Moderate-severe Crohn Research Articles

Tissue markers may predict treatment response to antitumor necrosis factor-α agents in children with Crohn's disease.

Patients with moderate-severe Crohn's disease (CD) who are treated with antitumor necrosis factor alpha (TNF-α) agents may be subjected to primary nonresponse or partial response. We aimed to identify tissue markers that may predict response to these agents. Pediatric patients (6-18 years) with either ileal or ileo-colonic CD who were treated with anti-TNF-α were stratified into three different groups based on their overall response to therapy at the end of induction including clinical and laboratory parameters (group 1-full responders [FR], group 2-partial responders [PR], group 3-nonresponders [NR]). Seven tissue markers (fibronectin, interleukin [IL]-23R, IL-23, TNF-α, collagen-III, IL-13R, and hypoxia-inducible factors [HIF]-1α) were evaluated. Immunofluorescence (IF) analyses were performed on biopsies from the terminal ileum, which were retrieved up to 6 months before treatment initiation. Twenty-six CD patients (16 [61.5%] males; age 13.9 ± 2.9 years), including 8 (30.8%) with ileal disease and 18 (69.2%) with ileo-colonic disease, were enrolled. Terminal ileum biopsies from nine patients from group 1, nine from group 2, and eight from group 3 were evaluated. Three antibodies were found to be significantly different between NR and FR groups; Collagen III and fibronectin stains were significantly more prominent in NR patients, while TNF-α stain was significantly more pronounced in FR, p < 0.05 for each. PR could not have been predicted with neither of markers. Decreased tissue IF intensity of fibronectin and collagen III and increased intensity of TNF-α may predict response to anti-TNF-α treatment.

P716 Efficacy and safety of upadacitinib during induction in Crohn’s disease: Real-world experience

Abstract Background Upadacitinib is a selective JAK1 inhibitor that has recently been approved for treatment of moderate-severe Crohn’s disease, with Phase III clinical trials showing positive efficacy and safety profiles. Our aim was to evaluate the real-world experience of upadacitinib in a refractory cohort of Canadian patients with Crohn’s disease. Methods This was a two-centre retrospective study looking at 12-week induction data for patients with active Crohn’s disease from McGill University Health Centre and Hamilton Health Sciences. The primary outcome was clinical remission at 12 weeks, with secondary outcomes including clinical response, biochemical remission, and biochemical response. Clinical remission was defined as a Harvey-Bradshaw index (HBI) &amp;lt; 5. Clinical response was defined as an HBI reduction of ≥ 3. Biochemical remission was defined as a c-reactive protein (CRP) &amp;lt; 5 mg/L and/or fecal calprotectin (FCP) &amp;lt; 250 μg/g. Biochemical response was defined as a reduction of CRP or fecal calprotectin by 50% from baseline. These parameters were all evaluated at 8 and 12 weeks. Adverse events were summarized for patients who had follow up data available and included in the efficacy analysis. Results There were 28 patients who were treated in total, all of which had multiple biologic treatment failures. Baseline median age was 37, median HBI was 9, median CRP was 9.41 mg/L, and median FCP was 580 μg/g. The median disease duration was 13.5 years. Four patients discontinued upadacitinib due to no response or side effects. For all available data including patients who discontinued upadacitinib, clinical remission was achieved at 12 weeks in eight patients (8/11, 72.7%). Clinical response was achieved in eight patients (8/11, 72.7%), biochemical remission was achieved in four patients (4/11, 36.4%), and biochemical response was achieved in six patients (6/11, 54.6%). Of those that were initially on steroids (n=5), four patients (4/5, 80.0%) were able to wean off steroids and achieved a steroid-free clinical or biochemical response at 12 weeks. Of those who had previously been on off-label tofacitinib (n=5), clinical follow-up data was available for three patients at the end of the 12-week induction period. Two patients achieved clinical remission (2/3, 66.7%) and three patients had a clinical response (3/3, 100%). Among 13 patients with follow-up data, adverse events were observed in three patients (3/13, 23.1%), with two having non-serious infections (2/13, 15.4%) and one having fevers of unknown origin (1/13, 7.69%). Conclusion This real-world multicentre Canadian induction study shows favourable efficacy and tolerability of upadacitinib in refractory active Crohn’s disease.

Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia.

Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. Retrospective cohort study. Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia.

Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background and aimsThere are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. MethodsWe conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn’s disease or ulcerative colitis.ResultsWe identified six eligible Crohn’s disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn’s disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn’s disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn’s disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn’s disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.ConclusionsIndirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn’s disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-022-02347-1.

Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease.

We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after 1 year of therapy in moderate-severe Crohn's disease (CD). This was a pooled analysis of patient-level data from 299 patients with CD from 4 clinical trials. Proportions of patients treated with each biologic were compared for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). Multivariate logistic regression was used to model the relationship between biologics and 1-year outcomes and adjusted for disease duration, concomitant corticosteroid use, and prior antitumor necrosis factor failure. Compared with vedolizumab (4/56 [7.1%]), adalimumab (17/61 [27.9%], adjusted odds ratio [OR]: 5.79, 95% confidence interval [CI]: 1.77-18.95, P = 0.004) and infliximab (39/141 [27.7%], aOR: 4.59, 95% CI: 1.48-14.22, P = 0.008) had superior rates of 1-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naive patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for 1-year ileal EH. However, for large (>0.5 cm) ileal ulcers, infliximab (20/49 [40.8%]) had superior rates of no ileal ulcers compared with vedolizumab (2/23 [8.7%], aOR: 5.39, 95% CI: 1.03-28.05, P = 0.045). No other differences were observed. For colonic disease, compared with ustekinumab (9/31 [29.0%]), adalimumab (30/48 [62.5%], aOR: 3.97, 95% CI: 1.45-10.90, P = 0.007) had superior rates of 1-year EH in the colon, with similar trends observed for infliximab (55/105 [52.4%], aOR: 2.08, 95% CI: 0.82-5.27, P = 0.121). No other differences were observed. In this post hoc analysis, TNF-α antagonists were overall superior to vedolizumab and ustekinumab for achieving 1-year EH in moderate-severe CD patients.

Case Series: Re-induction of Intravenous, Weight-Based Ustekinumab Is Well Tolerated in Patients With Moderate-Severe Crohn's Disease.

Crohn's disease (CD) patients may benefit from biologic optimization. We retrospectively assessed adverse events (AEs) and clinical/endoscopic response after ustekinumab re-induction in CD patients. We identified 28 patients, all with prior biologic exposure. Eight weeks following re-induction, 10.7% reported ≥1 AE. Three serious AEs occurred in a single patient (CD flares). No infusion reactions occurred. 53.8% and 38.5% achieved clinical response and remission, respectively. 42.8% achieved both endoscopic improvement and remission. Ustekinumab re-induction was well tolerated. Clinical and endoscopic disease activity improved in some patients. Further larger studies are needed to verify these findings in a broader population.

P541 Effectiveness, safety and durability of vedolizumab in active moderate-severe Crohn’s Disease

Abstract Background Vedolizumab (VDZ) has demonstrated efficacy and safety in moderate-severe Crohn’s Disease (CD) in GEMINI registration trials. Nevertheless, the patient profile in actual clinical practice differs from that included in controlled studies so additional data are needed. The primary objective of our study was to evaluate the effectiveness, safety and durability of VDZ in active moderate-severe CD in real clinical practice. Methods Unicentric retrospective observational study. All patients treated in our center with VDZ with moderate-severe CD were included. Effectiveness was assessed 16 weeks after treatment iniciation and at the last visit with available data. Remission (RmLE) and steroid-free response (RsLE) were considered to be the achievement of a Harvey-Bradshaw index (HBI) ≤4 or a decrease of at least 3 points from the previous HBI. To evaluate the durability of VDZ, a Kaplan-Meier survival curve was performed. In addition, adverse effects attributable to VDZ during follow-up were recorded. Results We included 26 patients whose clinical-demographic features are shown in Table 1. The median follow-up of patients was 52 weeks (IQR= 24–78). At 16 weeks after initiation of VDZ treatment, RmLE and RsLE were achieved in 19.2% and 69.2% of patients respectively. At the last follow-up visit, 27% of patients achieved RmLE with 61.5% presenting RsLE (Figure 1). The probability of retention of VDZ treatment at median follow-up was 57%, not differing significantly between bionaive patients from those with previous failure to other biologic treatments (Figures 2 and 3). There were no serious adverse effects or effects that required discontinuation of VDZ. Three mild adverse effects were documented in 11.5% of patients (arthralgia, dyspnea and a mild viral infection). Conclusion In our series of patients, VDZ proved effectiveness and safety in line with that described in other real clinical practice series. The durability of VDZ at one year in this series of refractory CD was also considerable and did not vary according to previous exposure to biologic agents.

P152 Impact of disease location on burden of illness in patients with moderate-severe Crohn’s disease: A real-world survey in the United States, France, Germany, Italy, Spain, and United Kingdom (5EU)

Abstract Background Presentation and risks of progression and complications differ according to Crohn’s disease (CD) location. The objective of this study was to investigate how disease burden differs based on CD location, from physician and patient perspective. Methods Data drawn from the Adelphi Inflammatory Bowel Disease (IBD) Disease Specific Programme™, a point-in-time survey of gastroenterologists (GEs) and their IBD patients from two waves (Nov 2014-Mar 2015; Sep 2017-Jan 2018) in the United States, and 5EU. GEs completed physician-reported questionnaires for 5–10 consecutively consulting patients with CD, covering demographics, treatment, symptoms, and CD location. Same patients completed voluntary patient-reported questionnaire including outcome measures such as Short IBD Questionnaire (SIBDQ), EuroQol 5-dimension questionnaire (EQ-5D), and Work Productivity and Activity Impairment questionnaire. Comparisons were drawn between patients with CD in 3 locations: ileal only (IL), ileocolonic (IC), and colonic only (CO). Outcomes such as patient-reported level of pain, sleep disturbance, and fatigue, were compared between locations using linear regression analyses that included potential confounding variables age, gender, body mass index, comorbidities (using Charlson Comorbidity Index [CCI]) and severity at diagnosis. Least square (LS) means were generated for each location and compared using a p-value generated from Wald tests. Variables such as current treatment and symptoms, were compared using univariate tests (ANOVA, chi2 test). Base sizes varied due to the voluntary nature of patient participation. Results 686 GEs collected data on 2354 patients with moderate-severe CD, identifying patients with IL (28.3%), IC (45.7%), and CO (26.0%) location. Overall demographic characteristics were similar, mean age 39 years, proportion of male patients 51.4%, mean Body Mass Index 24.0, mean CCI 0.14. Differences were observed between the 3 groups (Table 1). Patients with ileal involvement (IL and IC) were prescribed biologics more often and had greater symptom burden than CO patients, except for rectal urgency. IL patients tended to have slightly greater burden overall in terms of symptomatology and severity. There was similarity across SIBDQ and EQ-5D scores; however, absenteeism was higher amongst IL and IC patients, compared with CO patients. Conclusion Differences were observed between IL, IC, and CO CD location groups. Despite IC patients experiencing the greatest burden overall, there were key distinctions between IL and CO patients, particularly in medication, symptoms, and work productivity impairment, suggesting that disease management with attention to CD location could lead to better patient outcomes.

S738 Re-Induction of Intravenous, Weight-Based Ustekinumab Is Well Tolerated in Patients With Moderate-Severe Crohn’s Disease

S738 Re-Induction of Intravenous, Weight-Based Ustekinumab Is Well Tolerated in Patients With Moderate-Severe Crohn’s Disease

One-year real life data of our patients with moderate-severe Crohn's disease who underwent ustekinumab therapy.

The aim of this study was to present one-year real-life data of our patients with CD who showed unresponsiveness and/or intolerance to biological agents and then received ustekinumab treatment through an early access program. The retrospective study reviewed the 52-week clinical data of 10 patients with moderate or severe CD who underwent ustekinumab therapy. The 10 patients comprised 7 (70%) men and 3 (30%) women with a mean age of 38 ± 11.3 years. Mean disease duration was 13.5 ± 8.5 years. Mean pretreatment CDAI score was 273.5 ± 92 and mean pretreatment HBI score was 11.6 ± 3.8. At the end of the 8-week intravenous induction treatment, 5 (55%) patients showed clinical remission according to the CDAI and HBI scores. Additionally, 62.5% of the patients were in clinical remission at the end of week 52 according to the CDAI and HBI scores. No drug-related side effects were observed in any patient throughout the treatment. Ustekinumab appears to be effective and safe in the treatment of moderate and severe CD, particularly in cases of unresponsiveness and intolerance to biological agents such as anti-TNF, and in the achievement of clinical remission.

Does Size Really Matter?

Ileocolonoscopy remains the mainstay of objective disease assessment in Crohn's Disease, and various validated indices are used to grade severity of the disease. The most commonly used indices are the Simple Endoscopic Score for Crohn's Disease (including the size of ulcers) and the Crohn's Disease Endoscopic Index of Severity (including the depth of ulcers). These measurements are highly subjective, especially the depth of an ulcer, and are based solely on the discretion of the endoscopist coupled with the imaging capabilities of the colonoscope and adequacy of the bowel prep. Narula et al. undertook a post hoc analysis of baseline predictors of endoscopic remission (ER) at week 26 in a subset (172 of 508) of moderate-severe Crohn's disease patients participating in the SONIC trial. The authors found no significant differences in the odds of achieving ER when comparing overall or segmental severe inflammation (high Simple Endoscopic Score for Crohn's Disease [>16 overall or >3 per segment] or Crohn's Disease Endoscopic Index of Severity [>12 overall or >3 per segment] scores) with moderate inflammation. The number of affected segments involved also did not impact the likelihood of achieving week 26 ER. The authors then found a potentially synergistic effect with large and deep ulcers in the ileum and rectum. The optimal time to assess whether ulcers ultimately heal or not is unknown, but waiting longer than 26 weeks may negate any lead time bias regarding ulcer size. Therefore, similar to many areas of life, it is likely that size ultimately does not matter, but instead location, location, and location.

The Cost-effectiveness of Biological Therapy Cycles in the Management of Crohn's Disease.

To examine the cost-effectiveness of continued treatment for patients with moderate-severe Crohn's disease in clinical remission, with a combination of anti-tumour necrosis factor alpha [anti-TNFα] [infliximab] and immunomodulator therapy compared with two different withdrawal strategies: [1] withdrawal of the anti-TNFα therapy; and [2] withdrawal of the immunomodulator therapy, respectively. A decision-tree model was constructed mimicking three treatment arms: [1] continued combination therapy with infliximab and immunomodulator; [2] withdrawal of infliximab; or [3] withdrawal of the immunomodulator. Relapses in each arm are managed with treatment intensification and re-institution of the de-escalated drug according to a prespecified algorithm. State-dependent relapse risks, remission probabilities, and quality of life weights were collected from previous published studies. Combination therapy was less costly and more efficient than the withdrawal of the immunomodulator, and more costly and more efficient than withdrawal of infliximab. Whether or not combination therapy is cost-effective, compared with the alternatives, depends primarily on current pharmaceutical prices and the willingness-to-pay per additional quality-adjusted life-year [QALY]. Combination therapy using a combination of anti-TNFα [infliximab] and an immunomodulator is cost-effective in the treatment of Crohn's disease compared with treatment cycles in which the immunomodulator is withdrawn. Combination treatment is cost-effective compared with treatment cycles in which infliximab is withdrawn, at prices of infliximab below€192/100 mg, given a willingness-to-pay threshold at€49 020 [Sweden] per additional QALY.

P703 The real-world long-term effectiveness of vedolizumab in inflammatory bowel diseases: a single-centre observational study

The effectiveness of vedolizumab (VDZ) in real-world practice is under evaluation. We aimed to report the effectiveness of VDZ on intestinal and articular symptoms after 10 and 52 weeks of treatment, and at the end of follow-up. All consecutive patients with moderate–severe Crohn’s disease (CD) or ulcerative colitis (UC) who started a treatment with VDZ from July 2016 to December 2017 were entered in a prospectively maintained database. The following clinical end-points were set at 10 and 52 weeks: steroid-free remission (Harvey–Bradshaw Index < 5 for CD and Mayo Partial Score < 2 for UC without steroids use), and response (absence of steroid-free remission, but reduction of Harvey–Bradshaw Index ≥3 for CD and Mayo Partial Score ≥2 for UC compared with baseline). Patients with steroid-free remission and response were deemed as having clinical benefit. In patients with active spondyloarthropathy (SpA) at baseline, the response on articular symptoms was defined as disappearance of objective signs of arthritis and resolution of pain. 169 patients (112 with CD and 57 with UC) were included. At Week 10, a steroid-free remission was achieved in 44 out of 169 patients (26.0%), and a response in 35 (20.7% - overall clinical benefit: 46.7%), while at 52 weeks a steroid-free remission was achieved in 30 out of 128 patients (23.4%), and a response in 18 (14.1% - overall clinical benefit: 37.5%). The median follow-up was 47.0 weeks (148.39 person-years), and the failure-free survival was 60.4% at 1 year. Semi-parametric Cox model showed that patients with CD had a higher risk of treatment failure compared with patients with UC (HR 2.06, 95% CI: 1.05–4.05, p = 0.036). After 10 weeks, a response on articular symptoms was reported in 12 out of 39 patients (30.8%) with active SpA at baseline, and in 12 out of 16 patients (75.0%) at Week 52. At Week 10, the only factor that was marginally associated with the articular response was the clinical benefit on intestinal symptoms (OR 5.07, 95% CI: 0.97–31.70, p = 0.055), while the coexistence of axial and peripheral SpA was associated with a reduced response rate compared with peripheral manifestations only (OR 0.13, % CI: 0.02–0.64, p = 0.021). Overall, 67 adverse events were reported (incidence rate: 45.2 per 100 person-years). Twenty (11.8% of patients) adverse events leading to treatment discontinuation were reported: 11 arthritic flares, 5 subjective perceptions of intolerance, 2 infusion reactions, one pneumonia, and one prostate cancer. In this large cohort, VDZ provided good effectiveness on intestinal symptoms, particularly in patients with UC. A subset of patients reported improvement also on articular symptoms, especially in cases of peripheral SpA.

Cost-Effectiveness Comparison of Ustekinumab, Infliximab, or Adalimumab for the Treatment of Moderate-Severe Crohn's Disease in Biologic-Naïve Patients.

Ustekinumab was recently approved by the United States U.S. Food and Drug Administration for the treatment of Crohn's disease. In this analysis, we aimed to compare the cost-effectiveness of ustekinumab, infliximab, or adalimumab for the treatment of moderate-severe Crohn's disease in patients who failed conventional therapy (i.e., corticosteroids and immunomodulators) but were naïve to tumor necrosis factor antagonists (i.e., biologic drugs). Cost-effectiveness analysis using a hybrid model structure (decision tree and Markov model). A decision tree simulated biologic induction, and a Markov model simulated biologic and conventional therapy maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a limited U.S. societal perspective in the base case; results from a payer perspective are also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained from the literature. To measure relative treatment value (i.e., order of treatment cost-effectiveness), net monetary benefits were reported for a $150,000 willingness-to-pay threshold per quality-adjusted life-year in the base case. Infliximab dominated both adalimumab and ustekinumab, with a net monetary benefit (NMB) of $9943 and $29,798, respectively, in the base case. Adalimumab dominated ustekinumab, with an NMB of $19,855. All biologics yielded similar quality-adjusted life-years (~3.5), whereas costs varied substantially ($50,510, $54,985, and $72,921 for infliximab, adalimumab, and ustekinumab, respectively). The payer perspective, alternate time horizons, and scenario analyses consistently showed infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirmed the robustness of these results with respect to all parameters. Although biosimilars were not explicitly modeled as comparators, one-way sensitivity analysis showed that drug acquisition costs could alter relative treatment value but would have to be varied by at least 50%. For moderate-severe Crohn's disease, infliximab yields significantly more NMBs compared with both adalimumab and ustekinumab. Additional clinical (e.g., empiric dosing, biologic cycling) and quality-of-life (e.g., lost productivity, disutility of home injections) research is needed to allow for model frameworks and parameters that more accurately reflect the nuances of Crohn's disease treatment.

Epidemiological features and disease-related concerns of a large cohort of Italian patients with active Crohn’s disease

Background-AimsThe SOLE study was conducted on a large cohort of Italian patients with moderate-severe Crohn’s disease (CD) to assess epidemiological and disease characteristics and their correlation with disease-related worries, treatment satisfaction and adherence, workability. MethodsThe following tools were used over 12 months to assess:•disease-related worries: Rating Form of Inflammatory Bowel Disease Patient Concerns,•impact on workability: Work Productivity and Activity Impairment-CD,•satisfaction: Treatment Satisfaction Questionnaire for Medication,•adherence: Medication Adherence Rating Scale.Results were correlated with demographic and clinical variables with linear regression models. Results552 patients with active CD (51% men) were recruited. Higher worries were having an ostomy bag and undergoing surgery. Variables associated with a higher RFIPC score included female sex, higher disease activity, lower treatment adherence (p < 0.001), previous surgical treatments (p = 0.003). 60% of patients claimed difficulties with activities of daily living. Lower VAS scores were reported by patients with disease duration >6years; treatment satisfaction/adherence was higher with anti-TNF-α treatment. Decreased hospitalizations during follow-up and improved workability/daily activities occurred with adalimumab, infliximab, azathioprine (p < 0.001). ConclusionWorries included having an ostomy bag, undergoing surgery, developing cancer: conditions significantly associated with worsened disease activity and low treatment adherence. Higher treatment adherence scores/greater workability improvements were observed in patients treated with anti-TNF-α agents.

Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn's disease.

There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We identified randomised controlled trials (RCTs) in adults with moderate-severe CD treated with approved anti-TNF agents, anti-integrin agents and anti-IL12/23 agents, first-line or second-line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. No head-to-head trials were identified. In biologic-naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti-TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti-TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials. Indirect comparisons suggest that infliximab or adalimumab may be preferred first-line agents, and ustekinumab a preferred second-line agent, for induction of remission in patients with moderate-severe CD. Head-to-head trials are warranted.

Sa1771 - Double-Blind, Randomized, Placebo-Controlled, Crossover Trial to Evaluate Induction of Clinical Response in Patients with Moderate-Severe Crohn's Disease Treated with Rifaximin

Sa1771 - Double-Blind, Randomized, Placebo-Controlled, Crossover Trial to Evaluate Induction of Clinical Response in Patients with Moderate-Severe Crohn's Disease Treated with Rifaximin

PGI17 - The Cost-Effectiveness of Ustekinumab Compared to Infliximab And Adalimumab in Adult Patients with Moderate-Severe Crohn's Disease (Tnf Naïve Population)

Ustekinumab was recently approved by the FDA for the treatment of Crohn’s disease (CD). This model evaluates the cost-effectiveness of ustekinumab compared with infliximab and adalimumab for the treatment of moderate-severe CD in patients that have failed conventional therapy but are naïve to tumor necrosis factor antagonists. A decision tree simulated biologic induction and a Markov model simulated biologic and conventional therapy (CT) maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a US societal perspective in the base case; the payer perspective is also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained or derived from literature. Incremental net monetary benefits (NMBs) are reported for a $150,000 willingness to pay (WTP) threshold per quality-adjusted life-year (QALY) in the base case. Infliximab dominates both adalimumab and ustekinumab with incremental NMBs of $9,943 and $29,798 respectively in the base case. All biologics yield similar QALYs while costs vary significantly. The payer perspective, alternate time horizons, and scenario analyses consistently show infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirm the robustness of results with respect to all parameters. Threshold sensitivity analysis indicates that lower biologic induction efficacy yields higher treatment value. This result is explained by CT maintenance treatment value: patients who fail to respond during biologic induction avoid high biologic maintenance costs and still experience significant QALY gains from CT maintenance. Threshold sensitivity analysis also indicates that adalimumab has highest relative treatment value when average hourly compensation is more than $621 per hour. For moderate-severe CD, infliximab yields slightly more QALYs at a significantly lower cost compared to both adalimumab and ustekinumab. Drug acquisition costs are the only parameters that could alter relative treatment value but would have to be varied by at least 50% to do so.

Sa1772 - Sustained Clinical Remission with Vedolizumab in Moderateto-Severe Crohn's Disease: A Gemini 2 Post HOC Analysis of Week 14 Remitters

Sa1772 - Sustained Clinical Remission with Vedolizumab in Moderateto-Severe Crohn's Disease: A Gemini 2 Post HOC Analysis of Week 14 Remitters

P142 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, CROSSOVER TRIAL TO EVALUATE INDUCTION OF CLINICAL RESPONSE IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE TREATED WITH RIFAXIMIN

Antibiotics have been used to treat luminal Crohn’s disease (CD) with variable success. Rifaximin has a favorable safety profile given its limited systemic absorption. Studies suggest clinical improvement in patients with mild-moderate CD treated with rifaximin. Studies evaluating response to rifaximin in moderate-severe luminal CD are limited. We randomized 24 subjects eligible per protocol with moderate-severe CD (Crohn’s disease activity index (CDAI) 250–450) 1:1 to receive blinded rifaximin 550 mg PO BID or placebo for 8 weeks. Non-responders to placebo then received open label (OL) rifaximin 550 mg PO BID for 8 weeks. Assessments include disease activity by CDAI, quality of life by Inflammatory Bowel Disease Questionnaire (IBDQ), and biochemical assessments including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Adverse events were documented throughout the study and 8 weeks after the last dose. Key characteristics of 24 subjects eligible per protocol are described in Table 1. After 8 weeks of blinded treatment, 38.5% of subjects reported clinical response by CDAI in the treatment arm, compared to 9.1% in the control population (P = 0.055 by non-parametric permutation test). Ten subjects with nonresponse to placebo received OL rifaximin. Five subjects completed the OL study. 1 subject withdrew consent and 4 discontinued early due to lack of efficacy. At week 8, 1 subject had clinical response and no subjects were in remission by CDAI. Adverse events were similar between groups. Rifaximin has a moderate impact on clinical disease activity in moderate-severe Crohn’s disease, even in patients with a significant disease burden and prior exposure to one or more biologic therapies. Quality of life and biochemical assessments were numerically improved. No new safety concerns were identified.