Treatment Of Inflammatory Bowel Disease Patients Research Articles

Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients

Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

Outcomes of Treatment for Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease Receiving Biologic Therapy.

Treatment for latent tuberculosis infection (LTBI) is of particular concern in patients with inflammatory bowel disease (IBD) initiating biologic therapies to prevent tuberculosis (TB) reactivation. This study aimed to evaluate the effectiveness of LTBI treatment in IBD patients receiving biologic therapy. There was a retrospective review of all IBD patients diagnosed with LTBI following a tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) and who received biologic therapy between 2002 and 2016. The primary outcome was tuberculosis reactivation after completion of LTBI treatment. Three-hundred twenty-nine IBD patients were identified, and 35 (27 Crohn's disease; 8 ulcerative colitis) met the study inclusion criteria. The mean age was 38.3 years, and 68.6% were male. The most common LTBI treatment regimen was isoniazid (INH) for 9 months (74%). Biologic therapies used were infliximab (40%), adalimumab (29%), vedolizumab (20%), and certolizumab pegol (11%). Combination therapy with an immunomodulator was administered in 57% of cases. The median time from initiation of LTBI treatment to biologics was 43 days. The mean duration of follow-up was 2.9 years. The estimated median annual risk of TB reactivation without treatment was 0.52% by a prediction formula. Only 1 patient taking adalimumab monotherapy developed reactivation of TB several years after completing 6 months of isoniazid therapy. The estimated TB reactivation rate was 0.98 cases per 100 patient-years of follow-up in our cohort. Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.

Therapeutic Drug Monitoring of the Biosimilar SB2 (RENFLEXIS™, Infliximab-abda) Using LabCorp Infliximab Assays for Drug Level and Anti-drug Antibodies

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab (IFX) concentration and anti-infliximab antibody (ADA) titer has helped physicians make informed clinical decisions in the management of inflammatory bowel disease (IBD). A TDM-based approach to treating IBD patients has been used to improve clinical efficacy of anti-TNF agents. The LabCorp IFX TDM test (drug and ADA levels) has been validated in peer-reviewed literature and is widely used by clinicians to help maximize treatment response. Recently approved by the FDA for treatment of IBD, RENFLEXIS (SB2, infliximab-abda) is a biosimilar of the originator infliximab (TNF alpha inhibitor). The aim of this study was to validate the LabCorp IFX TDM test for the quantification of serum SB2 concentrations and ADA. METHODS: To demonstrate ability to measure RENFLEXIS using the LabCorp IFX TDM test, SB2-specific immunoassays were developed. SB2 calibrators and SB2-conjugated key reagents were used to compare with IFX TDM kits. Analytical performance including accuracy, precision, spike and recovery, specificity and selectivity was assessed. Exogenous SB2 was spiked into donor serum to assess recovery using the IFX drug assay. 124 IFX-treated IBD patients were split-tested using SB2 and IFX drug and ADA assays to assess equivalency and interchangeability between the two methods. RESULTS: Both SB2 drug level and ADA showed excellent agreement to IFX drug level and ADA respectively. SB2 assay accuracy (<11% bias) and precision (<7% CV) were equivalent to IFX accuracy (<5% bias) and precision (<10% CV) across the measuring range of the assay. More importantly, spike and recovery of RENFLEXIS using the IFX drug assay was equivalent to the recovery of reference product IFX using the IFX drug assay. SB2 was spiked into the donor serum pool to generate 0.25, 0.5, 1.0, 2.0, 4.0, 5.0, 6.0, & 8.0 ug/mL targets. The same target concentrations were generated for IFX. Both sets of targets were read using the IFX drug assay. Percent recovery of SB2 ranged from 87% to 114%; IFX recovery was 83% to 113%. Average spike and recovery was 99% for both SB2 and IFX using the IFX drug assay. Both the SB2 drug assay and IFX drug assay were used to analyze 59 serum samples of IBD patients treated with reference product IFX. The calculated linear regression between the two methods was Y=1.11x-0.13 and r2=1.0. The SB2-specific anti-drug antibody assay performed essentially identically to the reference product IFX ADA assay in terms of precision (<10% CV), accuracy (<10% bias), linearity, drug tolerance and sensitivity. 65 ADA positive serum samples from IBD patients were tested using the SB2 ADA assay. Antibody titer values were compared. Linear regressions of Y=1.09x-8.7, r2=0.99 were obtained. CONCLUSION(S): This study demonstrates complete cross-reactivity of RENFLEXIS (infliximab-abda) in LabCorp IFX TDM assay. Healthcare providers can confidently use LabCorp IFX TDM test to monitor RENFLEXIS (infliximab-abda) serum drug levels and ADA titers in their patients.

Mechanistic Understanding of Herbal Therapy in Inflammatory Bowel Disease.

The incidence and prevalence of inflammatory bowel diseases (IBD), which comprise ulcerative colitis and Crohn's disease, are increasing dramatically worldwide. Immunomodulators and biological agents can help but cause severe side effects in long-term use. As such, complementary and alternative medicine, in particular herbal remedy, is becoming more and more popular in the treatment of IBD patients. Many natural compounds have been used in clinical trials and some have been proven promising in IBD treatment. To achieve a better understanding of herbal therapy, researchers focus on understanding the underlying mechanisms by using experimental rodent models. The mechanism of the pathogenesis of IBD is complex involving both environmental and genetic factors. IBD is considered as a consequence of impaired epithelial barrier function, gut microbiota dysbiosis, and aberrant immune response. Studies have demonstrated that herbal medicine can improve epithelial proliferation and barrier integrity, restore microbiota homeostasis, and suppress hyper-immune reaction. This review is to summarize current understanding of the molecular basis of herbal treatment of IBD at the levels of epithelial, microbial, and immune regulation.

P648 Clinical feasibility of dried blood sampling for infliximab in IBD patients

Therapeutic drug monitoring (TDM) is important to optimise outcome of infliximab (IFX) treatment in inflammatory bowel disease (IBD). Dried blood spot (DBS) sampling using capillary blood obtained via a finger prick could facilitate TDM, since patients can administer this finger prick themselves at any time and away from the hospital. We investigated the predictive performance and the feasibility of DBS for measuring IFX concentrations in IBD patients. We studied 40 adult IBD patients receiving IFX therapy according to standard guidelines. From each patient blood was obtained simultaneously via venepuncture and DBS via finger prick by a trained employee at 3 different time points (trough, peak, 3–5 weeks after infusion). One week before IFX infusion (time point 4), patients performed DBS at home and the sample was directly sent to Sanquin laboratories, Amsterdam, The Netherlands. The corresponding serum concentration for this time point was estimated using Bayesian pharmacokinetic analysis using the three samples obtained by venepuncture. Capillary blood was obtained by a microsampling device developed by Neoteryx™. Haematocrit (Hct) values of each individual patient were used to convert DBS eluate results to values which can be compared with (venous) serum concentrations. Spearman’s correlation coefficient was used to assess correlation and bias was calculated. Forty IBD patients were included with median [interquartile range] age: 41 [32–50], albumin: 43 mg/l [41–45], and CRP: 1.3 mg/l [0.4–4.4]. IFX concentrations obtained from the DBS method correlated strongly with serum results from the same patient for IFX trough- and mid-interval concentrations (Spearman correlation coefficient >0.88) and moderately for IFX peak concentrations (Spearman correlation coefficient = 0.69). IFX serum concentrations from the DBS performed at home showed strong correlation with the concentrations obtained by Bayesian analysis (Spearman correlation coefficient = 0.71). No structural bias was shown (Table 1). Concentration range and relative bias. Concentration range and relative bias. DBS via finger prick can be used for the assessment of serum IFX concentrations. More importantly, we showed the feasibility of using DBS via finger prick at home. This method greatly facilitates the use of TDM in the treatment of IBD patients using IFX.

Effects of IRW and IQW on Oxidative Stress and Gut Microbiota in Dextran Sodium Sulfate-Induced Colitis

Background/Aims: There are known links between inflammatory bowel disease (IBD) and changes in the microbiota of the gut and inflammation and oxidative stress. In this study, a colitis model induced by dextran sodium sulfate (DSS) in mice is used to evaluate whether the presence of bioactive peptides IRW (Ile-Arg-Trp) and IQW (Ile-Gln-Trp) peptides is advantageous. Methods: The mice were arbitrarily assigned to the following four groups: (i) control (untreated), (ii) dextran sodium sulfate (DSS) treated, (iii) IRW-DSS treated, and (iv) IQW-DSS treated. For 7 days, the control group subjects had unrestricted access to untreated drinking water, whereas the drinking water supplied to the subjects in the DSS, IRW-DSS, and IQW-DSS groups during this period consisted of 5% DSS solution. The colonic lesions were scored after hematoxylin and eosin staining. Serum antioxidant capacity was analyzed by 2,2’-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical cation decolorization test and the microbiota in the colonic contents were sequenced by HiSeq2500 PE250. Results: The presence of DSS reduced daily weight gain, enhanced histopathology scores, and inhibited antioxidant enzyme expression. Superoxide dismutase, catalase, and glutathione peroxidase activities in the DSS-induced colitis model were significantly enhanced (P < 0.05) in the presence of dietary IRW and IQW. Furthermore, the Simpson index was significantly increased (P < 0.05) in the presence of dietary IRW and IQW compared to the control group. IRW and IQW increased the abundance of Coprococcus_1, Ruminococcaceae_UCG-014, and Desulfovibrio compared to the control group and DSS group. Furthermore, IQW decreased the abundance of Bacteroides in relation to the control group, but increased Parabacteroides. In addition, IRW increased the level of Anaerotruncus, Oscillibacter, and Ruminiclostridium_9 compared to the control group. Conclusion: This study concludes that the presence of IRW or IQW can mitigate DSS-induced oxidative stress by improving the activities of antioxidant enzymes, increasing intestinal microbial diversity and enhancing the abundance of gut microbiota, which may help maintain the homeostasis of host health and microenvironment in a DSS-induced mouse model, thus providing a potential further treatment for IBD patients.

Patient Perceptions Regarding the Use of Biosimilars in Inflammatory Bowel Disease

Introduction: Inflammatory bowel disease (IBD) often requires treatment with immune modulating medications (biologics). Although biologic agents have been shown to have excellent efficacy in treating IBD patients, the substantial cost has become a barrier to treatment for many patients. Recently, biosimilar drugs have been developed. Many clinical trials have demonstrated similar efficacy of biosimilars compared to originator biologics in IBD patients. Patients' perception and knowledge regarding these drugs is not known. We surveyed IBD patients to assess perceptions and knowledge regarding biosimilar medications and willingness to switch from biologics to biosimilars.Table: Table. Characteristic DataMethods: 121 consecutive adult patients in a single outpatient gastroenterology clinic with a pre-existing diagnosis of IBD were surveyed between March and May 2017. Data was then compiled and analyzed. Patients were excluded if they were not able to read English. Results: The mean age of the survey participants was 37.8 ± 15.5 years. Sixty-three percent of the participants were male. Fifty-three patients (43.8%) carried a diagnosis of UC. Sixty-seven patients (55.3%) had Crohn's disease (CD). One patient was not sure of his/her diagnosis. Significantly more CD patients than UC were currently on infliximab or adalimumab (35 vs 16, p=0.014). Only 33 participants (27%) have heard of “biosimilar medications” prior to this study. Seventy-six percent of all participants were uncomfortable using a biosimilar medication that had not been tested in clinical trials specifically for UC or CD. 57% participants were uncomfortable exchanging their current medication for a biosimilar. 92% of all participants wanted to be informed prior to switching to a biosimilar medication. There was a statistically significant correlation between the number of years since diagnosis and the patient's comfort with switching to a biosimilar medication (r=0.203, p=0.027). Conclusion: By investigating patient perceptions and knowledge regarding biosimilars, we hope to better understand patients' level of comfort, preferences, and potential barriers to implementation. Most IBD patients were uncomfortable using a biosimilar that has not been evaluate in a clinical trial in IBD. Of interest, a longer time since diagnosis of CD was associated with increased comfort of switching from biologic to biosimilar. This information will help physicians form their approach to introducing and discussing these biosimilars with patients.Table: Table. Patient Pereceptions Regarding Biosimilar Medications

Clostridium difficile Infection in Inflammatory Bowel Disease Patients: Influence of Antibiotic Choice on Adverse Outcomes

Introduction: Inflammatory bowel disease (IBD) is an independent risk for developing Clostridium difficile infection (CDI), which often precipitates an IBD flare. The influence of CDI treatment on IBD outcomes is not well understood. We evaluated the outcomes of CDI treatment in IBD patients to identify factors associated with adverse outcomes. Methods: Data abstracted from patients with IBD and CDI from 2008 to 2013 included CDI severity and management as well as rates of subsequent CDI episodes, CDI-related hospitalizations, IBD flares and colectomy at 1 year. Severe CDI was defined as WBC >15,000/μL or serum creatinine ≥ 1.5 times baseline and severe complicated was defined as hypotension, shock, ileus, megacolon, bowel perforation, ICU admission or bowel resection for IBD management at the time of active CDI. Subsequent CDI episodes were defined as return of symptoms with a positive stool test after completing CDI therapy. IBD flares post-CDI were defined as symptom recurrence, exacerbation or persistence with negative stool CDI. Statistical analyses comprised of descriptive statistics and one-way ANOVA. Results: Overall, 137 IBD patients (median age, 46.4 years; 55% female) were included; 51% with ulcerative colitis, 46% with Crohn's disease & 3% with indeterminate colitis. Infections were classified as mild-moderate (71%), severe (14%) and severe complicated (15%). Table 1 shows CDI severity and outcomes by CDI treatment regimen. About 40% of CDI from each severity cohort was treated with metronidazole. Treatment with both vancomycin and metronidazole was the second most commonly used regimen for severe or severe complicated CDI. No significant difference was observed among the different CDI treatments and infection severity (p=0.27). Further, CDI treatment choice did not significantly influence the rate of subsequent CDI (p=0.56), CDI-related hospitalization (p=0.15), IBD flare (p=0.54), or colectomy (p=0.42) 1 year post-CDI.Table. CDI: Severity and Outcomes by Antibiotic RegimenConclusion: IBD patients with CDI were most commonly treated with only metronidazole for their infection. The type or combination of antibiotics to treat CDI in these patients did not influence the rate of adverse events of subsequent CDI, CDI-related hospitalization, IBD flares, or colectomy at 1 year follow-up. There was no relationship between CDI severity and type of antibiotic regimen among IBD patients. Prospective studies are needed to further elucidate optimal CDI management in this high-risk group.

Update on the Therapeutic Efficacy of Tregs in IBD: Thumbs up or Thumbs down?

Crohn's disease and ulcerative colitis, the 2 major forms of inflammatory bowel disease (IBD) in humans, arise in genetically predisposed individuals because of an abnormal immune response direct against constituents of the gut flora. Defects in counter-regulatory mechanisms are supposed to amplify and maintain the IBD-associated mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory pathways in the gut could contribute to halt the IBD-associated tissue-damaging immune response. Various suppressive T cell (Tregs) subsets have been characterized phenotypically and functionally and over the last decade, there has been enormous effort for optimizing the procedures for the in vitro expansion/generation of these cells for therapeutic purposes. Here we review the mechanisms of action and functional relevance of Tregs in the maintenance of gut inflammation and analyze the available data about the use of these cells in the treatment of IBD patients.

Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host’s immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation. On the contrary, specific parasite infections are well known to be directly linked to carcinogenesis. Whether a helminth infection interferes with the development of colitis-associated colon cancer (CAC) is not yet known. In the present study, we demonstrate that the treatment of mice with the intestinal helminth Heligmosomoides polygyrus at the onset of tumor progression in a mouse model of CAC does not alter tumor growth and distribution. In contrast, H. polygyrus infection in the early inflammatory phase of CAC strengthens the inflammatory response and significantly boosts tumor development. Here, H. polygyrus infection was accompanied by long-lasting alterations in the colonic immune cell compartment, with reduced frequencies of colonic CD8+ effector T cells. Moreover, H. polygyrus infection in the course of dextran sulfate sodium (DSS) mediated colitis significantly exacerbates intestinal inflammation by amplifying the release of colonic IL-6 and CXCL1. Thus, our findings indicate that the therapeutic application of helminths during CAC might have tumor-promoting effects and therefore should be well-considered.

Long-Term Clinical Outcomes After Switching from Remicade\xae to Biosimilar CT-P13 in Inflammatory Bowel Disease

BackgroundLimited data are available on long-term clinical outcomes regarding the switch from Remicade® to the infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD) patients.AimsTo investigate long-term efficacy, safety, pharmacokinetic profile, and immunogenicity.MethodsWe performed a single-center prospective observational cohort study following an elective switch from Remicade® to CT-P13 in IBD patients.ResultsEighty-three patients were included (57 Crohn’s disease, 24 ulcerative colitis, and 2 IBD unclassified), and 68 patients completed one-year follow-up. Disease activity (Harvey–Bradshaw Index and Simple Clinical Colitis Activity Index) as well as inflammatory markers (CRP, fecal calprotectin) did not change significantly during the 1-year follow-up. In total, 7 out of 83 patients (8%) demonstrated detectable antidrug antibodies during follow-up, and 5 out of 7 antidrug antibody titers were already detectable at baseline prior to switching. Six patients (7%) discontinued CT-P13 due to adverse events.ConclusionsFollowing a switch from Remicade® to CT-P13, 82% of IBD patients continued treatment through 1 year. Disease activity scores and inflammatory markers remained unchanged during follow-up, and no CT-P13-related serious adverse events occurred. These 1-year data suggest that switching to CT-P13 in Remicade®-treated IBD patients is safe and feasible.

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue.

Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions; studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD.

Su1875 - Outcomes of Treatment for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease Receiving Biologic Therapy

Background Treatment for latent tuberculosis infection (LTBI) is of particular concern in patients with inflammatory bowel disease (IBD) initiating biologic therapies to prevent tuberculosis (TB) reactivation. This study aimed to evaluate the effectiveness of LTBI treatment in IBD patients receiving biologic therapy. Methods There was a retrospective review of all IBD patients diagnosed with LTBI following a tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) and who received biologic therapy between 2002 and 2016. The primary outcome was tuberculosis reactivation after completion of LTBI treatment. Results Three-hundred twenty-nine IBD patients were identified, and 35 (27 Crohn's disease; 8 ulcerative colitis) met the study inclusion criteria. The mean age was 38.3 years, and 68.6% were male. The most common LTBI treatment regimen was isoniazid (INH) for 9 months (74%). Biologic therapies used were infliximab (40%), adalimumab (29%), vedolizumab (20%), and certolizumab pegol (11%). Combination therapy with an immunomodulator was administered in 57% of cases. The median time from initiation of LTBI treatment to biologics was 43 days. The mean duration of follow-up was 2.9 years. The estimated median annual risk of TB reactivation without treatment was 0.52% by a prediction formula. Only 1 patient taking adalimumab monotherapy developed reactivation of TB several years after completing 6 months of isoniazid therapy. The estimated TB reactivation rate was 0.98 cases per 100 patient-years of follow-up in our cohort. Conclusions Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.

P008 Common and different inflammatory features in inflammatory bowel disease and colon cancer

Background: The etiology of Inflammatory Bowel Disease (IBD) is complex and still, for the most part, obscure. Although the adaptive immune response has classically been considered to play a major role in the pathogenesis, there are evidence for involvement of tissue resident cells such as ILC, T gamma-delta and MAIT cells. The inflammatory response also plays an important role in CRC development. Since inflammation-associated tumorigenesis can rely on the interaction of pathogens and inflammatory cells, triggering the release of inflammatory cytokines and recruitment of other pro inflammatory cells, in this study we wanted to understand how in IBD treated patients, innate immune response can drive toward tumor evolution. Methods: The identification of tissue resident immune cells was performed by flow cytometry after isolation and digestion of fresh intestinal biopsies, evaluating the frequency and the effector functions of ILC1, ILC3, MAIT and gamma-delta T cells. We analyzed a total of 52 samples: IBD at onset (n=12), IBD after therapy with Infliximab and Adalinumab (n=13), CRC (n=21), and healthy donors (n=6). Results: IFN gamma-producing ILC1 accumulated in IBD patients at onset, after treatment and in CRC. As expected TNF alpha-producing ILC1 were more abundant in IBD at onset and CRC. ILC3 producing IL17 but not IL22 accumulated in treated IBD patients and CRC but not in IBD at onset. Gamma-delta T cells with a predominantly effector phenotype were increased in IBD and in CRC. In particular, in CRC patients both gamma-delta T cells subsets were present, while in IBD patients the Vdelta1 subpopulation was more represented at onset but the Vdelta2 subset in treated patients. IL17 producing Vdelta1 cells accumulated in CRC but not in both IBD groups. Finally, MAIT cells were more represented in both groups of IBD than in CRC. Conclusions: Our results, albeit preliminary, suggest that the innate immune system participates to gut inflammation and colorectal cancer, suggesting the intriguing possibility that certain inflammatory responses can be common to both pathologies and contribute to the development of chronic inflammation associated cancer.

Current practice and clinicians’ perception of medication non-adherence in patients with inflammatory bowel disease: A survey of 98 clinicians

AIMThe survey ascertains perceptions and describes current practice of clinicians regarding medication non-adherence in patients with Inflammatory Bowel Disease.METHODSGastroenterologists, trainees and inflammatory bowel disease (IBD) specialist nurses from the United Kingdom were invited to a web based survey collecting data on clinician demographics, patient volume and level of interest in IBD. Respondents were asked to estimate non-adherence levels and report use of screening tools and interventions to improve adherence.RESULTSNon-adherence was seen as an infrequent problem by 57% of 98 respondents. Levels of non-adherence were estimated lower than evidence suggests by 29% for mesalazine (5ASA), 26% for immunomodulators (IMM) and 21% for biologics (BIOL). Respondents reporting non-adherence as a frequent problem were more likely to report adherence levels in line with evidence (5ASA P < 0.001; IMM P = 0.012; BIOL P = 0.015). While 80% regarded screening as important only 25% screen regularly (40% of these with validated assessment tools). Respondents stated forgetfulness, beliefs about necessity of medication and not immediately apparent benefits as the main reasons for non-adherence. Patient counselling on benefits and risks of medication was a commonly used intervention.CONCLUSIONClinicians treating IBD patients frequently underestimate non-adherence and use of validated screening tools is infrequent. Most respondents identified the main factors associated with non-adherence in line with evidence and often counselled patients accordingly. Professional education should focus more on non-adherence practice to avoid adverse treatment outcomes associated with non-adherence.

Perceptions on the Surgical Treatment of Inflammatory Bowel Disease in Spain. Results of a National Survey

IntroductionThe incidence of inflammatory bowel disease (IBD) is increasing in Spain but there is little information on the availability of multidisciplinary care. This study aims to assess surgeon's opinions on the current situation of surgery for IBD in Spain. MethodsAn electronic closed survey was sent to members of the Spanish Association of Surgeons (AEC) from January to March 2015. This was a 52-item anonymised questionnaire with questions about how the treatment of IBD patients is organized in each center, the existence of specific units, the management strategy in IBD patients, and the opinion of colorectal, general and trainee surgeons about the surgical treatment of IBD in their center and in Spain. ResultsOne hundred and ninety-two surgeons responded. Most participants work in tertiary hospitals (45%), most of them from different hospitals, some from the same hospital. Only 50% of hospitals have multidisciplinary teams for IBD. The initial approach is laparoscopic in 56% of cases, and 80% of participants in centers with multidisciplinary teams consider the timing of surgery to be appropriate. The annual number of IBD surgeries in tertiary hospitals is higher than in secondary hospitals in ulcerative colitis (57% vs 24% 10–15 patients/year, P<.001) and Crohn's disease (68% vs 28% 3–5 patients/month, P<.001). Most centers operate less than 10 ulcerative colitis patients per year, even larger centers (67%) and they perform ≤3J-pouches/month (ulcerative colitis and other indications) (P<.001). Ninety-five percent of surgeons consider that centralization of complex cases in specialized units and the creation of national registries should be developed. The majority of participants (70%) believe that there is a deficit in research and educational activities in IBD surgery in Spain. ConclusionThis survey suggests that most Spanish hospitals have a low volume of IBD surgery, even large tertiary hospitals, and many centers do not have a multidisciplinary team dedicated to IBD patients. Most survey participants believe it is necessary to develop registries and increase training and research in IBD surgery in Spain.

Estado de la cirugía de la enfermedad inflamatoria en España. Resultado de una encuesta nacional

IntroductionThe incidence of inflammatory bowel disease (IBD) is increasing in Spain but there is little information on the availability of multidisciplinary care. This study aims to assess surgeon's opinions on the current situation of surgery for IBD in Spain. MethodsAn electronic closed survey was sent to members of the Spanish Association of Surgeons (AEC) from January to March 2015. This was a 52-item anonymised questionnaire with questions about how the treatment of IBD patients is organized in each centre, the existence of specific units, the management strategy in IBD patients, and the opinion of colorectal, general and trainee surgeons about the surgical treatment of IBD in their centre and in Spain. ResultsOne hundred and ninety-two surgeons responded. Most participants work in tertiary hospitals (45%), most of them from different hospitals, some from the same hospital. Only 50% of hospitals have multidisciplinary teams for IBD. The initial approach is laparoscopic in 56% of cases, and 80% of participants in centres with multidisciplinary teams consider the timing of surgery to be appropriate. The annual number of IBD surgeries in tertiary hospitals is higher than in secondary hospitals in ulcerative colitis (57 vs. 24% 10-15 patients/year, P<.001) and Crohn's disease (68 vs. 28% 3-5 patients/month, P<.001). Most centres operate less than 10 ulcerative colitis patients per year, even larger centres (67%) and they perform ≤3 J-pouches/month (ulcerative colitis and other indications) (P<.001). Ninety-five percent of surgeons consider that centralization of complex cases in specialized units and the creation of national registries should be developed. The majority of participants (70%) believe that there is a deficit in research and educational activities in IBD surgery in Spain. ConclusionThis survey suggests that most Spanish hospitals have a low volume of IBD surgery, even large tertiary hospitals, and many centres do not have a multidisciplinary team dedicated to IBD patients. Most survey participants believe it is necessary to develop registries and increase training and research in IBD surgery in Spain.

From bench to bedside: molecular imaging in inflammatory bowel diseases.

Standard structural imaging procedures such as endoscopy, ultrasonography, or MRI are an integral part of the rational management of patients with inflammatory bowel diseases (IBDs). There is nevertheless the need for further refined imaging approaches that are able to overcome the limitations of currently used formats. The advent of molecular imaging modalities that allow real-time visualization of cellular processes not only in the preclinical setting but also in clinical trials has demonstrated its ability to improve current therapeutic strategies. The purpose of this review is to present and discuss advancements in the field of molecular imaging approaches in the IBD field. Recent preclinical and clinical studies have addressed the applicability of molecular imaging for improving the differentiation between benign and malignant mucosal alterations, increasing the detection of dysplastic intestinal lesions, and predicting individual responses to biological therapies. Molecular imaging in IBD represents an exciting and evolving field that has the potential to impact on current diagnostic and therapeutic algorithms in the treatment of IBD patients by analyzing and visualizing the molecular mechanisms that drive mucosal inflammation. It might enable us to base individualized therapeutic decisions on preceded molecular level analysis by suitable imaging modalities.

New molecules in the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a disorder of unknown aetiology that provokes chronic inflammation of the gastrointestinal tract. Anti-tumor necrosis factor drugs have represented a major advance in the treatment of IBD patients in the last few years and also have a good safety profile. Nevertheless, these treatments are not effective in all patients and, in initial responders, there can be a loss of response in the long-term. Consequently, new treatments are needed for IBD, aimed at distinct therapeutic targets. In the last few years, new molecules have been incorporated into the therapeutic armamentarium of IBD patients. Golimumab is an anti-tumor necrosis factor monoclonal antibody with demonstrated effectiveness in the treatment of ulcerative colitis. The use of CT-P13 (biosimilar infliximab) has been approved in Europe for the same indications as the original infliximab. More recently, vedolizumab, an anti-α4β7 integrin monoclonal antibody, has been approved for the treatment of Crohn's disease and ulcerative colitis. A large number of molecules are currently under development, some of which will, in the future, broaden the therapeutic options available in the treatment of IBD patients. Finally, in the next few years, studies should aim to identify factors predictive of response to the distinct biological agents for IBD in order to allow personalized selection of the best therapeutic alternative for each patient.

PTU-074 Vedolizumab in Primary and Autoimmune Sclerosing Cholangitis Associated Inflammatory Bowel Disease Pre and Post Liver Transplantation: A Case Series

Introduction Vedolizumab has been recently licensed by NICE for the management of moderate to severe inflammatory bowel disease (IBD). Currently, no data is available on the efficacy or safety of this treatment in the context of autoimmune liver disease (AILD) associated IBD, especially in those post-liver transplantation (LT). Methods Case series from two UK, tertiary IBD centres. Patients with primary and autoimmune sclerosing cholangitis (PSC and AISC) associated IBD were identified from a prospectively kept database. Clinical activity was assessed using Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) at baseline and end of follow up (response: drop in HBI/SCCAI >3, remission: HBI Results We identified 10 patients with ulcerative colitis (UC) and AILD. The median age was 33 years (19, 57), with a follow up of 6 months (3, 13). There were 6 patients with PSC and 4 with AISC [5 (50%) postLT)]. Clinical and/or endoscopically [Mayo score: 2 (2,3)] active disease was the indication for vedolizumab initiation in all patients with 7 (70%) having failed antiTNFα therapy before. Concomitant medication included: Tacrolimus: 4 (40%), Prednisolone: 7 (70%), MMF: 2 (20%), Azathioprine: 2 (20%) and Mercaptopurine: 1 (10%). A clinical response was seen in 4/10 (40%) and one patient achieved clinical remission. Surgery was required for one patient during induction due to severe colitis. A drop in faecal calprotectin [667 (60, 1080) vs. 182 (20, 349), p = 0.06] and improvement in QoL were observed [5 (0, 13) vs. 13 (8, 16), p = 0.03]. There were no infectious or other identified adverse events associated to vedolizumab. Conclusion Vedolizumab appears to be a safe treatment in IBD patients with AILD pre- and post-LT and appears to have reasonable efficacy even for difficult-to-treat luminal disease. Disclosure of Interest None Declared