bluuebunny/crossref_metadata_2025_split huggingface dataset:
P699 The concordance of Short Form-36 Health Survey scores with Mayo scores in the tofacitinib ulcerative colitis clinical programme
Authors: Dubinsky M C , Bushmakin A G , Cappelleri J C , Woolcott J , Sharma P , Maller E , Salese L , Armuzzi A 
Published: January 2020

Abstract

Background
The Short Form-36 Health Survey version 2 (SF-36v2) is a generic health-related quality-of-life (HRQoL) instrument [1]. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In these exploratory analyses the concordance between total and partial Mayo scores and SF-36v2 scores was evaluated in patients with UC in the Phase 3 tofacitinib 8-week OCTAVE Induction 1&2 (NCT01465763; NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies.

Methods
A repeated measures regression model was used to evaluate the relationship between total and partial Mayo scores (as predictor) and SF-36v2 component and domain scores. A sensitivity analysis to assess the linearity assumption was performed using Mayo score as a categorical anchor (represented by integer values 0–12 [total] or 0–9 [partial]). Previous analyses identified clinically important differences (CIDs) in total and partial Mayo scores as changes of 3 points and 2.25 points, respectively [2]. Mean differences in SF-36v2 component and domain scores were compared with their recommended group-level CID thresholds [3].

Results
Clinically meaningful differences of 3 points and 2.25 points in total and partial Mayo scores, respectively, were generally associated with clinically meaningful differences in SF-36v2 component and domain scores, with the exception of Role-Emotional with partial Mayo score in the pooled induction studies and with total Mayo score in the maintenance study. In the induction studies, a 3-point difference in total Mayo score was associated with a mean difference exceeding CIDs in both the SF-36v2 Physical Component Summary score (mean improvement 4.5; 95% confidence interval [CI] 4.2, 4.7) and Mental Component Summary score (mean improvement 5.0; 95% CI 4.6, 5.3). Results were closely aligned when Mayo score was used as a categorical or continuous anchor, supporting a linear relationship between Mayo score and SF-36v2 scores (Figure). Similar results were observed in the maintenance study, and when assessing the relationship of partial Mayo score with SF-36v2 scores.

Conclusion
Clinically meaningful decreases in disease activity, as measured by Mayo score, were associated with clinically meaningful benefits in HRQoL, as measured by SF-36v2 component and domain scores. These findings highlight the impact that disease activity has on HRQoL and may assist with articulating the treatment effect of tofacitinib on specific domains.

References
P702 Treatment decisions in older inflammatory bowel disease patients: Applying gut feeling in an evidence-based era? A qualitative study
Authors: Waars S , Asscher V , Pieterse A , van der Meulen-de Jong A , Mooijaart S , Maljaars J 
Published: January 2020

Abstract

Background
The population of older patients with inflammatory bowel diseases (IBD) is increasing. Treating older patients is challenging as they are characterised by heterogeneity in geriatric domains, such as functional, social or mental status. Although treatment guidelines do not distinguish between older and adult patients with IBD, several studies have found a difference in applied treatment strategies. It is unknown which considerations contribute to this. Therefore, we performed semi-structured interviews with IBD gastroenterologists and IBD nurses to assess a) which patient characteristics they consider and b) which treatment goals they pursue in older IBD patients, compared with adult IBD patients and c) what view they have on prescribing IBD medications in older IBD patients.

Methods
IBD gastroenterologists and IBD nurses practicing throughout The Netherlands were asked to participate. Purposive sampling ensured a heterogenous population. Interviews took place in May or July 2019 were audio recorded and conducted face to face. Two researchers coded the verbatim transcripts independently. Codes and themes were obtained inductively and were finalised in consensus. Recruitment was stopped when no new information came out of three consecutive interviews.

Results
Ten gastroenterologists and five IBD nurses were included: eight females, median age 43 years (34–61), median years of experience in IBD care, eight years (1–20), three working in an academic centre. Comorbidity and polypharmacy were most frequently mentioned as important patient characteristics in the choice of treatment of IBD in older patients. Only when asked specifically, participants mentioned characteristics of frailty, of which self-dependence, mobility, and cognitive impairment most often. However, applying ‘a clinical view’ or ‘gut feeling’ were frequently mentioned and none of the participants assessed frailty systematically. Therapy goals in older patients differed from those in adult patients: participants indicated to pursue clinical remission more often than endoscopic remission. Most participants stated to be reluctant to prescribe thiopurines. Other opinions about preferred medication differed remarkably, especially regarding low dose prednisone maintenance therapy.

Conclusion
In the treatment of older IBD patients, attention is paid to comorbidity and polypharmacy, but geriatric characteristics, such as functional or cognitive impairment or frailty are barely taken into consideration. Clinicians put lower priority on pursuing endoscopic remission in older compared with younger patients. The large variation in clinicians’ treatment preferences reflects a lack of evidence regarding treatment of older patients with IBD.
P704 The biennial direct pharmaceutical costs per treatment with biologics for the inflammatory bowel disease in Greece: A comparative calculation study
Authors: Liatsos C , Papaefthymiou A , Kyriakos N , Giakoumis M , Tzouvala M , Doulberis M , Mavrogiannis C , Kountouras J 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD), as a chronic disease with relatively high prevalence worldwide, has undoubtedly resulted in a notable economic burden on health care systems globally. The IBD treatment with biologics (IBD-BT) seems quite complex with various strategies to induce and maintain remission and balance against long-term complications. IBD-BT costs have never been estimated in detail so far in Greece, especially during such a severe 10-years financial crisis experience.

Methods
Direct pharmaceutical costs for one and two years, both for induction and maintenance, adult treatment diagnosed with Crohn’s disease (CD-BT) or Ulcerative colitis (UC-BT) were estimated. For intravenous agents, the hospital drug prices and one day admission costs were calculated, whereas for subcutaneous biologics the retail ones. It was taken for granted that all patients were fully responders and after the approved induction scheme continued with the standard maintenance strategy. Prototype and biosimilar drug prices were also assessed where available. More specifically, when considering biosimilars, the most affordable one was included to our analysis. Each drug price was estimated based on the data collected from the 2019 Greek official electronic national publication on drug therapy of the Greek national organisation for medicines.

Results
Table shows the costs in euros of each IBD-BT scheme. The biosimilar adalimumab was proved as the most affordable choice both for CD- and UC-BT. The second most affordable choice for CD revealed to be the prototype Adalimumab and respectively for UC the recently introduced tofacitinib, in the maintenance dose of 5 mg bid after week 8 (with a slight burden when the more intensive scheme with Tofacitinib 10 mg bid for 16 weeks is necessary). The most expensive strategies include Ustekinumab 90 mg (per 8 weeks for body weight—BW &gt; 55 to ≤85 kg and &gt;85 kg) and the prototype Infliximab 5 mg/kg (per 8 weeks for BW&gt;81 kg), whereas Vedolizumab remains expensive regardless BW. It is worthwhile to mention that the hospitalisation expenditures (563€) raise the costs of intravenous agents when compared with the subcutaneous ones.

Conclusion
The biennial direct pharmaceutical costs for the approved IBD-BT schemes both for induction and maintenance phases in fully responders were estimated thoroughly for the first time in Greece. These results should motivate Governments and European Union policymakers in order to promote cost-benefit and cost-utility studies to offer the best patients’ benefit by evaluating and deciding the most suitable regimen with respect to biologic prices, adverse effects, hospitalisation expenditures, IBD complications and recurrences.
P707 Anti-TNFα therapy has no effect on bone mineral density in younger patients with inflammatory bowel disease: A single-centre observational study
Authors: Filip R , Jarmakiewicz - Czaja S , Piątek D , Sztembis J , Pękala A , Guz W 
Published: January 2020

Abstract

Background
Active inflammation negatively affects bone mineral density. Biological treatment, among others silences the excessive reaction of the immune system, which can also reduce the risk of osteoporosis. The aim of the study is to determine whether bone mineral density is higher in patients with biological therapy.

Methods
In total, 112 patients over 18 years of age with CD (Crohn’s Disease) or UC (Ulcerative colitis) were included in the study. The mean value age was 35 years. Patients who had received anti-TNFα therapy (biosimilar infliximab CT-P13 or adalimumab), and who underwent densitometric evaluation after two year treatment, were selected. Those who had never received anti-TNFα therapy were selected as controls. Information regarding age, sex, weight, duration of CD, use of glucocorticoids and bisphosphonates, and signs of disease activity at the time of densitometric measurement were collected. Bone mineral density was measured by dual-energy X-ray absorptiometry (DEXA) within femoral neck and lumbar spine. Results are reported as g/cm2 and presented either as Z-score or as a T-score.

Results
The study group has characterised a mean value BMI (Body Mass Index)—24. The group of patients with anti-TNFαα therapy showed an average T-score left femur −0.7744 (CD) and −0.4382 (UC), but without anti-TNFα therapy −0.6636 (CD) and −0.2208 (UC). The entire study group showed a mean value t-score left femur of −0.54286. There were no significant statistical differences between the examined groups and the effect of anti-TNFα therapy on BMI, T-score left femur, T-score L2–L4

Conclusion
The results of the preliminary study assessing the effect of anti-TNFα therapy on bone mineral density among the two treatment groups (CD and UC) do not indicate significant differences after the introduction of such therapy
P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results
Authors: Viola A , Fiocco G , Alibrandi A , Macaluso F S , Cappello M , Privitera A C , Magrì G , Garufi S , Centritto A , Ventimiglia M , Giuffrida E , Ferracane C , Costantino G , Renna S , Orlando A , Fries W 
Published: January 2020

Abstract

Background
Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients.

Methods
Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP).

Results
One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p &lt; 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1).

Conclusion
Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.
P722 Upadacitinib was not associated with anaemia in patients with moderately to severely active ulcerative colitis: Results from the U-ACHIEVE study
Authors: D’Haens G , Hebuterne X , Higgins P D R , Loftus- E V , Zhou W , Lacerda A P , Xie W , Liu J , Danese S 
Published: January 2020

Abstract

Background
Anaemia is a frequent complication in patients with Crohn’s disease and ulcerative colitis (UC), and patients who respond to treatment generally show improvement in anaemia. Decrease in haemoglobin (Hgb) levels and anaemia may be associated with Janus kinase (JAK) inhibitors. Upadacitinib (UPA), an oral JAK1 selective inhibitor, has demonstrated favourable dose-dependent efficacy in patients with moderately to severely active UC.1 This analysis of data from the U-ACHIEVE study addressed effects of UPA treatment on Hgb levels in patients with UC.

Methods
U-ACHIEVE (NCT02819635) was a randomised, double-blind, placebo (PBO)-controlled phase 2b clinical trial. Adults with moderately to severely active UC were randomised to receive 7.5, 15, 30, or 45 mg UPA or PBO once daily (QD) for 8 weeks. Hgb levels were measured for all groups at baseline (BL) and weeks 2, 4, 6, and 8. Mean change from BL was calculated for each group. p-values for comparison between UPA and PBO groups were calculated using one-way ANOVA; no multiplicity adjustment was applied. Percentage of patients with Hgb values grade 2 (15–20 g/l Hgb decrease from BL), grade 3 (&lt;80 g/l Hgb level or 21–29 g/l Hgb decrease from BL), and grade 4 (&lt;70 g/l Hgb level or &gt;29 g/l Hgb decrease BL) anaemia were determined for all treatment groups using the Common Terminology Criteria for Adverse Events version 5. Adverse events (AE) were reported by investigators.

Results
Included in the analysis were 250 patients (mean age ± SD, 42.3 ± 14.2 years; disease duration, 8.2 ± 2.5 years). At BL, most treatment groups had similar mean Hgb levels, except for the 15 mg UPA group, which had significantly lower Hgb levels vs. PBO group (Table). Increased or stable mean levels of Hgb at week 8 vs. BL were observed in most UPA treatment groups. The PBO group had the greatest decrease in Hgb vs. BL at week 8 compared with UPA treatment groups (Figure). Grade ≥2 anaemia was reported in 17.4% of patients receiving PBO and 14.4% of all patients receiving UPA (14.9%, 12.2%, 12.0%, and 17.9% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). Grade ≥3 anaemia was reported in 8.7% of patients receiving PBO and 5% of all patients receiving UPA (6.4%, 6.1%, 6.0%, and 1.8% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). One subject receiving 7.5 mg QD UPA had grade 4 anaemia. AE of anaemia was reported in 6.5% of patients receiving PBO and in 2.1%, 8.2%, and 3.8% of patients receiving 7.5, 15, and 30 mg UPA, respectively, but not in the 45 mg UPA group.

Conclusion
Decreased Hgb levels over time were observed more frequently in the PBO group. The maintenance of Hgb levels in patients receiving UPA was likely because of improvement of underlying UC.

Reference
P727 Small bowel capsule endoscopy impact on therapeutic decisions in established Crohn’s disease: Analysis of a real-world data
Authors: Gómez E J , Gonzalez R A , Pereyra L , Mella J M , Panigadi G N , Fischer C , Roel M , Cimmino D G , Pedreira S , Boerr L A 
Published: January 2020

Abstract

Background
Small bowel (SB) evaluation in established Crohn’s disease (eCD) is of paramount importance for planning therapy strategies. However, the utility of CE in helping physicians to make decisions in eCD is not currently well established. To investigate clinical impact of CE to assess activity and extension of eCD and to evaluate whether the results of CE modify therapeutic decisions.

Methods
We conducted a single centre retrospective cohort study. All consecutive adult’s patients submitted to CE for eCD were included from November 2012 to November 2018. Data on demography, previous research, medications for IBD and follow-up were analysed. Univariate analysis was carried out to identify CE features associated with changes in therapeutic management.

Results
A total of 329 CE protocols in adult′s patients were performed, of which 90 were in IBD. We included in the analysis 27 CEs submitted for eCD. The mean age was 35 years (range 15–75), 17 (63%) were males and median disease duration was 8 years. The CE reached the cecum in 26 cases (96%) and retention was observed in only one patient (4%) without necessity of surgical removal. At the time of CE, 5 patients (18%) had abnormal inflammatory biomarkers, anaemia in 4 (15%), abdominal pain in 18 (67%) and diarrhoea in 16 (59%). Thirteen of 27 patients (48%) had CE findings consistent with mucosal activity of CD. The lesions identified by CE included ulcers 11 (41%), erythema and villous enema 10 (37%), erosions 2 (7%), stenosis 2 (7%) and were distributed mainly in the distal part of the SB (3rd tertile) in 12 (44%), but in 4 (15%) the proximal SB (1st and 2nd tertile) was also affected. The mean Lewis Score (LS) was 784 (8–5392). Significant inflammatory activity (LS ≥ 135) was detected in 9 (33%) and was moderate or severe (LS &gt; 790) in 2 (7%). CE has changed Montreal classification in 4 (15%) of patients and in 14 (52%) SB mucosal activity was ruled out. Indeed, CE has changed therapeutic management in 14 (52%) of patients within 3 months after the CE, as follows: 8 patients were started new biological therapy, 3 were optimised biological therapy, 2 were started on budesonide and 1 suspended azathioprine. Proximal SB affected, as compared with only distal SB affected, were more frequently associate with changes in therapeutic management (100% vs. 43%, p: 0.04). Significant inflammatory activity (LS ≥ 135), as compared with LS &lt; 135, were also more frequently associate with changes in therapeutic management (82% vs. 25%, p: 0.004).

Conclusion
In our study, CE in patients with eCD added valuable clinical information and had a great impact on therapeutic decisions. Whether this approach will improve outcomes in eCD will require further investigation.
P728 Comparative assessment of faecal microbiota transplantation and current therapies as induction treatment for active refractory ulcerative colitis: A systematic review and network meta-analysis
Authors: Malandris K , Paschos P , Koukoufiki A , Katsoula A , Manolopoulos A , Tsapas A , Bekiari E 
Published: January 2020

Abstract

Background
Emerging evidence suggests that faecal microbiota transplantation (FMT) can induce remission in patients with refractory to standard treatment ulcerative colitis (UC).

Methods
We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of FMT and current therapies as induction treatments in UC. We searched Medline, Embase, CENTRAL and grey literature sources up to October 2019. We included randomised controlled trials of patients with active UC that compared FMT, infliximab, adalimumab, golimumab, vedolizumab and tofacitinib to each other or placebo. Efficacy outcomes were clinical remission and response. Safety outcomes were incidence of any adverse event (AE), serious AEs and infections. We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities.

Results
Twenty trials (5177 patients) were included in the analysis. There was only one head to head RCT (vedolizumab vs. adalimumab). FMT was superior to placebo for induction of clinical remission (OR 2.80; 95% CI 1.50–5.23) and response (OR 2.53; 95% CI 1.53–4.20). No indirect comparisons between FMT and licensed treatments reached statistical significance for efficacy outcomes. On SUCRA analysis, FMT (SUCRA 0.57, 0.58) had comparable SUCRA values with golimumab (SUCRA 0.53, 0.39) and vedolizumab (SUCRA 0.58, 0.61) in terms of clinical remission and response respectively. Infliximab (SUCRA 0.71, 0.93) and tofacitinib (SUCRA 0.85, 0.75) were ranked highest while adalimumab (SUCRA 0.23, 0.21) was ranked lowest. There was no increase in the rates of any AEs for FMT and licensed therapies and no differences in indirect comparisons. Vedolizumab (SUCRA 0.81) was the safest option, followed by tofacitinib (SUCRA 0.55). FMT (SUCRA 0.38) had comparable SUCRA values with adalimumab (SUCRA 0.37) and golimumab (SUCRA 0.47). Only tofacitinib increased the incidence of infections compared with placebo (OR 1.51; 95%CI 1.05–2.19). Based on SUCRAs, FMT (SUCRA 0.83) was the safest in terms of infections. Vedolizumab had lower incidence of serious AEs compared with FMT and placebo, while FMT was ranked as the least safe treatment. In subgroup analysis, FMT through the lower gastrointestinal (GI) tract was superior to placebo (OR 3.92; 95%CI 1.94–7.92) and performed numerically better than FMT through the upper GI tract (OR 0.29; 95%CI 0.08–1.13).

Conclusion
Evidence suggests that FMT could be an efficacious and safe alternative induction therapy for refractory UC. Lower GI delivery of FMT might be more effective. Due to the absence of head-to-head trials and the limited size of FMT trials, conclusions must be interpreted with caution.
P734 Should we have a higher threshold for anti-TNF serum levels in Crohn’s disease patients with perianal disease?
Authors: Arieira C , Dias de Castro F , Cúrdia Gonçalves T , Moreira M J , Cotter J 
Published: January 2020

Abstract

Background
Tumour necrosis factor (TNF) inhibitors are potent drugs effective for the treatment of both luminal disease and perianal fistulas in Crohn’s disease (CD). Recently, there is some evidence that patients with perianal disease might need higher concentrations of anti-TNF levels compared with patients without perianal disease. The aim of this study was to compare anti-TNF serum concentrations: IFX (infliximab) or ADA (adalimumab) between patients with active and closed perianal fistulas with CD.

Methods
Retrospective study including that was on anti-TNF for at least 6 months. Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging/ultrasound.

Results
We included 55 patients with CD and perianal disease, 54.5% males, median age of 31 (interquartile range: 18–71) years. Forty-two were on IFX and 13 on ADA. Median IFX serum concentrations [IQR] were higher in patients with closed fistulas (n = 19) compared with patients with actively draining fistulas (n = 23): 7.7 mg/ml [0–32.6] vs. 1.5 mg/ml [0–9.5], respectively (p &lt; 0.001). A similar difference was seen in patients treated with ADA: median serum concentrations were 9.6 mg/ml [6–21.9] in 10 patients with closed fistulas vs. 4 mg/ml [4–4.3] in 3 patients with producing fistulas, p = 0.007. Serum concentrations superior or equal to 4.68 mg/ml for IFX (AUC of 0.87; 95% CI: 0.73–0.96) were associated with fistula closure.

Conclusion
Higher serum levels of anti-TNF drugs were associated with perianal fistula closure. Patients with CD and perianal disease may benefit from intensification of biological therapy.