Inflammatory Bowel Disease Clinical

Abstract

Journal of Gastroenterology and HepatologyVolume 32, Issue S2 p. 121-154 Supplement ArticleFree Access Inflammatory Bowel Disease Clinical First published: 17 August 2017 https://doi.org/10.1111/jgh.13895Citations: 5AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Accelerated dosing of infliximab induction and endoscopic mucosal healing in patients with acute severe ulcerative colitis YK An1, CY Chen1, LS White1, M Howlett1, A Lord2 and G Radford-Smith1,2 1Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; 2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Introduction: Recent evidence has indicated that an accelerated infliximab dosing regimen may reduce early colectomy rates in patients with acute severe ulcerative colitis (ASUC). However, there are limited data on rates of mucosal healing in those who receive accelerated regimens compared with standard dosing. Achieving mucosal healing has been unequivocally associated with better clinical outcomes. Aim: To determine whether accelerated infliximab induction achieves higher rates of endoscopic mucosal healing than standard induction, and consequently reduces the need for early colectomy in patients with ASUC. Methods: We prospectively collected data on hospitalized patients who received infliximab for steroid-refractory ASUC at a large, metropolitan teaching hospital inflammatory bowel disease (IBD) unit from January 2014 to December 2016. Patients received standard dosing (SD) or accelerated dosing (AD) at the discretion of one of two treating IBD physicians. In this retrospective study, we analyzed patients with at least 6 months of follow-up. We compared outcomes of dosing regimens. Clinical data collected on admission, at induction, and 3 months and 6 months after infusion were analyzed. Endoscopic data and rates of colectomy were compared between the groups during induction and follow-up periods until May 2017 (median follow up period of 12 months). Mucosal healing was defined as a Mayo endoscopic sub-score ≤ 1. Results: We analyzed the outcome in 44 hospitalized patients with steroid-refractory ASUC who received infliximab induction therapy. Overall, 27 were male (61%), with a mean age of 33 years (IQR, 25–46.25 years). Median disease duration was 1 year (IQR, 0–5.5 years), and 14 patients (32%) were on immunomodulators at admission. Sixteen patients received SD over an induction period of 6 weeks, and 28 received AD over a median duration of 18 days (IQR, 2–35 days). Patients receiving AD had a higher proportion of severe baseline endoscopic findings (Mayo endoscopic sub-score, 3) compared with SD (57% vs 38%), and higher C-reactive protein (CRP) levels at admission (113 ± 89.3 vs 69.4 ± 69.6). At 6 months' follow-up, mucosal healing was achieved in 18 patients (64%) in the AD group compared with 7 patients (44%) for SD. Median time to mucosal healing was 68 days (IQR, 54.75–142.8 days). Those who achieved mucosal healing maintained mucosal healing at long-term follow-up endoscopy. The colectomy rate was similar in AD and SD groups (21% vs 19%) over the follow-up period. Median time to colectomy was 46 days (IQR, 2–365 days). Factors associated with poor mucosal healing at 6 months were high induction CRP (t, –2.26, P = 0.033) and CRP:albumin ratio (t, –2.20, P = 0.034). The administration of triple combination therapy (infliximab, immunomodulators, and aminosalicylates) was associated with both maintaining long-term mucosal healing (odds ratio [OR], 0.31; P = 0.065) and reducing colectomy rate (OR, 0.24; P = 0.089). Conclusions: In this preliminary study of patients with ASUC, accelerated infliximab induction was found to be safe and effective, in terms of improving both the rate of mucosal healing and the colectomy rate. Larger and prospective studies are needed in ASUC to determine which patients would benefit most from accelerated infliximab induction. Correlation of fecal calprotectin levels with Crohn's disease activity (SES-CD) S Baral, L Brett, S Stanley, E Khoo, L Huang, D Shukla and C McIvor Department of Gastroenterology, Logan Hospital, Brisbane, Queensland, Australia Background: The link between the Simple Endoscopic Score for Crohns Disease (SES-CD) and relevant biomarkers has been extensively studied since 2010 (Yamaguchi et al 2016, Gesces et al 2015, Schoepfer et al 2010). Biomarkers, such as fecal calprotectin (FC), C-reactive protein, and erythrocyte sedimentation rate, are frequently used as they are non-invasive and easily accessible, particularly in a public health system at capacity with regards to colonoscopy availability. While a positive correlation between FC and SES-CD scores has been established, the data regarding the correlation between total mucosal healing in Crohn's disease (CD) and FC, and the correlation between ileal CD and FC levels, are still wanting. Aim: This study aims to further contribute to the existing international data on the use of FC as a marker of disease activity in CD. Methods: A retrospective analysis of routinely collected clinical data was conducted in 129 patients with CD who had undergone a colonoscopy in 2015–2016. The records were reviewed for SES-CD, the Montreal classification of disease, histopathology biopsies, and relevant biomarkers (if obtained within 1 month of their colonoscopy). FC (μg/g) was further subcategorised into three groups: < 100, 100–300, and > 300. Results: Forty-four of the 129 patients had a recorded SES-CD score, with a mean of 4.89. Of those, 25 patients had an FC test completed within 1 month. The mean SES-CD score and FC was moderately positively correlated at 0.5554 (P < 0.05) (Figure 1). Figure 1Open in figure viewerPowerPoint Correlation of mean SES-CD score and fecal calprotectin level Conclusion: FC appears to be significantly correlated with SES-CD. Due to the relatively small number of patients in our study and the incomplete nature of retrospective data, a larger prospective study is currently being undertaken with the aim of confirming the preliminary outcomes reported here and obtaining a more significant analysis of the potential connection between CD phenotype, severity, and FC. The use of topical calcineurin inhibitors for pyoderma gangrenosum in inflammatory bowel disease: An Australian case series A Bloom1, P Varma1, P De Cruz2, M Sparrow3 and S Pianko1 1Department of Gastroenterology, Monash Health, Melbourne, Victoria, Australia; 2Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia; 3Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia Introduction: Pyoderma gangrenosum (PG) is rare cutaneous condition characterized by ulcerative lesions with neutrophilic infiltrates, which can be seen in patients with systemic diseases, including inflammatory bowel disease (IBD). Tacrolimus and pimecrolimus are calcineurin inhibitors (CNIs) that can be applied topically for the management of PG; however, to date there have only been small-scale cohort studies and small case series evaluating their efficacy. We present six cases of topical CNI use in patients with IBD and report their safety and efficacy in the management of PG. Methods: We reviewed six patients with IBD who were managed with either topical tacrolimus (0.03%–0.1%) or pimecrolimus (1%) for PG across three tertiary centres. Results: Our cases are summarized in Table 1. The cohort was predominantly female (83%), with a mean age of 32.8 years, with severe stricturing (50%) or fistulizing Crohn's disease (50%), including one patient who expressed both phenotypes. Overall, 67% of our cohort were anti-tumor necrosis factor (anti-TNF)-experienced and 83% had previous disease-related surgical resections. The mean time to first clinical response was 3.2 weeks (range, 1–8 weeks). The mean duration of treatment was 12.2 weeks, excluding one patient who is still in the seventh week of treatment. Complete resolution of the lesion was achieved in 83% of patients; however, there was recurrence in two patients at 2 weeks and 12 months, respectively. Response was recaptured in these two patients with CNI therapy at 1 week and 4 weeks, respectively. There were no documented side effects to either CNI. Table 1. Case details Case No Age, Gender CD vs UC Montreal Classification Year of PG Dx Previous PG Rx (Yes/No) Topical CNI Type Time to First Response Duration of Treatment Complete Resolution (Yes/No) 1 36 F CD A2,L2,B2P 2008 No Pimecrolimus 1 week 13 weeks Yes, but recurred at 12 months 2 36 F CD A2,L1,B1 2014 Yes Tacrolimus 4 weeks 18 weeks Yes 3 30 F CD A2, L3, B2 2015 Yes Tacrolimus 2 weeks 7th week ongoing Not to date 4 33 M CD A2, L2,B3P 2016 No Tacrolimus 2 weeks 4 weeks Yes, but recurred at 2 weeks 5 27 F CD A2, L3/4, B2/3P 2016 No Pimecrolimus 2 weeks 18 weeks Yes 6 35 F CD A2, L3, B3P 2016 No Pimecrolimus 8 weeks 8 weeks Yes CD = Crohn's disease; CNI = calcineurin inhibitor; Dx = diagnosis; UC = ulcerative colitis; PG = pyoderma gangrenosum; Rx = treatment. Conclusion: In our case series, topical therapy with tacrolimus or pimecrolimus appears to be a safe and effective option in the management of PG among both anti-TNF-experienced and -naïve patients with IBD. Treatment response was noted to be rapid and seen as early as Week 1. There are currently no recommendations on the optimal treatment formulation and duration of CNI therapy. Larger-scale studies are needed to confirm these findings and guide the use of topical CNI in clinical practice. Entyvio Lengthen Dose Interval Study (ELDIS): An audit of dose frequency versus remission W Chan1,2, G Collins1, D Hetzel3, S Jakobovits4, G Radford-Smith5, P Bampton6, G Moore7 and RW Leong1 1Concord Repatriation General Hospital, Sydney, New South Wales, Australia; 2Singapore General Hospital, Singapore; 3Royal Adelaide Hospital, Adelaide, South Australia, Australia; 4Alfred Hospital, Melbourne, Victoria, Australia; 5Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; 6Flinders Medical Centre, Adelaide, South Australia, Australia; 7Monash University, Melbourne, Victoria, Australia Background: Vedolizumab (VED), a gut-selective α4β7 integrin monoclonal antibody, is effective for induction and maintenance of remission in patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD).1-3 The recommended treatment schedule is infusion at Weeks 0, 2, and 6, then every 8 weeks thereafter. The GEMINI long-term safety (LTS) study was an open-label study that determined the safety of VED maintenance.4, 5 Enrolled participants received 4-weekly VED. Upon completion of the LTS study, subjects were switched to 8-weekly VED according to Pharmaceutical Benefits Scheme (PBS) requirements. The benefit of 4-weekly versus 8-weekly VED treatment is currently not known. Aim: To determine the proportion of participants who flared after switching from 4-weekly to 8-weekly VED. Methods: Study sites that recruited patients into the GEMINI LTS study were audited. An online survey was devised to collect data on the demographic, biochemical, and endoscopic findings related to flare. Descriptive statistics, Fisher exact test and univariate analysis were used. Results: There were 29 patients who extended from 4-weekly to 8-weekly VED; 16 patients had UC and 13 had CD. There were 18 male participants, and 20 non-smokers, seven ex-smokers, and two smokers. The mean age of the patients was 48.8 (± 13.3) years, and the mean duration of disease was 17.2 (± 8.3) years. The median duration until a flare was 2.8 (± 1.7) months. There were five patients (17.2%) who developed recurrence of inflammatory bowel disease (IBD) on switching from 4-weekly to 8-weekly treatment (4 UC, 1 CD). The risk of a flare did not differ according to the type of IBD (P = 0.16). On univariate analysis, there was no association between flare and age, sex, smoking status, duration of IBD, extent of UC, or location and behavior of CD. Conclusion: About one in seven participants flared when switched from 4-weekly to 8-weekly VED. There were no clinical predictors of flare. This is the first study to demonstrate that certain patients require more frequent dosing of VED than that approved on the PBS. Biomarker studies are warranted to identify which patients will benefit from more frequent dosing. References 1Sands BE, Feagan BG, Rutgeerts P, et al. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology 2014; 147: 618–27.e3. 2Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N. Engl. J. Med. 2013; 369: 711– 721. 3Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2013; 369: 699– 710. 4Loftus EV, Colombel JF, Feagan BG, et al. Long-term efficacy of vedolizumab for ulcerative colitis. J. Crohns Colitis 2017; 11: 400– 411. https://doi.org/10.1093/ecco-jcc/jjw177. 5Vermeire S, Loftus EV, Colombel JF, et al. Long-term efficacy of vedolizumab for Crohn's disease. J. Crohns Colitis 2017; 11: 412– 424. https://doi.org/10.1093/ecco-jcc/jjw176. Comparison of infusion reactions to infliximab and vedolizumab: A retrospective analysis W Chan1,2, G Collins1, E Lee3, A Mahmoud3 and R Leong1,3 1Concord Repatriation General Hospital, Sydney, New South Wales, Australia; 2Singapore General Hospital, Singapore; 3Macquarie University Hospital, Sydney, New South Wales, Australia Background: Infliximab (IFX) and vedolizumab (VDZ) are monoclonal antibodies targeting tumor necrosis factor-α and α4β7 integrin, respectively, and are indicated in the treatment of inflammatory bowel disease (IBD). Both are administered by intravenous infusion and may be associated with different types of infusion reactions. Aims: To compare the incidence of infusion reactions in adult patients with IBD receiving IFX and VDZ treatment and to identify when these infusion reactions happened. Methods: We performed a retrospective review of all IFX and VDZ infusions performed at Concord Repatriation General Hospital and Macquarie University Hospital, Sydney, from January 2012 through March 2017. Fisher exact test and receiver operating characteristics (ROC) curve analysis were used. Results: A total of 157 consecutive patients who received 1921 IFX infusions and 61 patients who received 509 VDZ infusions were evaluated. All patients received intravenous hydrocortisone before IFX and VDZ infusion. Most patients were on concurrent immunomodulators (azathioprine or methotrexate). The overall incidence of infusion reactions to IFX was 1.3% (25/1921 infusions), affecting 14.6% of patients (23/157); and the overall incidence of infusion reactions to VDZ was 0.2% (1/509), affecting 1.6% (1/61). Mild-to-moderate and severe acute reactions occurred in 1.2% (23/1921) and 0.1% (2/1921) of IFX infusions, respectively. One case of mild-to-moderate reaction happened in VDZ infusion, but no severe reactions were observed. Compared with VDZ, IFX was associated with more mild-to-moderate infusion reactions (such as rash, arthralgia, tachycardia, and diaphoresis) (P = 0.0425 per infusion, Table 1), whereas the difference for severe reaction (such as significant hypotension, and severe dyspnea) was not statistically significant. Based on ROC curve analysis (Figure 1), the optimal number of IFX infusions after which infusion reactions were less likely to happen was eight (P < 0.01) and that for VDZ was not statistically significant. Table 1. Fisher exact test for reactions (per infusion) Mild-to-moderate reactions None P IFX 23 1898 0.0425 VDZ 1 508 Severe reactions None P IFX 2 1919 Not significant VDZ 0 509 Figure 1Open in figure viewerPowerPoint ROC Curve for IFX infusion reaction Conclusion: IFX is associated with more mild-to-moderate infusion reactions compared with VDZ, suggesting that IFX is associated with more immunogenicity. A proposed model of care for regional and rural patients with complex inflammatory bowel disease WR Connell1, AL Fisher2, T Samyue1, K Burrell1, S Fry1 and L Connell1 1Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia; 2Bendigo Health, Bendigo, Victoria, Australia Background: The management of inflammatory bowel disease (IBD) is increasingly complex and specialized. Disparities in health care expertise and capacity may lead to variations in the delivery and effectiveness of medical and surgical care. Although comprehensive multidisciplinary IBD services have been established in many Australian metropolitan centers, access for rural and regional patients with complex disease is often restricted. Alternative models of care that support local specialists to deliver best-practice IBD management to country patients need to be developed. Methods: In 2015, a complex IBD service was established in Bendigo, a regional city that services a population of 300 000 from central and northern Victoria. This service was initially instigated for public patients with more severe forms of IBD, most of whom were receiving or being considered for biological drugs. A monthly clinic was held in the city for patients from the region, staffed by a local gastroenterologist and visiting IBD specialist. Patients attending the clinic were linked to a multidisciplinary metropolitan IBD service and received ongoing support from its affiliated IBD nurses, colorectal surgeons, and psychologists, where necessary. Improved access to infusion services was established in the region. The clinical outcomes of this experience were reviewed, and patient satisfaction surveys evaluated. Results: A total of 53 patients with moderately severe IBD have been managed by the service: 28 (52%) were female, 45 (85%) had Crohn's disease, and the median age was 41 years (range, 19–84 years). Twenty-three patients had been previously receiving biological therapy, and six others were commenced on this treatment. Thirteen patients required specialist surgical referral: three intestinal resections, one to subtotal colectomy and ileostomy, two closures of stoma, one repair of entero-cutaneous fistula, and six for EUA. There were 13 smokers and five ex-smokers. Twenty-four patients (48%) had significant mental illness, including anxiety (6), schizophrenia (1), depression (10), bipolar disorder (2), history of sexual abuse (2), ADHD (1), and low intellectual level (2). Ten patients (19%) resided in postcodes listed in the top 10% for social disadvantage in Victoria. Responders to patient surveys reported general satisfaction with the standard of care, convenience, disruption to work, understanding of disease, and access to IBD nursing and psychological support. Conclusions: This preliminary experience shows that a regional IBD clinic co-managed by a local gastroenterologist and visiting IBD specialist can be implemented to provide quality medical and person-centered care in a convenient location. Patients attending this clinic had high rates of disease complexity, biological therapy, need for surgery, social disadvantage, and psychological morbidity. As local gastroenterologists are increasingly up-skilled in IBD management, the service should eventually become autonomous. However, a pure biomedical model is inadequate to cater for all the patients' holistic needs, and access to multidisciplinary personnel is just as important as in metropolitan centers. Models of regional IBD care must therefore enshrine streamlined access to local psychosocial facilities and the support of a dedicated local IBD nurse, whose job is to supervise biological therapy systematically, educate patients, and provide a point of contact outside clinic hours. Ongoing links with a metropolitan IBD service remain essential for those patients who require urgent medical admission, specialist colorectal surgery, or advanced endoscopic therapy. Colectomy rates remain high in the era of rescue therapy for acute severe ulcerative colitis: A single-center experience G Cunningham, M MacIsaac, N Ding, P Spizzo, W Connell, E Wright, M Lust, S Brown and S Bell Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia Background: Salvage therapy for acute severe ulcerative colitis (ASUC) with either cyclosporine (CyA) or infliximab (IFX) is associated with an 80% short-term response rate in reported series. Delays in access to salvage therapy are associated with increased colectomy rates in rural patients. Real-world salvage therapy data are lacking, however. Aim: The primary aim of this study was to determine the colectomy rate for ASUC from a tertiary inflammatory bowel disease center over a 5-year period from 2012 to 2017. The secondary aims were to determine the risk of colectomy in rural versus metropolitan patients and to identify predictors of colectomy. Method: A retrospective audit was conducted of all patients admitted with ulcerative colitis (UC) at a tertiary center over a 5-year period from 2012 to 2017. All patients who received intravenous (IV) steroids, as a surrogate marker for ASUC, were included, as positivity for the Truelove Witts criteria was not routinely documented. Data collected included demographics, rural status, inpatient length of stay (LOS), duration of IV steroid treatment, type of rescue therapy used, time to colectomy, and Clostridium difficile (CD) status. Results: A total of 144 patients were recruited; 55% of patients were male and the mean age at presentation with ASUC was 36 years (IQR, 26–43 years). The majority of patients lived in a metropolitan area (68%). The median inpatient LOS was 6 days (IQR, 4–11 days), and the median duration of IV steroid treatment was 4 days (IQR, 3–6 days). A total of 59 patients (41%) received salvage therapy (IFX, n = 38, 64.4%; CyA, n = 18, 30.5%; and tacrolimus, n = 2, 3.4%). One patient received both IFX and CyA therapy. The overall colectomy rate was 14.6%. This decreased from 26.1% in 2012 to 13% in 2016. The colectomy rate in the rural cohort was higher than in the metropolitan cohort; however, it did not reach statistical significance (20.5% vs 12.2%, P = 0.22). There were no statistically significant differences in duration of IV steroids, LOS, or requirement for rescue therapy in the metropolitan versus rural cohorts (all P > 0.05). On univariable analysis, the colectomy rate was significantly higher in those patients who required rescue therapy compared with those who did not (25% vs 6%, P < 0.01). There were no differences in colectomy rates according to type of rescue therapy (IFX, 21% vs CyA, 30%, P = 0.5), duration of steroids (4.4 vs 4.6 days, P = 0.4), LOS (8.9 vs 9.2 days, P = 0.4), CD-positive versus CD-negative (16% vs 11%, P = 0.7), age at presentation (P = 0.2), or sex (P = 0.6). On multivariable logistic regression analysis, increased LOS was significantly associated with colectomy (odds ratio, 1.35; P < 0.01). Age at presentation, sex, CD status, need for rescue therapy, duration of IV steroids, and rural residential location were not significantly associated with risk of colectomy on multivariable logistic regression. Conclusions: Colectomy rates remain high in the era of salvage rescue therapy for ASUC but have decreased over the past 5 years. Increased length of stay was significantly associated with a greater risk of colectomy. In contrast to other Australian studies, we did not find a statistically significantly increased risk of colectomy in patients living in a rural area compared with patients living in a metropolitan area. This may have been due to small sample size. An alternative explanation is that patients are being transferred from rural centers in a timely manner due to greater awareness about the need for rapid assessment and transfer of ASUC cases, or to more favorable geographical and logistical transfer factors facilitating faster interhospital transfer. We did not find a significant difference in colectomy rates between patients treated with IFX versus CyA rescue therapy. Assessing access to investigations in inflammatory bowel disease (ACCID): Results from an international inflammatory bowel disease survey NS Ding1,2,3, B Yazdanian4, D Bettenworth5, I Cleynen6, NA Yassin2, A Armuzzi7, M Ferrante8, ES Zagorowicz9, J Mansfield10, J Gisbert11 and T Raine4 1Inflammatory Bowel Disease, St Vincent's Hospital, Melbourne, Victoria, Australia; 2Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK; 3Department of Surgery and Cancer, Imperial College London, London, UK; 4Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 5Department of Medicine B, University Hospital Münster, Münster, Germany; 6KU Leuven, Leuven, Belgium; 7Gastroenterology Unit, Complesso Integrato Columbus, Rome, Italy; 8Department of Gastroenterology, UZ Leuven, Leuven, Belgium; 9Department of Gastroenterology, The Maria Sklodowska Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland; 10Department of Gastroenterology, Royal Victoria Infirmary, Newcastle Upon Tyne, UK; 11Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain Introduction: In recent years, several new investigations to aid diagnosis and monitoring of inflammatory bowel disease (IBD) have become available. These include fecal calprotectin (FC), widely regarded as a surrogate for intestinal inflammatory activity, and therapeutic drug monitoring (TDM) for thiopurine metabolites and anti-TNF therapy. However, uptake and access have not been uniform. We aimed to assess barriers to access of these investigations. Methods: Questionnaires were distributed to delegates at the 11th Congress of the European Crohn's and Colitis Organisation. Analysis of responses was performed using R statistical software, including binomial linear regression analysis for potential barriers to access, including health economic data extracted from the World Health Organization Global Health Expenditure database (https://planner.smartabstract.com/ecc02017/submission/en/abstract/3800/content#). A total of 195 valid responses were obtained from 38 countries, with the third highest response rate from Australia (11; 6%). Results: Access and use varied between tests (Table 1), with near universal availability and use of FC. Access and use of anti-TNF TDM was lower, with better access to TDM for infliximab than for adalimumab (P = 0.0004). Thiopurine TDM was least widely available but was used at an intermediate level where available. There was heterogeneity and lack of consensus when responders were asked to identify situations where each investigation might be used. Access to all three investigations within Europe showed a significant east–west and north–south divide,1 while Australia had access to all three tests in 100% of responses. Factors affecting access to tests were further analyzed by binomial linear regression analysis, which showed that the strongest independent predictor of access to all three tests was health care spending per capita (Table 2). Among Australian responders, all 11 responders cited cost, while five (45%) cited speed of test result as a barrier to the use of anti-TNF TDM. FC was available to 92.3%, most using it at least weekly (80.3%). Access to anti-TNF TDM was less widespread (78.9%; P = 0.0002) and less heavily used (45.8% using at least weekly; P < 0.0001). Access to TDM for infliximab was better than for adalimumab (P = 0.0004). Thiopurine TDM was least widely available (67.7%; P = 0.0001 vs FC, P = 0.02 vs anti-TNF TDM) but was used at an intermediate level where available (56.5% reporting at least weekly usage; P < 0.01 vs both other groups). All Australian responders were able to access and use thiopurine TDM, but barriers to ordering the test remained, including costs for six (55%). There was heterogeneity and lack of consensus when asked to identify situations where each investigation might be used. Table 1. Availability and greater than weekly use of FC, anti-TNF TDM, and thiopurine TDM (%) Test Availability > Weekly use FC 92.3% 80.3% Anti-TNF TDM 78.9% (P = 0.0002 vs FC) 45.8% (P < 0.0001 vs FC) Thiopurine TDM 67.7% (P = 0.0001 vs FC; P = 0.02 vs anti-TNF TDM) 56.6% (P < 0.01 vs both other groups) Table 2. Multivariable analysis of predictors of test access Factor FC access (P) Anti-TNF TDM access (P) Thiopurine TDM access (P) Health care spending per capita 0.005 < 0.0001 < 0.0001 Academic center NS 0.03 0.02 Professional status NS NS NS IBD workload NS NS NS IBD experience NS NS NS Multivariable analysis showed that the strongest independent predictor of access to all three tests was health care spending per capita (P = 0.005 for FC; P < 0.0001 for both TDMs). Working in an academic center was an independent predictor of access to TDM (P = 0.03 for anti-TNF; P = 0.02 for thiopurine). Respondents were more likely to cite cost as a barrier to accessing anti-TNF TDM (30.8%) or FC (24.6%) than thiopurine TDM (12.3%; P < 0.0001 and 0.003). Conclusions: Investigations for the purpose of personalizing therapy have revolutionized