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Background: The understanding the Impact of ulcerative COlitis aNd Its assoCiated disease burden on patients study [ICONIC] was a 2-year, global, prospective, observational study evaluating the cumulative burden of ulcerative colitis [UC] using the Pictorial Representation of Illness and Self-Measure [PRISM] tool that is validated to measure suffering, but not previously used in UC., Methods: ICONIC enrolled unselected outpatient clinic attenders with recent-onset UC. Patient- and physician-reported outcomes including PRISM, the Short Inflammatory Bowel Disease Questionnaire [SIBDQ], the Patient Health Questionnaire [PHQ-9], and the Simple Clinical Colitis Activity Indexes [patient: P-SCCAI; physician: SCCAI] were collected at baseline and follow-up visits every 6 months. Correlations between these measures were assessed using Spearman's rank correlation coefficient., Results: Overall, 1804 evaluable patients had ≥1 follow-up visit. Over 24 months, mean [SD] disease severity measured by P-SCCAI/SCCAI reduced significantly from 4.2 [3.6]/3.0 [3.0] to 2.4 [2.7]/1.3 [2.1] [p<0.0001]. Patient-/physician-assessed suffering, quantified by PRISM, reduced significantly over 24 months [p<0.0001]. SCCAI/P-SCCAI, and patient-/physician-assessed PRISM, showed strong pairwise correlations [rho ≥0.60, p<0.0001], although physicians consistently underestimated these disease severity and suffering measures compared with patients. Patient-assessed PRISM moderately correlated with other outcome measures, including SIBDQ, PHQ-9, P-SCCAI, and SCCAI (rho = ≤-0.38 [negative correlations] or ≥0.50 [positive correlations], p<0.0001)., Conclusion: Over 2 years, disease burden and suffering, quantified by PRISM, improved in patients with relatively early UC. Physicians underestimated burden and suffering compared with patients. PRISM correlated with other measures of illness perception in patients with UC, supporting its use as an endpoint reflecting patient suffering., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Management of Crohn's disease and ulcerative colitis has typically relied upon treatment intensification driven by symptoms alone. However, a 'treat-to-target' management approach may help to address underlying inflammation, minimise disease activity at early stages of inflammatory bowel disease, limit progression, and improve long-term outcomes., Methods: A systematic literature review was conducted to identify data relevant to a treat-to-target approach in inflammatory bowel disease, published between January 1, 2007 and May 15, 2017., Results: Consistent with recommendations of the Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE] working group, studies have investigated factors influencing the achievement of both endoscopic and histological mucosal healing and patient-level outcomes in inflammatory bowel disease [IBD]. Histological healing and biomarker levels have also been shown to be modifiable outcomes. Although there is a lack of prospectively derived evidence validating mucosal healing as a treatment target, data are emerging to suggest that targeting mucosal healing or inflammation rather than symptoms may be cost-effective in some settings. The review highlighted several strategies that may support the implementation of a treat-to-target approach in IBD. The prospective randomised CALM study demonstrated how tight control [whereby treatment decisions are based on close monitoring of inflammatory biomarkers] leads to improvements in endoscopic and clinical outcomes. The review also considered the influence of coordinated care from a multidisciplinary team and patient engagement with improved adherence, as well as the role of therapeutic drug monitoring in inflammatory bowel disease management., Conclusions: A treat-to-target strategy may impact on disease progression and improve outcomes in inflammatory bowel disease. Prospective studies including long-term data are required to ensure that the most appropriate targets and strategies are identified., (© The Author(s) 2019. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: The efficacy and safety of adalimumab for induction and maintenance of clinical remission in patients with moderately to severely active ulcerative colitis were demonstrated in the ULTRA 1 and 2 clinical trials. This post-hoc, pooled analysis evaluated early changes in laboratory parameters, Mayo subscores, mucosal healing, and health-related quality of life., Methods: Mean changes in laboratory parameters including albumin, high-sensitivity C-reactive protein, total protein, haematocrit, haemoglobin, red blood cell and platelet counts, Inflammatory Bowel Disease Questionnaire, and Short Form 36 Health Survey were evaluated from baseline to Weeks 4 and 8. Mean changes in Mayo subscores of rectal bleeding and stool frequency were evaluated from baseline to Weeks 2, 4, 6, and 8. Mucosal healing was assessed with endoscopy at baseline and Week 8. Categorical variables were evaluated with the Cochran-Mantel-Haenszel test; continuous variables were evaluated with analysis of covariance and considered significant if p <0.05., Results: Treatment with adalimumab significantly improved laboratory and quality-of-life measures at Weeks 4 and 8 compared with placebo [p <0.05 and p <0.001]. Mean reductions from baseline in rectal bleeding and stool frequency were significantly larger in patients receiving adalimumab compared with placebo at Week 2 and sustained through Week 8 [p <0.01]. Normal mucosa at Week 8 was achieved by 13% of patients receiving adalimumab compared with 6% of those receiving placebo [p <0.001]., Conclusions: Adalimumab resulted in rapid improvements in laboratory markers and early reductions in rectal bleeding and stool frequency. Early improvement in quality-of-life scores correlated with the clinical and laboratory findings., (© European Crohn’s and Colitis Organisation (ECCO) 2019.)

Background: PYRAMID was an international multicenter, noninterventional, postmarketing registry assessing long-term safety and effectiveness of adalimumab (Humira), as used in routine clinical practice., Methods: Adult patients with moderately to severely active Crohn's disease with or without prior adalimumab experience were enrolled in the registry and followed for up to 6 years. Effectiveness measurements included the Physician's Global Assessment (PGA, a composite of Harvey Bradshaw Index [HBI] and rectal bleeding score), clinical remission (HBI < 5), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Work Productivity and Activity Impairment (WPAI) questionnaire. Data were reported for adalimumab-naïve patients and analyzed by baseline immunomodulator use and disease duration., Results: This study evaluated 2057 adalimumab-naïve patients. Mean PGA improved from 7.5 (baseline) to 3.9 (year 1) and 3.3 (year 6). The proportion of patients in HBI remission increased from 29% (573 of 1969; baseline) to 68% (900 of 1331; year 1) and 75% (625 of 831; year 6). Patients stratified by baseline immunomodulator use had similar HBI remission rates; patients with disease duration <2 years achieved numerically higher HBI remission rates than patients with longer disease duration. Patient-reported SIBDQ and WPAI scores improved at year 1; all WPAI subscore improvements were clinically meaningful (≥7% point change) at year 1 and maintained through year 6. Serious infections were reported in 11.1% of patients; incidence rates of malignancies, lymphoma, and demyelinating disorders were low., Conclusion: Adalimumab therapy, as used in routine clinical practice, improved physician-reported and patient-reported disease outcomes and remission rates for up to 6 years. No new safety signals were observed., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background and Aims: Analyses of Crohn's Disease [CD] studies of anti-TNF agents, including adalimumab, have reported higher remission rates among patients with shorter disease duration. To further explore the relationship between disease duration and clinical efficacy, we analysed a larger patient cohort., Methods: Data were pooled from 10 clinical trials in patients with moderately to severely active CD who received treatment with either adalimumab or placebo. Analyses of efficacy using Crohn's Disease Activity Index [CDAI] endpoints [remission, clinical response [CR]-70, CR-100, patient-reported outcome [PRO] remission] or Harvey-Bradshaw Index [HBI] endpoints [remission/response] were conducted for induction and maintenance treatment periods. Logistic regression was used for comparisons between adalimumab and placebo treatment. Cochran-Armitage trend tests were used for comparisons between disease-duration subgroups [<1 year, ≥1-<2 years, 2-≤5 years, and >5 years]., Results: During induction, the proportion of patients achieving CDAI remission was higher in adalimumab- versus placebo-treated patients [p <0.001] and was highest [adalimumab: 45.8%] in the <1 year subgroup compared with longer disease-duration subgroups [≥1-<2 years: 31.0%; 2-≤5 years: 23.1%; >5 years: 23.6%, Cochran-Armitage p = 0.026]. In the majority of maintenance treatment analyses, patients with <1 year disease duration had the highest efficacy responses, with statistically significant differences in remission rates across disease-duration subgroups., Conclusions: This analysis demonstrates that earlier initiation of adalimumab treatment shortly after diagnosis in patients with moderately to severely active CD leads to improved long-term clinical outcomes., (© European Crohn’s and Colitis Organisation (ECCO) 2019.)

Background and Aims: In the 4-week GAIN clinical trial, adalimumab was efficacious in inducing remission in patients with moderate-to-severe Crohn's disease [CD] who had prior loss of response/intolerance to infliximab. The efficacy and safety of adalimumab in these patients are reported here for up to 96 weeks or for 3 years, respectively, in the ADHERE open-label extension study., Methods: Patients who completed GAIN could enrol in ADHERE and receive open-label adalimumab 40 mg every other week. Efficacy variables included clinical response (Crohn's Disease Activity Index [CDAI] decrease from baseline ≥70/≥100 points [CR-70/CR-100]) and remission [CDAI<150], steroid discontinuation and fistula remission [absence of drainage]. Data were reported using hybrid non-responder imputation [hNRI], last observation carried forward and as-observed analysis. Subgroup analyses were performed by randomized group in GAIN and by Week 4 efficacy in GAIN. Safety was also assessed., Results: A total of 310 patients from GAIN enrolled in ADHERE. CR-70, CR-100 and remission rates at Week 96 were 39.0%, 35.5%, and 26.5% [hNRI], respectively. Of the patients with CR-70 response or remission at Week 4 of GAIN, 45.5% and 44.4% [hNRI], respectively, maintained the effect at Week 96. Steroid discontinuation and steroid-free remission rates increased from Week 12 to 96 in patients using corticosteroids at GAIN baseline., Conclusions: Long-term adalimumab maintenance therapy led to sustained clinical remission and response, and steroid discontinuation in a considerable proportion of patients with CD previously treated with infliximab. No new safety signals were observed in this patient population.

Background and Aims: Randomised trials have described the benefits of adalimumab [ADA] for ulcerative colitis [UC]; however, few data are available on health-related quality of life [HRQL] and health care costs in clinical practice., Methods: InspirADA, a multicentre, prospective study, evaluated the effect of ADA in patients with moderate to severe UC treated according to usual clinical practice. Outcomes assessed were: Simple Clinical Colitis Activity Index [SCCAI] response/remission rates; changes in HRQL; all-cause direct costs; and UC-related direct and indirect costs from baseline to Week 26., Results: Data from 463 patients were analysed. At Week 26, 67% (95% confidence interval [CI]: 62%, 71%) of patients achieved response; 48% [95% CI: 44%, 53%] were in remission. For the overall population, significant [all p < 0.001] improvements from baseline to Week 26 were observed for the Short Inflammatory Bowel Disease Questionnaire [SIBDQ] (mean change ± standard deviation [SD]: 17.4 ± 14.5) and the European Quality of Life-5 Dimensions-5 Level [EQ-5D-5L] (index: 0.1 ± 0.2; visual analogue scale [VAS]: 19.5 ± 25.8). Parallel improvements were seen in work productivity [11% absolute decrease in absenteeism; 25% absolute decrease in impairment while working; and 27% absolute decrease in impairment of ability to perform daily activities, all p < 0.001]. Among study completers, cumulative all-cause medical costs and UC-related medical costs were significantly [both p < 0.001] reduced by 59% and 77%, respectively, 6 months after initiation of therapy compared with the preceding 6 months. The safety profile of ADA was consistent with that observed in previous clinical trials., Conclusions: ADA therapy in usual clinical practice is effective at improving and maintaining symptomatic control, improving HRQL, and decreasing costs of medical care among patients with UC., (© European Crohn’s and Colitis Organistion (ECCO) 2017.)

Background and Aims: Mucosal healing [MH] is an important goal for patients with Crohn's disease [CD], yet is incompletely characterised. We investigated whether MH differed by segments across the colon and ileum in patients who received adalimumab maintenance treatment in the EXTEND study., Methods: In this double-blind study in adults with moderate to severe ileocolonic CD and mucosal ulceration, all patients received adalimumab induction [Week 0, 160 mg; Week 2, 80 mg]. At Week 4, patients were randomised to 40 mg adalimumab or placebo every other week until Week 52. In this post-hoc analysis, MH was assessed by CD Endoscopic Index of Severity [CDEIS], Simple Endoscopic Score for CD [SES-CD], and Colonic and Ileal Global Histologic Disease Activity Scores [CGHAS/IGHAS]., Results: Baseline endoscopic severity was similar across segments. At Week 52, mean changes in CDEIS surface involved and ulcerated surface were -68.5% to -90.6% in the rectum, sigmoid/left colon, and transverse colon compared with -22.3% to -50.0% in the right colon and ileum. Favourable shifts by Week 52 in ulcer size and ulcerated surfaces per SES-CD were more pronounced in the rectum, sigmoid/left colon, and transverse colon vs the right colon and ileum. At Week 52, CGHAS and IGHAS healing was more common in the colon [28.3%] vs the ileum [21.2%]., Conclusions: This analysis suggests differing propensities of the ileocolonic segments to heal endoscopically during adalimumab treatment. In the sigmoid/left and transverse colon, higher MH rates may be achieved, compared with the ileum, in patients with moderate to severe CD., (© European Crohn’s and Colitis Organistion (ECCO) 2016.)

Background and Aims: Adalimumab has been shown to be effective and well tolerated in patients with Crohn's disease. This analysis reports the results of a cohort of Japanese patients with moderate to severe Crohn's disease who were evaluated for up to 3years to assess the long-term use of adalimumab., Methods: The study consisted of a double-blind part and an open-label part. Patients were included either in the 52-week double-blind, placebo-controlled part of the study followed by a 96-week open-label extension or in the open-label part from the beginning or in the event of a flare. Patients were treated with adalimumab and evaluated for up to 148weeks as 3 data cohorts: the all-adalimumab cohort (patients receiving ≥1 injection of adalimumab), the 148-week follow-up subcohort (patients who completed 148weeks of follow-up after the first adalimumab dose), and the dose-escalation subcohort (patients receiving adalimumab doses that increased to 80mg every other week)., Results: In the all-adalimumab cohort (n=79), clinical remission rates were approximately 30% after 36weeks of exposure to adalimumab and for the remainder of the study (35%, 33%, and 28% for weeks 48, 108, and 144, respectively). An improvement in quality of life was also maintained over the same period. In the dose-escalation subcohort (n=40), the clinical remission rate was 75% (6/8) 48weeks after dose escalation. Adalimumab was tolerated, and no deaths were reported., Conclusions: Adalimumab is effective for maintaining long-term clinical remission in Japanese patients with moderate to severe Crohn's disease (NCT00445432)., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Inflammatory bowel diseases are part of a wider conglomeration of immune-mediated inflammatory diseases. New management approaches need to be developed as we understand more of the epidemiology and aetiology of inflammatory bowel diseases and medical care becomes more complex., Methods: Selected new tools and approaches for improved management of inflammatory bowel diseases are presented, based on published evidence and clinical experience., Results: Setting quality of care standards that are consistent across different inflammatory bowel disease care settings will be paramount and require collaboration between specialist and non-specialist centres. Alongside this, the value of care will need to be evaluated in terms of maximising outcomes over the entire care cycle for a patient. In moving towards a value-based approach to management, it is important to determine the progression rate of the disease by measuring cumulative bowel damage. As well as understanding the course of disease in individual patients, it is also becoming more feasible to individualise therapy and exploit drug pharmacology to achieve better and more long-term responses. Finally, it is timely to consider formal collaborations between specialists in immune-mediated inflammatory diseases to ensure more cohesive patient care., Conclusions: The potential for improved management of patients with inflammatory bowel diseases continues to increase as we look to understand when and how to intervene in the disease process and how to adopt a collaborative management approach that promotes networking and reduces heterogeneity of care across different care settings., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Treatment goals in inflammatory bowel diseases are evolving beyond the control of symptoms towards the tight control of objectively-measured gastrointestinal inflammation. This review discusses the progress and challenges in adopting a treat-to-target approach in inflammatory bowel diseases., Methods: Evidence from the literature that highlights current thinking in terms of treating-to-target in patients with inflammatory bowel diseases is discussed., Results: Monitoring for objective evidence of inflammation using endoscopy, cross-sectional imaging or laboratory biomarkers may be a useful approach in inflammatory bowel diseases; however, setting the appropriate treatment goal remains a challenge. Deep remission (a composite of symptom control and mucosal healing) may now be a realistic target in Crohn's disease; however, it remains to be proven that achieving deep remission will modify the long-term disease course. Assessing prognosis at an early stage of the disease course is essential for the development of an appropriate management plan, with the rationale of adapting treatment to disease severity. An algorithm has been proposed for the treatment of early Crohn's disease that involves early treatment with immunosuppressants and tumour necrosis factor antagonists, in the hope of preventing structural bowel damage., Conclusions: Treating beyond symptoms will require a clear management plan influenced by disease severity at presentation, clinical and biological prognostic factors, achievement and maintenance of clinical and biological remission and pharmacoeconomics., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: There are a number of gaps in our current quality of care for patients with inflammatory bowel diseases. This review proposes changes that could be made now to improve inflammatory bowel disease care., Methods: Evidence from the literature and clinical experience are presented that illustrate best practice for improving current quality of care of patients with inflammatory bowel diseases., Results: Best care for inflammatory bowel disease patients will involve services provided by a multidisciplinary team, ideally delivered at a centre of excellence and founded on current guidelines. Dedicated telephone support lines, virtual clinics and networking may also provide models through which to deliver high-quality, expert integrated patient care. Improved physician-patient collaboration may improve treatment adherence, producing tangible improvements in disease outcomes, and may also allow patients to better understand the benefits and risks of a disease management plan. Coaching programmes and tools that improve patient self-management and empowerment are likely to be supported by payers if these can be shown to reduce long-term disability., Conclusions: Halting disease progression before there is widespread bowel damage and disability are ideal goals of inflammatory bowel disease management. Improving patient-physician communication and supporting patients in their understanding of the evidence base are vital for ensuring patient commitment and involvement in the long-term management of their condition. Furthermore, there is a need to create more centres of excellence and to develop inflammatory bowel disease networks to ensure a consistent level of care across different settings., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Clinical management of inflammatory bowel diseases (IBD), new treatment modalities and the potential impact of personalised medicine remain topics of intense interest as our understanding of the pathophysiology of IBD expands., Methods: Potential future strategies for IBD management are discussed, based on recent preclinical and clinical research., Results: A top-down approach to medical therapy is increasingly being adopted for patients with risk factors for severe inflammation or an unfavourable disease course in an attempt to halt the inflammatory process as early as possible, prevent complications and induce mucosal healing. In the future, biological therapies for IBD are likely to be used more selectively based on personalised benefit/risk assessment, determined through reliable biomarkers and tissue signatures, and will probably be optimised throughout the course of treatment. Biologics with different mechanisms of action will be available; when one drug fails, patients will be able to switch to another and even combination biologics may become a reality. The role of biotherapeutic products that are similar to currently licensed biologics in terms of quality, safety and efficacy - i.e. biosimilars - is at an early stage and requires further experience. Other therapeutic strategies may involve manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet and combinations of all these approaches. Faecal microbiota transplantation is also a potential option in IBD although controlled data are lacking., Conclusions: The future of classifying, prognosticating and managing IBD involves an outcomes-based approach to identify biomarkers reflecting various biological processes that can be matched with clinically important endpoints., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)