rare cause of autoimmune hepatitis secondary to a biological therapy

Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn's Disease.

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial

Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. Netherlands Organisation for Health Research and Development and Broad Medical Research Program.

Tumor Necrosis Factor Alpha -308G/A Gene Polymorphisms Combined with Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio Predicts the Efficacy and Safety of Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis Arthritis.

Background: TNF-α has been reported to be closely associated with autoimmune inflammatory diseases. This study aims to investigate the role of TNF-α -308(rs1800629) G/A gene polymorphisms as well as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the efficacy and safety of TNF inhibitors (TNFi) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriasis arthritis (PsA). Methods: A total of 515 subjects (181 AS, 144 RA, 48 PsA, 10 hyperbilirubinemia, 10 hyperlipidemia and 122 healthy control) were recruited in this study. The accuracy of RT-PCR methods for identifying individual TNF-α -308 genotypes was assessed using sequencing as the gold standard. Baseline NLR and PLR of patients with AS, RA and PsA and healthy controls (HC) were calculated and compared. Meanwhile, differences between responders and non-responders to TNFi treatment as well as between individuals with and without adverse effects (AE) among responders were compared. Results: The RT-PCR method is stable and reliable for TNF-α -308G/A gene polymorphism analysis, independent of sample status. The GG genotype was overwhelmingly represented, with relatively few GA genotype, whilst the AA genotype was not detected in this study. There was no observed association between TNF-α-308G/A polymorphism and susceptibility in AS, RA or PsA patients. Patients with AS, RA, and PsA had a higher NLR, compared to the HC group. Apart from PsA patients, AS and RA patients had a higher PLR, compared to the HC group. NLR was positively correlated with PLR. Furthermore, a lack of response was more frequently observed in AS and RA patients that carrying the GA genotype than the GG genotype. AS and RA patients with AE had higher NLR and PLR, compared with the non-AE group. Conclusion: Our study preliminarily shown that combining TNF-α -308G/A polymorphisms with NLR and PLR can predict the responsiveness and safety of anti-TNF therapy in patients with AS or RA.

P339 Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with Inflammatory Bowel Disease

Abstract Background The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. Methods Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The cut off of therapeutic TLs for both IFX and ADAs was, 5μg/ml. For anti-drug antibodies the cut off of, 10 AU/ml for IFX and, 3 AU/ml for ADA (as positivity of anti-drug antibodies was defined) was applied. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. Results A total of, 102 IBD patients [mean age (SD), 43.4 (13.8) years, females, 40 (39%), Crohn’s Disease, 85 (84%), under IFX, 50 (49%), under combination therapy with immunomodulator, 36 (35%), median duration of treatment (IQR), 33 (21–81.8) months] were included. Among them, 53 (52%) were ANA positive with, 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity (ANA greater than, 1:80) was found to be correlated with age (P=0.008), female gender (P=0.03), duration of treatment (P=0.06), arthralgias (P=0.04) and TLs (P=0.007). In multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P=0.04 and P=0.003 respectively). Studying separately IFX and ADA treated patients, the median IFX TLs of ANA(+) group (N=28) was, 3.51 (1.2–7.12) μg/ml significantly lower than the median IFX TLs of ANA(-) group [7.38 (4.83–10.3) μg/ml, N=22], P=0.017. The median antibodies to IFX of ANA(+) group was, 2.65 (2.4–3.24) AU/ml, significantly higher than the median antibodies to IFX of ANA(-) group [2.53 (2.11–2.83) AU/ml, P=0.03]. Regarding ADA treated patients, the median TLs of ANA(+) and ANA(-) group was, 7.33 (2.03–9.85) VS, 9.32 (6.17–10.05) μg/m (P=0.14), while antibodies to ADA in ANA(+) and ANA(-) group was, 1.42 (1.40–1.43) VS, 1.41 (1.40–1.43) AU/ml (P=0.52). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. Conclusion In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs, more remarkably with IFX TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

Impact analysis of expanding anti-TNF therapy for Crohn's disease.

Aim: To estimate the impact of universal anti-TNF therapy in patients with moderate-to-severe Crohn's disease. Materials & methods: Developed a population-level Markov model to estimate the impact on health outcomes and medical expenditures of expanding anti-TNF therapy use versus current treatment practices. Results: Reductions in deaths (2600), hip fractures (980), major adverse cardiac events (2700) and patient out-of-pocket medical spending (2%) over 5 years. Total societal costs would be US$22,100 higher per patient per year, primarily due to the high cost of anti-TNF therapy. Conclusion: Expanding anti-TNF therapy use among US adult patients with moderate-to-severe Crohn's disease would reduce morbidity and mortality, decrease disease-related medical costs and increase treatment costs compared with current practice. Despite the higher costs, this approach could substantially benefit patients.

Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease.

The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. InIBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn's Disease: A Pilot Study.

Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn's disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P < .001, P < .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3±8.7 kPa vs 15.3±4.7 kPa; P = .022) and bowel wall thickness (8.5±2.3mm vs 6.9±1.5mm; P = .027) in the nonresponse group were significantly higher than in the response group. This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

Fecal Microbiome Changes and Specific Anti-Bacterial Response in Patients with IBD during Anti-TNF Therapy.

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn’s disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).

P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease

Abstract Background The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD). Methods A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed. Results We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1. In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05). Conclusion The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.