Karen Kemp

ECCO Position Statement on the Use of Biosimilars for Inflammatory Bowel Disease—An Update

Biosimilars of infliximab were first approved by the European Medicine Agency in 2013,1 , 2 based on pre-clinical studies on biosimilarity and on clinical data coming from two randomised controlled trials conducted in rheumatoid arthritis [RA] and ankylosing spondylitis [AS].3 , 4 Initially the European Crohn’s Colitis Organisation [ECCO] raised some caution on the use of biosimilars.5 This cautious approach was also supported by several national inflammatory bowel disease [IBD] societies5–12 [Table 1]. An insufficient understanding of the characteristics and use of biosimilars became evident in a web survey among ECCO members in the same period.13 View this table: Table 1. Available society guidelines. Since biosimilars were introduced in the EU market in early 2015, more data from IBD patients14–19 have supported the biosimilarity of biosimilar infliximab CT-P13 and the reference product, with no significant differences in terms of efficacy or safety, in either naive or switched patients in cohort studies. Importantly, a study showed clear cross-reactivity between the infliximab originator and CT-P13.20 Recently, a large nationwide Norwegian randomised controlled trial [NOR-SWITCH] on patients with immune-mediated diseases [Crohn’s disease; ulcerative colitis; psoriasis; psoriatic arthritis; RA and AS] found no differences in terms of clinical response, maintenance of remission, or adverse events in patients receiving CT-P13 compared with those receiving originator infliximab.21 Consideration of these findings22 together with a better understanding of the process of biosimilar development and regulatory approval, have contributed to a change in the perception of IBD experts, who now prescribe biosimilars with significantly more confidence.23 A task-force including Governing Board representatives and one representative from pertinent ECCO Committees performed a literature search and made relevant statements to summarise their shared position. The proposed statements were then discussed, agreed and approved in a Consensus meeting. The licensing of any biosimilar medication …

What are the top 10 research questions in the treatment of inflammatory bowel disease? A Priority Setting Partnership with the James Lind Alliance

Background and Aims: Many uncertainties remain regarding optimal therapies and strategies for the treatment of inflammatory bowel disease. Setting research priorities addressing therapies requires a partnership between health care professionals, patients and organisations supporting patients. We aimed to use the structure of the James Lind Alliance Priority Setting Partnership, which has been used in other disease areas, to identify and prioritise unanswered questions about treatments for inflammatory bowel disease. Methods: The James Lind Priority Setting Partnership uses methods agreed and adopted in other disease areas to work with patients and clinicians: to identify uncertainties about treatments; to agree by consensus a prioritised list of uncertainties for research; then to translate these uncertainties into research questions which are amenable to hypothesis testing; and finally to take results to research commissioning bodies to be considered for funding. Results: A total of 1636 uncertainties were collected in the initial survey from 531 respondents, which included 22% health care professionals and 78% patients and carers. Using the rigorously applied processes of the priority setting partnership, this list was distilled down to the top 10 research priorities for inflammatory bowel disease. The top priorities were: identifying treatment strategies to optimise efficacy, safety and cost-effectiveness; and stratifying patients with regard to their disease course and treatment response. Diet and symptom control [pain, incontinence and fatigue] were also topics which were prioritised. Conclusions: A partnership involving multidisciplinary clinicians, patients and organisations supporting patients has identified the top 10 research priorities in the treatment of patients with inflammatory bowel disease.

Identification of Research Priorities for Inflammatory Bowel Disease Nursing in Europe: a Nurses-European Crohn’s and Colitis Organisation Delphi Survey

Background Robust research evidence should inform clinical practice of inflammatory bowel disease [IBD] specialist nurses, but such research is currently very limited. With no current agreement on research priorities for IBD nursing, this survey aimed to establish topics to guide future IBD nursing research across Europe. Methods An online modified Delphi survey with nurse and allied health professional members of the Nurses European Crohns and Colitis Organisation [n = 303] was conducted. In Round One, participants proposed topics for research. In Round Two, research topics were rated on a 1-9 scale and subsequently synthesised to create composite research questions. In Round Three, participants selected their top five research questions, rating these on a 1-5 scale. Results Representing 13 European countries, 88, 90 and 58 non-medical professionals, predominantly nurses, responded to Rounds One, Two and Three, respectively. In Round One, 173 potential research topics were suggested. In Rounds Two And Three, responders voted for and prioritised 125 and 44 questions, respectively. Round Three votes were weighted [rank of 1 = score of 5], reflecting rank order. The top five research priorities were: interventions to improve self-management of IBD; interventions for symptoms of frequency, urgency and incontinence; the role of the IBD nurse in improving patient outcomes and quality of life; interventions to improve IBD fatigue; and care pathways to optimise clinical outcomes and patient satisfaction. Conclusions The prioritised list of topics gives clear direction for future IBD nursing research. Conducting this research has potential to improve clinical practice and patient-reported outcomes.

A qualitative study of the impact of Crohn's disease from a patient's perspective

Objective To understand how the lives of people with Crohns disease (CD) are affected. Most research in CD has focused on symptoms and functioning rather than on how these outcomes influence quality of life (QoL). Design As part of a study to develop a CD-specific patient-reported outcome measure, qualitative interviews were conducted with patients from Manchester Royal Infirmary to determine how CD affects QoL. The needs-based model was adopted for the study. The interviews, which took the form of focused conversations covering all aspects of the impact of CD and its treatment, were audio-recorded. Theoretical thematic analysis of the transcripts identified needs affected by CD. Results Thirty patients (60% female) aged 25–68 years were interviewed. Participants had experienced CD for between 2 and 40 years. Nearly 1300 statements relating to the impact of CD were identified. Thirteen main need themes were identified: nutrition, hygiene, continence, freedom from infection, security, self-esteem, role, attractiveness, relationships, intimacy, clear-mindedness, pleasure and autonomy. Conclusions The findings from the interviews indicate that CD has a major impact on need-fulfilment. Such issues should be addressed in CD audit, clinical trials and when evaluating clinical practice.

An evaluation study of a pilot group education programme for inflammatory bowel disease

Background and aims The emphasis for healthcare clinicians to provide adequate disease-related education is increasing. Yet little is known about the effect of providing disease-related education within inflammatory bowel disease (IBD). Previous studies have demonstrated increased levels of knowledge and satisfaction, but failed to capture any positive effects on the psychosocial elements of living with IBD. The aim of this qualitative study was to evaluate the impact of providing a group patient education programme on the psychosocial elements of living with IBD. Methods The data were obtained through eight semistructured qualitative interviews. Participants were recruited at the education programme using purposive sampling. All the interviews were digital recorded and transcribed. Thematic analysis was used by two independent researchers to analyse the transcripts and agreed emerging themes. Results A global theme of ‘mastery’ was evident within the transcripts. This was underpinned with two core themes of enablement and cooperative learning. The education programme ‘enabled’ the participants in a variety of ways: increased confidence, control, courage and power over their disease. An unexpected core theme of cooperative learning was also identified, with participants describing the overwhelming benefit of interaction with other people who also had IBD. Conclusions This is the first qualitative study to report on the effects of providing a group patient education within IBD. The results identify new and interesting psychosocial elements that existing quantitative studies have failed to identify.

PTU-080 Development and Validation of the Crohn’S Life Impact Questionnaire (Cliq)

Introduction Crohn’s Disease (CD) is a chronic, inflammatory, autoimmune disorder that substantially impairs patients’ physical and emotional well-being. Despite this there is no CD-specific patient-reported outcome measure (PROM) available for determining the efficacy of alternative interventions for the condition. The objective of the study is to develop and validate the first such patient-reported outcome measure. Questionnaire content was derived from 30 qualitative interviews conducted with UK CD patients. Cognitive debriefing interviews conducted with a new sample of 15 CD patients indicated that the draught scales were relevant, clear and easy to use. Methods A test-retest postal survey was conducted to; identify the final scales, confirm their unidimensionality (by means of Rasch analysis) and to determine reproducibility and construct validity. A subset of the respondents was sent a second questionnaire package 2 weeks after completing the first. The package included the CLIQ, the Nottingham Health Profile (NHP), the Unidimensional Fatigue Impact Scale (U-FIS) and a demographic questionnaire. Results The questionnaire package was completed by 273 CD patients (34.4% male; aged 16–79 (mean: 43.9; SD 15.1) years). Of these, 107 also completed the second package. Items were removed from the scales that misfit the Rasch model (Chi2 p > 0.05), were redundant or displayed differential functioning by gender. Rasch analysis confirmed two unidimensional scales (p < 0.05); activity limitations (11 items) and QoL (27 items). Internal consistency was good for both scales (0.93 and 0.91) as was test-retest reliability (0.89 and 0.91 respectively). The CLIQ scales were related (as expected) with the NHP section scores and the U-FIS. It was interesting to note that QoL scores were related to both physical and emotional impairments. Conclusion The CLIQ is the first scientifically rigorous PROM designed specifically for CD patients. It consists of two unidimensional scales with excellent psychometric properties. It should prove to be a valuable tool for evaluating the impact of CD and its treatment from the patients’ perspective. Disclosure of Interest None Declared

P182 - Patient perceptions of home biologic therapy – adalimumab

Background: In the Danish Crohn Colitis Database during the treatment era of 5-Aminosalicylic acid (5-ASA), steroids and surgery, it has been revealed that 8 years from diagnosis 44% of Crohn’s disease (CD) patients were characterized with a mild disease course, 20% with an aggressive (relapse every year) and 36% with a moderate disease course (relapse every other year). Aim: The outcome of the first treatment course with 5-ASA monotherapy (1.5 4.8 g/day) was retrospectively studied in a consecutive cohort of 345 patients with CD diagnosed 1952 2007. The immediate and long-term outcome of 5-ASA treament was described. Methods: A phenotyped model was used to assess treatment response: Immediate outcome (30 days after the start of 5-ASA) was defined as Complete response: Total regression of symptoms. Partial response: Improvement of symptoms. No response: No regression of symptoms with a need to shift from 5-ASA to an immunomodulator or surgery. Longterm outcome (irrespective of the length of the treatment) was defined as: Prolonged response: Still in complete/partial remission 1 year after induction of remission (either maintained on or after cessation of 5-ASA). 5-ASA dependency: Relapse on stable/reduced dose of 5-ASA requiring dose increase to regain remission or relapse within 1 year after 5-ASA cessation regaining complete/partial response after 5-ASA reintroduction. Results: One hundred sixty-five (48%) out of 345 patients had monotherapy with 5ASA. In 50% of them 5-ASA was initiated within one year of diagnosis with a range 0 49 years. Complete or partial response was obtained in 75% and no response in 25% of patients within 30 days of treatment. Among initial responders (complete/partial response), prolonged 5-ASA response was obtained in 47% (59) of patients, 5-ASA dependency in 31% (38) and 18% (22) of patients lost initial response to 5-ASA and had to shift to surgery (73%) or immunomodulator (27%). Five patients (4%) were not assessed in long-term outcome due to short treatment couse. Female gender was associated with higher probability to develop prolonged response or 5-ASA dependency (OR 2.68, 95%CI: 1.06 6.77, p = 0.03). The median duration (range) of 5-ASA course was 34 months (1 304) in prolonged responders, 63 (6 336) in 5-ASA dependent and 5 (2 10) in non-responders. Conclusion: Patients with CD may profit from 5-ASA treatment. Seventy-eight percent of initial responders obtained long-term benefit with 31% becoming 5-ASA dependent, resulting in 5 up to 28 years of remission on 5-ASA in 50% of them. Prospective studies are warranted to assess the role of 5-ASA in CD.

Systematic review: advice lines for patients with inflammatory bowel disease

Abstract Objective: Advice lines for patients with inflammatory bowel diseases (IBD) have been introduced internationally. However, only a few publications have described the advice line service and evaluated the efficiency of it with many results presented as conference posters. A systematic synthesis of evidence is needed and the aim of this article was to systematically review the evidence of IBD advice lines. Materials and methods: A broad systematic literature search was performed to identify relevant studies addressing the effect of advice lines. The process of selection of the retrieved studies was undertaken in two phases. In phase one, all abstracts were review by two independent reviewers. In phase two, the full text of all included studies were independently reviewed by two reviewers. The included studies underwent quality assessment and data synthesis. Results: Ten published studies and 10 congress abstracts were included in the review. The studies were heterogeneous both in scientific quality and in the focus of the study. No rigorous evidence was found to support that advice lines improve disease activity in IBD and correspondingly no studies reported worsening in disease activity. Advice lines were found to be health economically beneficial with clear indications of the positive impact of advice lines from the patient perspective. Conclusion: The levels of evidence of the effect of advice lines in IBD are low. However, the use of advice lines was found to be safe, and cost-effective. Where investigated, patients with IBD overwhelmingly welcome an advice line with high levels of patient satisfaction reported.

PWE-008 Clinical outcomes of ustekinumab in resistant crohn’s disease: UK IBD tertiary referral centre ‘real-world’ experience

Introduction Ustekinumab (UST) binds to the p40 subunit of IL12 and IL23 to prevent IL12RB1 cell-surface receptor activation and thus inhibits downstream inflammatory signalling. It is approved for moderately to severely active Crohn’s disease (NICE TA456). We assessed the clinical outcomes and safety of UST in a ‘real-world’ cohort of refractory Crohn’s disease patients treated at a single UK centre. Methods We retrospectively collected data from the electronic records of Crohn’s disease patients treated with UST at a single UK IBD tertiary referral centre. Patient demographics and adverse events were recorded. Clinical response to UST was evaluated at baseline and follow up using Harvey-Bradshaw Index (HBI) scores, C reactive protein (CRP), and faecal calprotectin (FC). Paired Student’s T Tests were used to determine statistical significance. Results 26 patients (mean age 36 years; age 18–62 years; M:F ratio=1:1.6) with a variety of Crohn’s disease phenotypes (L1=8; L2=6; L3=12) were treated with UST. 9 patients (35%) had stricturing disease and 5 patients (19%) penetrating disease. All patients had failed at least one anti-TNF agent. 15 patients (58%) had failed two anti-TNF agents, and 11 (42%) had failed an anti-TNF and subsequent vedolizumab therapy. 7 patients (27%) received immunomodulatory co-therapy (AZA=5; MTX=2), and 11 (42%) received bridging steroids. 12 week data was available for 20 patients. At 12 weeks, mean HBI significantly improved (5 vs 9; p<0.05). There was reduction in mean FC (763 vs 1026; ns), but no change in mean CRP (14 vs 11; ns). 10 patients (50%) demonstrated subjective and objective (FC +/-CRP +/- endoscopic) response to therapy. 6 of these patients received bridging steroids, of which all had reduced and 4 had completed their steroid course. Of all treated patients 2 discontinued UST (recurrence of a transitional cell carcinoma; primary non-response to therapy requiring surgery), and side effects were reported in 2 patients (Bell’s Palsy; lower respiratory tract infection). Conclusions UST appears clinically effective and safe in this cohort of treatment-refractory Crohn’s disease patients after 12 weeks of therapy. Future work to combine ‘real world’ data and to assess longer term outcomes will help us to better understand and place the use of UST in the management of Crohn’s disease.

A real-world, long-term experience on effectiveness and safety of vedolizumab in adult patients with inflammatory bowel disease: The Cross Pennine study

BACKGROUND Real-life data on vedolizumab effectiveness in inflammatory bowel disease (IBD) are still emerging. Data on the comparative safety of the gut selective profile are of particular interest. AIMS To assess clinical outcome and safety in IBD patients treated with vedolizumab. METHODS We retrospectively collected data of patients treated with vedolizumab at eight UK hospitals (August 2014-January 2018). Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Possible predictors of clinical response were examined. RESULTS Two hundred and three IBD patients (mean treatment 16 ± 8 months) were included. Of these, 135 patients (mean age 40.6 ± 16.0 years; F:M 1.9:1) had CD and 68 (mean age 44.5 ± 18.1 years; F:M 1:1.2) had UC. According to PGA, 106/135 (78.5%) CD and 62/68 (91.2%) UC patients (p = 0.02) had a clinical response/remission at 14 weeks, whereas 76/119 (63.9%) CD and 52/63 (82.5%) UC patients (p < 0.01) showed a sustained response or remission at 52 weeks, with a high adherence rate (97%). No predictors of clinical response were found. The cumulative incidence of infectious diseases was 11.9 per 100 person-years. CONCLUSION Vedolizumab is an effective therapy for inducing and maintaining remission of IBD, with better results for UC, and with a good safety profile.