Biological Therapy In Inflammatory Bowel Disease Research Articles

Systematic review with meta-analysis of the effectiveness of subcutaneous biologics versus intravenous biologics in inflammatory bowel diseases.

Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking. Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission. We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE ( Ovid ), EMBASE , PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675). Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08). Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding.

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease

Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

Alterations and Potential Applications of Gut Microbiota in Biological Therapy for Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that is closely associated with dysbiosis of the intestinal microbiota. Currently, biologic agents are the mainstream therapies for IBD. With the increasing incidence of IBD, limitations of biologic agents have gradually emerged during treatment. Recent studies have indicated that gut microbiota is highly correlated with the efficacy of biologic agents. This review focuses on alterations in both the components and metabolites of gut microbiota during biological therapy for IBD, systematically summarises the specific gut microbiota closely related to the clinical efficacy, and compares current predictive models for the efficacy of biologics, further highlighting the predictive value of intestinal microbiota. Based on the mechanistic analysis of faecal microbiota transplantation (FMT) and biologic agents, a new therapeutic strategy, comprising a combination of FMT and biologics, has been proposed as a promising treatment for IBD with improved efficacy.

P505 Smoking is associated with the development of adverse events of biological therapy in patients with Inflammatory Bowel Disease

Abstract Background Smoking has been associated with a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD) as well as with lower serum levels of anti-TNF agents and the development of antibodies against them. The aim of this study was to investigate the association between smoking and the appearance of adverse events (AEs) of biologics in patients with IBD. Methods Consecutive patients with IBD who receive biological therapy in a tertiary university hospital were included. The possible association of smoking with the presence of AEs was investigated, using a specially designed questionnaire including a wide range of AEs associated with biologics (infections, skin manifestations, musculoskeletal disorders, general symptoms, hypersensitivity reactions, thromboembololic events and psychological disorders). Results A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5–56) years, Crohn’s Disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] with completed questionnaire forms available were included in the study. There were 52 (35%) active smokers and 35 patients (24%) ex-smokers. The prevalence of all AEs was 86% in smokers 85% in ex-smokers and 78% in non-smokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes while taking biologics, both in the univariate (P = 0.02 and 0.008 respectively-Figure 1) and in the multivariate analysis (P = 0.02 and 0.007 respectively). These correlations were the same for the two diseases (CD & UC) except for arthralgias where there was a significant correlation only with CD (P = 0.02). There were no other significant associations between smoking and infections (P=0.77) or other AEs (P> 0.05). Conclusion Smoking is a predisposing factor for the development of AEs of biologics in patients with IBD. It could be suggested that quit of smoking may lead to the optimal benefit from the use of biologic therapy in IBD.

P504 Prospective analysis of micronutrient status and disease course in Inflammatory Bowel Disease

Abstract Background Biochemical deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium and zinc are common in patients with Inflammatory Bowel Disease (IBD) and some micronutrient deficiencies have been associated with adverse disease outcomes. This study describes the micronutrient status of a cohort of patients on biologic therapy for IBD and explores the relationship with disease activity. Methods Adult patients with IBD on biologic therapy attending the nurse specialist clinic had 16 serum micronutrients measured alongside routine biochemical screening for disease activity. 12 months of follow up data was collected using electronic patient records. Faecal calprotectin (FCP), albumin and CRP were measured at baseline - patients in whom these biomarkers were within normal range (i.e CRP <10mg/L, albumin >35g/L and FCP <250µg/g) were defined as being in biochemical remission. Disease relapse at follow-up was defined as escalation of maintenance therapy, use of corticosteroid, hospital admission or surgery. Relationships between micronutrient status and time to disease relapse were explored. Results 216 patients (42% female, median age 42, IQR: 30–57) were included. 128 patients had Crohn’s disease (CD). 97 patients were in biochemical remission at enrolment. 12.9% of the total cohort were zinc (Zn) deficient and 6.5% were selenium (Se) deficient. Deficiencies of folate, vitamin C, vitamin B12, vitamin B6 and vitamin D were also prevalent within the cohort. Se deficiency was associated with high CRP (p=.001), low albumin (p=.022), and raised FCP (p=.002) at baseline. Zn deficiency was associated with high CRP (p<.001) and low albumin (p<.001). During the 12 month follow up period, 22/216 patients suffered a disease relapse. Patients with low Zn or low Se levels at baseline were significantly more likely to relapse (p=.007 and p=.019 respectively). In subtype analysis, patients with CD and Zn deficiency were significantly more likely to relapse (p=.003) but this was not the case for UC patients. Patients with UC and Se deficiency were significantly more likely to relapse (p=.001) whereas those with CD were not. Conclusion Zn and Se biochemical deficiencies are common in our cohort of IBD patients on biologic therapy and are predictive of subsequent disease relapse. Whether these signals are causal or a secondary effect of disease activity needs to be explored in future intervention studies.

P040 Latent Tuberculosis Infection In A Patient With A Negative Interferon Gamma Release Assay Prior to Biologic Initiation for Crohn's Disease.

Biologic therapy has revolutionized the treatment of inflammatory bowel disease (IBD). Nevertheless, it is well known that biologics are associated with an increased risk of opportunistic infections such as tuberculosis (TB). Screening tests indicated before biologic initiation, namely interferon gamma release assay (IGRA) or tuberculin skin tests (TST), may be falsely negative. We present the case of a male with uncontrolled Crohn's disease (CD) with a negative screen for TB and how a high index of suspicion led to the discovery of latent tuberculosis infection (LTBI) and the appropriate deferment of biologic therapy. A 63-year-old South Asian male with coronary artery disease status post bypass graft, prostate cancer, diabetes and iron deficiency anemia presented with fatigue and dizziness for one week. He reported dark stools since immigration from Bangladesh two years ago. Vital signs and examination were unremarkable. Laboratory studies revealed a gradual decline in hemoglobin from 9 g/dL to 7 g/dL over several months. Esophagogastroduodenoscopy was unremarkable. Colonoscopy revealed friability, inflammation and erythema of the ileocecal valve and terminal ileum (TI) with minimal strictures. Biopsy was consistent with CD. He was started on azathioprine. Subsequent computed tomography (CT) enterography revealed thickened TI extending over a length of 9-10 centimeters. Due to disease severity and continued symptoms, he was referred to our tertiary care center where it was determined that he may benefit from biologic therapy. Patient underwent IGRA testing which was negative. Given his immigration from an endemic area and use of immunosuppressants, a CT of the chest was obtained which was significant for tree-in-bud opacities within the right upper lobe and multiple nodules. Transbronchial biopsy of the largest nodule showed necrotizing granulomatous inflammation. Bronchoalveolar lavage culture was positive for Mycobacterium tuberculosis. The patient was diagnosed with LTBI. Anti-tuberculin therapy was initiated, and biologic therapy was postponed. Biologic agents are increasingly utilized in the treatment of IBD. These agents confer an increased risk of infections i.e. TB and poor outcomes from severe disease. Patients with IBD are also susceptible to infections due to the immunosuppression imposed by the disease itself. The risk of TB varies with the biologic used with the highest relative risks associated with adalimumab and infliximab. Screening for LTBI is indicated in all patients for which biologics are being considered. The goal is to identify and treat individuals at high risk for TB reactivation. A thorough history and examination should be performed to assess pertinent signs and symptoms. While IGRA has demonstrated higher sensitivity and specificity compared to TST, immunosuppressed patients may have a false negative result as in our case. Combination testing may be the most sensitive approach though evidence is limited. In cases of high suspicion, imaging with plain radiograph or CT scan is a useful tool in supporting the diagnosis of LTBI and may show predominantly upper lobe cavitary disease. Biologic therapy for IBD should be deferred until at least one month of treatment for LTBI has been completed.

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease.

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1-10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10-15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti-tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti-tumor necrosis factors.

P401 Risk of severe COVID-19 outcomes associated with inflammatory bowel disease medications: Reassuring insights from the United Kingdom PREPARE-IBD multicentre cohort study

BackgroundDuring the early COVID-19 pandemic, the British Society of Gastroenterology (BSG) developed a risk stratification grid to inform the United Kingdom (UK) government regarding strict social isolation, termed “shielding”. This advised inflammatory bowel disease (IBD) patients thought to be most clinically vulnerable to SARS-CoV-2 infection or severe COVID-19 outcomes, to stay at home and minimize face to face contact, even with household members. Those considered at highest risk included recent commencement of combination biologic and immunomodulator therapy, prednisolone ≥20mg/day, presence of comorbidities, age ≥70 years or clinically active disease in those receiving immunosuppression. Mesalazine was not considered to increase risk. An acknowledged limitation was an absence of COVID-19 risk data. This study sought to identify patient or IBD medication-related factors associated with severe outcomes from COVID-19.MethodsPREPARE-IBD was a multi-centre observational United Kingdom (UK) cohort study including adult IBD patients (≥18 years) diagnosed with COVID-19 by PCR between 1st March 2020 and 31st August 2020. The primary outcome was severe COVID-19 defined as requirement for intensive care admission, invasive ventilation or death. We tested associations of severe outcomes with medications and other covariates using multiple logistic regression.Results211 patients were included from 60 UK centres. 56 of 211 patients (26.5%) met the primary outcome. Severe COVID-19 was more common in ulcerative colitis relative to Crohn’s disease patients (33.9% [37/109] vs. 18.6% [16/86], p=0.018). Shortness of breath, nausea and vomiting were more common with severe COVID-19 (p<0.001 and p=0.023 respectively). Multivariable analysis identified co-morbidities and age as associated with severe COVID-19 outcomes; odds ratio (OR [95% CI]) 1.68 (1.23-2.35) for each co-morbidity, and an OR 1.03 (1.00-1.05) with each successive year of age. Neither clinically active IBD (OR 0.58 [0.26-1.26]), non-white ethnicity (OR 1.98 [0.92-4.28]), nor prednisolone use (OR 2.42 [0.47-11.26]) were associated with increased risk. On multivariable analysis, mesalazine was associated with severe COVID-19 outcomes (OR 2.03 [1.01-4.12]). Univariable analysis identified biologics and thiopurines as protective (OR 0.38 [0.15-0.87] and 0.32 [0.092-0.86] respectively). On multivariable analysis no association of severe COVID-19 outcomes with thiopurine or biologic exposure was seen.ConclusionOur data provide reassurance for the continued evidence-based use of corticosteroids, immunomodulators and biologic therapies in IBD during the ongoing COVID-19 pandemic, and is consistent with an as yet unexplained association between mesalazine use and severe COVID-19 outcomes.

COVID-19 in IBD: The experience of a single tertiary IBD center

BackgroundItaly has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID‐19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. MethodsThis was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. Results1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001). ConclusionsOur data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.

S2307 COVID-19 in a Patient on Dual Biologic Therapy for Inflammatory Bowel Disease

INTRODUCTION: Preliminary data suggest that dual biologic therapy might be effective and safe in a subgroup of inflammatory bowel disease (IBD) patients. However, the safety and outcomes of dual biologic therapy in IBD with Coronavirus Disease 19 (COVID-19) is unknown. Here, we present a case of a Crohn’s disease (CD) patient on adalimumab (ADA) and ustekinumab (UST) combination therapy who developed COVID-19. CASE DESCRIPTION/METHODS: This is a 24-year-old man with fibrostenotic Crohn’s ileocolitis diagnosed at age 9. He had a secondary loss of response to infliximab despite dose escalation to 10 mg/kg in combination with methotrexate (MTX). He was then transitioned to ADA and dose was escalated to 40 mg weekly with MTX (subsequently self-discontinued MTX). He achieved clinical response but not remission with ADA. Magnetic resonance enterography showed active inflammation in the terminal ileum, distal sigmoid colon, and rectum (Image 1). A colonoscopy showed ulcerated and polypoid mucosa in the terminal ileum and at the ileocecal valve with narrowing and patchy, mild pan-colonic inflammation (Image 2A/B). ADA level was 17 mcg/mL without antibodies. Switching to a different biologic was recommended. The patient was hesitant about discontinuing ADA due to symptomatic improvement. After discussion of risks and benefits, it was decided to bridge with UST and continue ADA with a plan to eventually discontinue ADA if remission was achieved. He received standard intravenous UST loading followed by 90 mg subcutaneously every 8 weeks. Five months later, he tested positive for COVID-19 due to exposure to an infected individual. He was asymptomatic from a respiratory standpoint and his gastrointestinal (GI) symptoms were at baseline. He received a dose of UST 1 day prior to COVID-19 testing and last ADA was 1 week prior to testing. ADA was held and resumed 2 weeks after as he remained without fever, respiratory symptoms or new onset GI symptoms at 2 and 6 weeks after testing positive for COVID-19. DISCUSSION: This case describes a favorable outcome of a CD patient who tested positive for COVID-19 while on ADA and UST. Multiple series have demonstrated that biologic monotherapy is not associated with poor outcomes in COVID-19 infected IBD patients. Instead, corticosteroids, advanced age and co-morbidities are predictors of adverse outcomes. However, more data is needed on the safety of combination biologic therapy in the COVID-19 era.Image 1.: Magnetic resonance enterography (coronal T1 weighted image) showing wall thickening, edema and hyperenhancement involving the terminal ileum over a length of approximately 20 cm with associated vascular engorgement is present.Image 2.: Colonoscopy images showing polypoid stenotic ileoceal valve (A) and the terminal ileum showing ulcerations (B).

S3199 Cervical Cancer Screening and HPV Vaccine Awareness in Patients With IBD

INTRODUCTION: Studies have shown that patients with inflammatory bowel disease (IBD) have an increased risk of malignancy compared to the general population. In addition, cervical cancer screening in this high-risk group is often suboptimal. Human papillomavirus (HPV) vaccine is recommended, effective, and safe for all patients with IBD. This vaccine not only protects against cervical dysplasia in females, but it could also be effective in reducing the risk of anal, penile, and oral cancers in both genders. The aims of this study are to identify the rate of cervical cancer screening among patients with inflammatory bowel disease and to assess patients’ opinion regarding the HPV vaccine in addition to other vaccines currently recommended. METHODS: A self-designed anonymous survey was conducted on all adult (18–65) patients with IBD who presented for a routine clinic visit. The survey comprised of questions regarding gender, age, diagnosis, current IBD treatment, cervical smear test frequency, and vaccinations currently recommended for patients with IBD. Patients completed the survey in clinic under a physician’s supervision. RESULTS: Survey data from 18 IBD patients (mean age: 36 years, average IBD duration: 13 years) were analyzed. 50% of our patients were females and all of them were on immunomodulators or biologic therapy for IBD. Among surveyed women, 33% reported irregular cervical cancer screening and 33% did not remember when their previous testing was. Only 33% of women undergo testing regularly; 67% annually and 33% every 2 to 3 years. 55% of our patient population reported knowledge of HPV vaccine recommendation for IBD patients. CONCLUSION: Our study documents low awareness of HPV vaccine and suboptimal cervical testing in this outpatient population of IBD patients. A multidisciplinary approach to educate IBD patients about HPV vaccine and cervical testing recommendations is required to improve patients’ adherence and outcomes.Figure 1

Optimizing biologic therapy in IBD: how essential is therapeutic drug monitoring?

Proposed treatment targets for the management of inflammatory bowel disease (IBD) have moved beyond symptomatic improvement towards more objective end points, such as healing of the intestinal mucosa. This treat-to-target approach has been associated with improved disease outcomes such as diminished bowel damage, surgery and hospitalizations. Many patients with IBD require biologic therapy to achieve and maintain clinical and endoscopic remission, and antitumour necrosis factor antibodies remain the first-line biologic therapy in most areas of the world. Unfortunately, up to one-third of patients receiving this treatment are primary non-responders, and some patients that show an initial response can also lose response over time. Therapeutic drug monitoring (TDM) has been suggested as a useful tool to manage patients on antitumour necrosis factor treatment, including monitoring for dose escalation, de-escalation or to switch treatment. In this Perspective, we aim to summarize evidence and guidelines related to TDM in IBD management and also discuss potential strategies to optimize biologic treatment where TDM is not available.

Therapeutic drug monitoring in inflammatory bowel disease: for every patient and every drug?

The current review provides an updated overview on the role of therapeutic drug monitoring (TDM) of biological therapies in inflammatory bowel disease (IBD). We examine the data behind TDM for the antitumor necrosis factor agents, vedolizumab and ustekinumab, in patients with IBD. In addition, we discuss reactive vs. proactive TDM. There is a positive correlation between biologic drug concentrations and favorable therapeutic outcomes in IBD, although the majority of data refer to antitumor necrosis factor therapy. Reactive TDM has rationalized the management of patients with IBD with loss of response to biological therapy. Moreover, reactive TDM of infliximab has been proven to be more cost-effective when compared with empiric dose optimization. Preliminary data suggest that proactive TDM of infliximab and adalimumab applied in patients with clinical response/remission is associated with better therapeutic outcomes compared with standard of care (empiric treatment and/or reactive TDM). For all biologics in IBD, there is a positive correlation between drug concentrations and favorable therapeutic outcomes. Reactive TDM is the new standard of care for optimizing biologic therapies in IBD, whereas recent data suggest an important role of proactive TDM for optimizing antitumor necrosis factor therapy in IBD.

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ≥7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease.

The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

PGI35 - Systematic Literature Review of Real-World Evidence on Persistence, Switching, and Dose Escalation with Biologics in Inflammatory Bowel Disease in the United States

Biologic therapies have become mainstays of treatment for inflammatory bowel disease (IBD), with numerous treatment options now approved in the United States (US). However, evidence of real-world benefits with biologic therapies in IBD is limited. Medication persistence, switching, and dose escalation have been suggested as proxies for real-world safety and effectiveness. This study sought to review evidence on real-world patterns of persistence, discontinuation, switching, and dose escalation with biologics for treatment of IBD (Crohn’s disease [CD] and ulcerative colitis [UC]) among adults in the US. A systematic search and review of electronic medical databases (PubMed, Embase, and Cochrane; 2012 forward), conference abstracts (2016-2017), and bibliographies. Thirty-two studies, mostly retrospective, reported outcomes related to persistence (lack of discontinuations), switching, and/or dose escalations in IBD (20 in CD, 9 in UC, and 11 in IBD). Most studies examined biologics or anti–tumor necrosis factor (TNF) as a category, infliximab, adalimumab, or vedolizumab. Patient populations differed in terms of prior exposure to biologics and prior/concurrent nonbiologic treatments. Study design, follow-up times, and endpoint definitions also varied between studies. The results of all identified studies revealed that a high proportion of patients with IBD, CD, and UC discontinued biologic therapy. In most studies, 10%-37.5% of patients who discontinued index biologic switched to another biologic (range, 0%-100%). Additionally, 8%-44% of patients experienced dose escalations. The main reasons for treatment discontinuation were lack or loss of response and adverse events. Discontinuation rates increased by line of therapy and were higher with step-up therapy versus early initiation of anti-TNF (top-down approach). This review highlights high rates of discontinuations, nonpersistence, switching, and dose escalations with biologics in IBD in the US.

PWE-030 The Inflammatory Bowel Disease (IBD) Audit Programme at The Royal College of Physcians Reports on 10 Years of Achievements and Demonstrates Improvements in Care Of People with IBD

Introduction The IBD audit programme, first established in 2004 has conducted several rounds of audit. The programme’s aim is to improve the care of people with IBD by; facilitating the collection of key aspects of data on patient care and organisational services, analysing and disseminating the results, providing recommendations for improvements based on the key findings in the analyses. Methods Since 2006 the programme has facilitated up to 4 rounds of data collection on adults and children for inpatient care, organisation of IBD services and administration of biological therapies. We also collected data on patients experiences of care and the provision of care in primary care services. In 2015 the programme team hosted 8 regional workshops and proactively helped hospital IBD teams to develop action plans on key aspects of care that required improvements in their local areas. Results Over the 10 years of the programme’s work - a high level of participation in the audit has been achieved, >90% participation rate from IBD hospital teams across the UK. There have been many improvements in patient care, the most notable since 2006 to date, are a reduction in mortality during admissions, reduction in unplanned surgery, increased patient contact with an IBD nurse, improved rates of prescribing heparin and bone protection. From the biological therapies audit, results clearly demonstrate biological therapies for IBD are effective and safe treatments. Patterns of prescribing are changing with earlier use in patients with less severe disease suggesting doctors have become more familiar with the treatment. Despite the positive improvements, the most recent audit, reported in 2014, identified that there were still aspects of care requiring improvements including treatment of anaemia, access to dietetic support and management of people attending out patient care. Also, the two audits on patient experience between 2010 and 2012 showed no improvements in patient’s experiences of care. The 8 regional workshops hosted in 2015 across the UK proved to be a successful initiative. They were attended by 84 trusts and healthcare boards. 74% of delegates surveyed at 6 months agreed that these had helped them to improve their service. Conclusion 10 years of intensive working and engagement with the IBD community, the programme could not boast of its achievements without acknowledging the support of the community. However further and continued improvements in patient care for people with IBD are necessary. In 2016 the IBD audit programme will be transitioning to the UK IBD Registry. There will be a continued emphasis to help hospital teams to make continued improvements in the quality of care of people with IBD through a number of initiatives. Disclosure of Interest None Declared

Neurological disorders and inflammatory bowel diseases.

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.

Advances in the development of new biologics in inflammatory bowel disease.

Biologics have revolutionized the therapeutic approach in inflammatory bowel disease (IBD). Anti-tumor necrosis factor (anti-TNF) agents infliximab and adalimumab currently constitute the major biological therapy in IBD. Additional anti-TNFs such as golimumab and other new biologics are currently being developed for both anti-TNF-naïve and -resistant patients. These include anti-integrins (vedolizumab and etrolizumab), a JAK inhibitor (tofacitinib) and an anti-anti-interleukin (IL)-23 and IL-12 antibody (ustekinumab), among additional drugs in development. The following review discusses the indications, efficacy and safety issues for these novel medications.