Background Patients with inflammatory bowel disease (IBD) face complex health tasks and decisions. Limited health literacy is a risk factor for poor health outcomes, but this has not been examined in IBD. This study aims to assess the role of health literacy for patients with IBD. Methods We prospectively enrolled adults with IBD receiving care from the Section of Gastroenterology at the Boston Medical Center. In-person, standardized questionnaires were administered to measure health literacy with the Newest Vital Sign, self-efficacy with the Medication Use and Self-Efficacy Scale, quality of life with the 10-question Short Inflammatory Bowel Disease Questionnaire, depression with the Patient-Reported Outcomes Measurement System Short Form, and clinical disease activity for patients with Crohn's disease with the Harvey-Bradshaw Index and for patients with ulcerative colitis with the Simple Clinical Colitis Activity Index (SCCAI). The relationships between health literacy and these variables were subsequently examined. Results Of 112 patients invited to participate, 99 enrolled and completed the interview. Limited health literacy was identified in 40% (n = 40) of patients. Patients with limited health literacy reported significantly worse overall health (P = 0.03) and more depressive symptoms (P = 0.01). Of the 56 patients with Crohn's disease, those with adequate health literacy were more likely to be in clinical remission (mean Harvey-Bradshaw Index score < 5), compared with those with limited health literacy (odds ratio, 4.15; 95% confidence interval, 1.37 to 13.45; P = 0.01). There was no significant association between health literacy and clinical disease activity (SCCAI) in patients with ulcerative colitis. Conclusions Limited health literacy is associated with lower ratings of subjective health and depression in IBD and more symptoms of active disease in patients with Crohn's disease.
Background Racial and socioeconomic disparities exist in the treatment and outcomes of children and adults with Crohn's disease (CD). This study investigated the impact of race and insurance status on emergency department (ED) evaluation and treatment among children with CD in the United States. Methods Data from the Pediatric Health Information System included ED visits between January 2007 and December 2013 for patients aged 21 years with a primary diagnosis of CD, or a secondary diagnosis of CD plus a primary CD-related diagnosis. Analyses were performed using mixed-effects logistic regression. Results Subjects included 2618 unique patients (black, 612 [23%]; white, 2006 [77%]) with 3779 visits from 38 hospitals, a median age of 14.0 4.0 years, and 50% male. White children had a higher median neighborhood income and were more likely to have private insurance (57% vs 30%; P < 0.001). Emergency department visits for privately insured patients had higher odds of complete blood count (odds ratio [OR], 1.43; 95% CI, 1.08-1.90) and C-reactive protein/erythrocyte sedimentation rate (OR, 1.39; 95% CI, 1.06-1.82) vs Medicaid insured. Visits for white children had higher odds of receiving antiemetics (OR, 1.52; 95% CI, 1.06-2.17) vs black children. The proportion of patients with repeat visits was greater for black children (33%) than white children (22%; P < 0.001) and greater for Medicaid-insured (27%) than privately insured patients (21%; P < 0.01). Conclusions This cross-sectional database study demonstrated that black children and those with Medicaid insurance made more ED visits and received somewhat fewer treatments, which may be explained by greater use of the ED for routine care. An opportunity exists for better outpatient management of children with IBD so that nonemergent problems are more effectively handled.
Background Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity. Methods Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the electronic medical record. RNA extraction and human transcriptome microarray were performed on noninflamed ileal margins from operative specimens. Clinical data and random forest were analyzed in R. Principal components analysis, hierarchical clustering, and pathway enrichment were performed in Partek. Results Sixty-five patients completed the study, and 5 were excluded from analysis due to extreme variability on whole transcriptome analysis. Unsupervised hierarchical clustering revealed that patients with an i0 Rutgeerts score generally segregated from all others. In anti-TNF-naive patients, unsupervised hierarchical clustering revealed complete segregation of patients with an i0 score. Reduced escalation in therapy and continued mucosal remission, consistent with indolent disease, were seen in the 4 years following surgery. Random forest identified 30 transcripts differentiating i0 patients from the other groups. Pathway enrichment highlighted toll-like receptor, NOD-like receptor, and TNF signaling. This transcriptome signature did not identify i0 anti-TNF-exposed patients. However, anti-TNF-exposed patients with indolent postoperative courses were found to have a transcriptome signature distinct from those with aggressive disease. Conclusions Anti-TNF-naive and -exposed patients have unique expression profiles at the time of surgery, which may offer predictive value in assessing the risk of nonrecurrence.
Background The infliximab biosimilar has entered daily inflammatory bowel disease (IBD) practice. However, real-life outcomes beyond 1 year after switching are scarce. We aimed to investigate the long-term drug survival, immunogenicity, and pharmacokinetics 2 years after switching to CT-P13 in IBD patients. Methods We performed a single-center prospective observational cohort study in all Remicade-treated IBD patients who previously switched to CT-P13. We systematically documented reasons for discontinuation, trough levels, and antidrug antibodies to infliximab (ADAs) at baseline, week 16, week 52, and week 104. Clinical and biochemical disease activity (HBI, SCCAI, CRP) and adverse events were registered. Results Eighty-three patients were enrolled, 57 had Crohn's disease, 24 had ulcerative colitis, and 2 were IBD-unclassified. At week 104, 55 of 83 (66%) patients remained on CT-P13, and 3 were lost to follow-up. Reasons for discontinuation were loss of response (n = 10), adverse events (n = 8), and disease remission (n = 7). ADAs were present in 5/83 patients at baseline (before switching), in 2 patients before week 52, and no subsequent ADAs were detected until week 104. Median trough levels and clinical and biochemical disease activity at baseline, week 16, week 52 and week 104 did not significantly change. Conclusion In a prospective cohort with >2-year follow-up, 66% of IBD patients continued CT-P13 after switching from Remicade. Two new cases with ADAs were observed in year 1, but subsequently no immunogenicity was detected. These results are reassuring and suggest that switching to CT-P13 does not impact long-term clinical outcomes.
Background Responders to induction treatment sustain continuous clinical response (CCR) through 1 year in about 50% of patients in PURSUIT-M trial with golimumab maintenance in ulcerative colitis (UC). This post hoc analysis of PURSUIT-M describes the 1-year clinical, endoscopic, quality of life (QoL), and biomarker and 4-year clinical outcome in patients with sustained response to golimumab therapy for UC. Methods We compared clinical, endoscopic, QoL, and calprotectin outcomes in CCR and non-CCR patients through 54 weeks in PURSUIT-M. Persistence on golimumab therapy and clinical response at 4 years was assessed for CCR and non-CCR patients. The relationship of colectomy with CCR status was determined. Results Among patients receiving golimumab maintenance, greater proportions of patients with vs without CCR at week 54 achieved clinical remission (67.1% vs 1.9%), corticosteroid-free remission (61.6% vs 1.9%), endoscopic remission (Mayo endoscopy score 0 [47.9% vs 1.3%]), and normal QoL (inflammatory bowel disease questionnaire score 170 [75.0% vs 24.4%]). CCR but not non-CCR patients maintained normalized calprotectin levels during maintenance. Among patients who entered the long-term extension study, a greater proportion of patients with vs without CCR maintained PGA 0 through week 216 (58% vs 42%). Colectomy was performed in 47 induction nonresponders and in 13 induction responders. None of the patients going onto colectomy achieved CCR through 54 weeks in PURSUIT-M. Conclusions Continuous clinical response is associated with favorable short- and long-term clinical, endoscopic, QoL, and biomarker responses that may result in changing the course of disease and may prevent colectomy in patients with moderate to severe UC treated with golimumab.
Background Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome. Methods Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (<80 kg body weight) or 100 mg (80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26. Results From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naive. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy. Conclusions Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. media content-type="brightcove" orientation portrait position="float
Background There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24. Methods In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula healing. Results A total of 667 children with Crohn's disease were recruited, with 85 (12.7%) patients diagnosed with fistulizing PCD. There were 27 of 52 (52%) children in whom pre-fourth infusion IFX levels were measured (mean age, 12.57 5.12 years). At week 24, 14 of 27 (52%) patients responded with healing/healed PCD, whereas the rest had ongoing active fistulizing disease. The median IFX pre-fourth dose level in the responders was 12.7 ug/mL, compared with 5.4 ug/mL in the active disease group (P = 0.02). There was a strong correlation between IFX levels and healing of fistulizing PCD at week 24 (r = 0.65; P < 0.001). The AUROC was 0.80 (95% confidence interval, 0.64-0.97; P = 0.007) for pre-fourth IFX level to predict response of fistulizing PCD at week 24, and a level of 12.7 ug/mL best predicted fistula healing. Conclusions Higher trough IFX levels are associated with healing of fistulizing perianal CD.
Background Thiopurine metabolite monitoring to proactively dose optimize to achieve therapeutic levels has not been used consistently, and it is unclear if this would lead to better outcomes. We aimed to compare 6-month outcomes between standard and optimized dosing strategies and define long-term predictors of thiopurine durability. Methods Two hundred sixteen pediatric IBD patients with at least 2 6-thioguanine nucleotide (6-TGN) levels were grouped for analysis by start dose: >2.5 mg/kg/day AZA (group 1) or <2.5 mg/kg/day (group 2) and further subgrouped depending on whether dosing was optimized to achieve 6-TGN >235 pmol/8 x 10(8) RBC. The metabolites, 6TGN and 6MMP, were univariate and multivariate analyses tested associations among metabolite levels, laboratory data, and the primary outcome of 6-month steroid-free clinical remission (SFR) (HBI 4 for CD; partial Mayo Score [pMS] 2 for UC). Thiopurine durability was measured using Kaplan Maier survival analysis. Results 6-MP, azathioprine, pediatrics, therapeutic drug monitoring, pediatrics were measured a median 59 (43-76) days after initiation of thiopurine. Both dosing strategies led to similar initial 6-TGN levels (group 1 = median 209 [IQR: 155-272] with 25% of patients >235; group 2 = 196 [139-274] with 29% >235). Steroid-free clinical remission was achieved in 74% of the 180 still on thiopurines at 6 months. Start dose was not associated with 6-month SFR73% in group 1 and 77% in group 2 within those on thiopurines at 6 months (P = 0.61). Fixed- and optimized-dosing subgroups had similar 6-month 6-TGN levels, SFR rate, and percentage 6-TGN > 235. Only 6-TGN level >235 at 6 months predicted thiopurine durability (3 years [1.7-7.7] vs 2.5 years [0.83-5]; log-rank P < 0.001), and this did not retain significant in a multivariate model. Initial dosing strategy, first 6-TGN level, 6-month SFR, 6MMP:6TGN ratio, and delta-MCV did not predict durability. The rate of adverse events was 22%. Conclusions Steroid-free clinical remission and 6-TGN levels at 6 months were no different between a standardized, fixed dosing strategy and a metabolite-driven, optimized dosing strategy.
Background Infliximab (IFX) discontinuation is not uncommon during the first year of treatment due to inadequate drug concentrations and anti-IFX antibodies (ATI). Both combination therapy and proactive therapeutic drug monitoring (pTDM) are used to decrease ATI and increase IFX durability. We proposed that monotherapy (Mono) is as effective as combination therapy (Combo) if the first maintenance infusion is dosed based on week 10 pTDM. Methods In a retrospective cohort of 83 patients with inflammatory bowel disease (IBD), we examined the frequency of IFX discontinuation, ATI, infusion reactions, and IFX concentrations during the first year of treatment in patients receiving week 10 pTDM-guided IFX monotherapy (Mono pTDM; n = 16) compared with patients on mono (n = 32) or combination therapy (n = 35) in whom TDM was introduced at or after week 14, per standard of care (SOC). Results The frequency of IFX discontinuation was lower with Mono pTDM compared with Mono SOC (P = 0.04) but did not differ with Combo SOC (P = 1). At first TDM, no patient in the pTDM strategy had ATI, vs 41% in Mono SOC (P = 0.002) and 6% in Combo SOC (P = 1). Of the 13 subjects with ATI in Mono SOC, 7 (47%) had ATI already at week 14. IFX trough concentrations with Mono pTDM were higher during maintenance compared with Mono SOC (9.5 vs 6.4 mu g/mL, P = 0.04) but not Combo SOC. Conclusions Infliximab durability did not differ between patients on IFX monotherapy dosed based on p-TDM and patients receiving combination therapy. In the absence of concomitant immunosuppression, proactive TDM may improve IFX durability by maintaining higher IFX concentrations entering into maintenance. Further studies are needed to confirm our findings.
Background Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. Methods We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP 248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement 7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. Results A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). Conclusions NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. fig fig-type=video id=video1 orientation=portrait position="float object-id pub-id-type="doi 10.1093/ibd/izy200_video1 object-id media content-type="brightcove" orientation="portrait" position="float" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href=brightcove
Background Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD). Methods To estimate the incidence and relative risk of PD development in a cohort of adult IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis [UC]: n = 24,422; Crohn's disease [CD]: n = 11,418; IBD-unclassified [IBD-U]: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520). In a cohort design, all incident PD occurring after the index date was included from the NPR. In a case-control design, all incident PD occurring before the index date was included. The association between IBD and PD and vice versa was investigated by multivariable Cox and logistic regression. Results In IBD, there were 103 cases of incident PD, resulting in hazard ratios (HRs) for PD of 1.3 (95% confidence interval [CI], 1.0-1.7; P = 0.04) in UC, 1.1 (95% CI, 0.7-1.7) in CD, and 1.7 (95% CI, 0.8-3.0) in IBD-U. However, these effects disappeared when adjusting for number of medical visits during follow-up to minimize potential surveillance bias. In a case-control analysis, IBD patients were more likely to have prevalent PD at the time of IBD diagnosis than matched controls, with odds ratios of 1.4 (95% CI, 1.2-1.8) in all IBD patients, 1.4 (95% CI, 1.1-1.9) for UC, and 1.6 (95% CI, 1.1-2.3) for CD patients alone. Conclusions IBD is associated with an increased risk of PD, but some of this association might be explained by surveillance bias.
Background Vitamin D3 and vitamin D receptor (VDR) are involved in the pathogenesis of inflammatory bowel disease (IBD) and bacterial infection. Claudin-2 is a junction protein that mediates paracellular water transport in epithelia. Elevation of Claudin-2 is associated with active IBD. However, VDR involved in epithelial junctions under inflammation and infection remains largely unknown. We investigated the mechanisms on how VDR and Claudin-2 are related in inflamed states. Methods Using cultured VDR-/- enteroids, human intestinal epithelial cells, VDR-/- mice with Salmonella- or DSS-colitis, and human IBD samples, we investigated the mechanisms how VDR and Claudin-2 are related in inflamed states. Results After Salmonella infection had taken place, we observed significantly enhanced Claudin-2 and an increased bacterial invasion and translocation. A lack of VDR regulation led to a robust increase of Claudin-2 at the mRNA and protein levels post-infection. In DSS-treated VDR-/- mice, Claudin-2 was significantly increased. Location and quantification of Claudin-2 protein in the mouse colons treated with DSS also confirmed these results. Inflammatory cytokines were significantly higher in the serum and mRNA levels in intestine, which are known to increase Claudin-2. Furthermore, in inflamed intestine of ulcerative colitis patients, VDR expression was low and Claudin-2 was enhanced. Mechanistically, we identified the enhanced Claudin-2 promoter activity through the binding sites of NF-B and STAT in inflamed VDR-/- cells. Conclusions Our studies have identified a new role for intestinal epithelial VDR in regulating barrier functions in the context of infection and inflammation.
Background Alterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD. Methods We assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated. Results B. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-B signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model. Conclusions B. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.
Background MicroRNAs (miRNAs) are important post-translational regulators. Elevated levels of miR-206 in ulcerative colitis (UC) were associated with suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression. However, the relationship of miR-206 to histologic remission in UC patients remains unknown. This study correlates expression levels of miR-206 with histologic remission in patients treated via long-term mesalamine treatment to identify a possible mode of action for this mainstay drug for UC. Methods Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24 hours) by qRT-PCR and western blot analysis. Expression of miR-206 and pathological scores of colonoscopic biopsy specimens were studied in 10 UC patients treated with mesalamine treatment for 2 to 6 years. Results miR-206 transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine treatment in HT29 colon cells compared with untreated controls. However, the mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold, respectively, in same cells. miR-206 relative expression decreased significantly in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P = 0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies indicate a strong correlation between downregulation of miR-206 and histologic improvement (R = 0.9111). Conclusion Mesalamine treatment has an effect on epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment may confer a protective effect in inducing and maintaining histologic remission. Thus, miR-206 expression levels can be utilized as a possible biomarker for therapeutic response to mesalamine treatment.
Over the past 2 decades, advances in biologic and small molecule therapeutics have resulted in a rapid increase in our armamentarium of therapies for inflammatory bowel disease. Despite these advancements, Crohn's disease and ulcerative colitis remain chronic and progressive diseases. One of the primary reasons for persistent inflammation and bowel damage is failure of medical therapy. With growing therapeutic options, there is an increased temptation to quickly move to the next therapy and label the prior therapy as a failure; however, this can lead to inadequate optimization of medications and poor control of disease. On the other hand, failure to recognize ongoing mucosal inflammation despite optimized treatment and moving to the next agent can lead to progression of disease and long-term complications. As our options for medical therapy continue to increase, it has become more important to recognize failure of therapy in order to promptly move to the next therapeutic agent without abandoning therapies prematurely. In this review, we aim to define failure of medical therapy for inflammatory bowel disease with the goal of offering guidance on when it is appropriate to attempt optimization of current medical treatment as opposed to moving on to the next agent or treatment approach.