bluuebunny/crossref_metadata_2025_split huggingface dataset:
P609 An IBD dermatology multidisciplinary clinic: A single tertiary centre experience
Authors: Levy N , Matz H , Maharshak N , Waizbard A 
Published: January 2020

Abstract

Background
Dermatologic manifestations of inflammatory bowel disease (IBD) are common and cause a significant burden on patients’ quality of life. More than 10% of IBD patients present cutaneous manifestation at the time of diagnosis; however, less than one in 10 IBD patients seeks dermatologic care. In up to 30% of cases, intense skin reactions mandate treatment discontinuation. There is growing evidence that the treatment of IBD patients improves when given by a multidisciplinary team yet data on combined IBD dermatology clinics is scarce. The aim was to describe our experience in this approach.

Methods
A retrospective descriptive study of a 2-year multidisciplinary IBD-dermatology clinic in a tertiary hospital in Israel, performed by an IBD expert and a senior dermatologist.

Results
Eighty-six visits (52 patients, of whom 50% males) were documented. Patients included Crohn’s disease (n = 41) and ulcerative colitis (n = 11) at an average age of 43.1 ±16.1 years. Rash was the most common referral aetiology, accounting for 60.4% (52/86) of clinic visits. A preexisting skin disorder occurred in 65.3% (34/52) of patients. Psoriasis, the most common diagnosis, was diagnosed in 19 patients. Additional extra-intestinal manifestations occurred in 38.4% of patients (20/52). Majority of patients, 92.3% (48/52), were under medical treatment: 77% (40/52) of the cohort received biologic therapy, mostly (61.5%) anti-TNFα agents
Visits included preventive measures (mole assessment), diagnostic tests (skin biopsy) and therapeutic procedures (needle cauterisation, phototherapy). In 65.1% (56/86) of visits– topical treatment was advised. Among 21 re-visits, skin improvement was observed in 57.1%. Treatment-related skin symptoms were suspected in 34.6% of patients (18/52): in 38.8% (7/18), biological treatment was changed and in 13 patients, topical therapy was added, resulting in dermatologic improvement in 12 patients.

Conclusion
The IBD-dermatology clinic appears to improve IBD patient care. This clinic sets a new standard of treatment for IBD patients with dermatological issues
P614 Micro-fragmented autologous adipose tissue injection for fistula-in-ano (MAATIFA) in patients with Crohn’s disease: A prospective observational study
Authors: Sturiale A , Fabiani B , Cafaro D , Menconi C , Celedon Porzio F , Franceschi M , Naldini G 
Published: January 2020

Abstract

Background
The use of adipose-derived mesenchymal stem cells showed great regenerative properties. They were used in several surgical fields such as plastic, orthopaedic and colorectal surgery with good results. It was recently published their efficacy to treat Crohn-related anal fistula but they were obtained through a laboratory process with significant costs. The aim of the study is to evaluate the effect of the micro-fragmented autologous adipose tissue injection associated with the advancement flap for the treatment of Crohn-related complex perianal fistula in one surgical step.

Methods
From January 2017 to February 2018 all the patients that fulfil the following criteria were enrolled in the study. Inclusion criteria were Crohn-related complex anal fistula confirmed by pelvic magnetic resonance or 3D-360° transanal ultrasound, fistula drained with a seton from 4 to 6w, first sphincter-saving procedure. The harvested fat from the abdominal wall was processed using the Lipogems® kit (Figure 1). The internal opening was closed through 2/0 PDS stiches with mucosal flap above it. The final product was then injected around the internal opening and fistula tract previously debrided (Figure 2 and 3).

Outcomes were determined at 1-3-6-12 months follow-up assessing success rate, defined as clinical remission without any discharge.

Results
Ten patients underwent the procedure in the time interval between two biologic drug administration (6 infliximab –4 adalimumab). The homogenous follow-up was 12 months with an overall healing rate of 60%. No perioperative or postoperative complications were recorded.

Conclusion
Micro-fragmented autologous adipose tissue injection showed promising results to promote Crohn-related complex anal fistula healing. These good results are probably related to the reduction of inflammation and the activation of a reparative mechanisms.
P622 Recovery of nutrient deficiency as a predictor of remission in inflammatory bowel diseases
Authors: Iakovlev A A , Volkov A , Shcherbakova I , Leonova G , Piskovets V 
Published: January 2020

Abstract

Background
Development of nutritional deficiency (ND) due to the loss of nutrients, water and electrolytes with frequent stools, nutrients malabsorption, anorexia and increased catabolism is typical for patients with IBD relapse. To determine the frequency and structure of ND in patients with IBD relapse and to evaluate the therapeutic effect of nutritional support (NS) of nutritive mixtures during the course of therapy.

Methods
Two-phase three-step study with prospective monitoring in patients with IBD was conducted during 3 years in the period from 2010 to 2012. The first phase was carried out using a one-time screening scales MUST and NRS, further in phase 2, the NS structure was refined. 520 patients with IBD were examined: 410 with ulcerative colitis (UC) and 110 with Crohn’s disease (CD).

Results
The first, 2d and 3d degree of ND were detected in 111 (27.1%), 96 (23.4%) and 42 (10.2%) patients with UC, respectively. 2d and 3d degree of ND was recorded in 48 (43.6%) and 29 (26.4%) cases in patients with CD, respectively. At the second stage of the study, 80 patients with UC were randomised into two major groups, depending on the degree of NN, were divided into groups A (2d degree of ND) and B (3d degree of ND). On basic therapy, patients of the Ist group received a diet with a high amount of protein (HAPD) and increased calorage (2500 kcal/day), while to the patients of the IId group in addition to the basic therapy, nutritional mixtures: peptamen and modulen IBD (Nestle) in the amount of 1/3 of the daily calorage were prescribed. Efficacy of treatment was evaluated on the 3 d, 4th, 12th week. At the third stage of the study, during 3 years, the long-term results were studied using index of the relapse frequency (IRF). Pick of the IRF was in the first group and by the end of the study, it was 15 (75%) and 17 (85%) cases, respectively. In the second group IRF was significantly lower: 9 (45%) and 12 (60%) (p &lt;0,05).

Conclusion
In patients with UC and CD relapse ND of the first and 3d degree was recorded an average of 20.3% and 35%, respectively. The usе of NS provides a low-rate UC relapse, and thus stable remission of the disease.
P623 Cumulative incidence of infliximab use after a first flare of acute severe colitis
Authors: GHRIBI M , Mohamed G , Bizid S , Ben Sliman B , Boughoula K , Ben Abdallah H , Bouali R , Abdelli M N 
Published: January 2020

Abstract

Background
Since 2005, infliximab (IFX), an anti-tumour necrosis factor-α agent, has proven to be efficient as salvage and maintenance therapy for ulcerative colitis. In 2011, a randomised controlled comparative trial has demonstrated the short-term efficacy as a second-line treatment for acute severe colitis (ASC). Since then, few studies had evaluated the probability of first IFX use after a first flare of ASC. The aim of this study was to assess the cumulative incidence of IFX use after a first flare of ASC occurring after 2011.

Methods
Between June 2018 and January 2011, all inpatients with a first non-complicated flare of ASC were retrospectively randomised. Steroid resistance was concluded in patients undergoing colectomy or put into second-line medical therapy. Cumulative incidence of IFX use was evaluated by Fine and Gray model, considering colectomy and death as competing events.

Results
Twenty-five patients were reviewed (median age: 35y. (14-58y.); 11 females and 14 males). Thirty per cent of patients were active smokers. Only one patient had severe comorbidities. Half of the patients were admitted for an inaugural flare. A family history of an inflammatory bowel disease was noted in 12% of cases. sixteen per cent of patients had extraintestinal manifestations. At the moment of presentation, three-quarters of patients were not receiving any immunosuppressive therapy. Truelove and Witts criteria were present in 70% of cases. The average rates of CRP, plasmatic albumin and haemoglobin were respectively 131 mg/dl(43–260), 28 g/l (19–40), and 11g/dl (6,5-14). Sixty-four per cent of the patients responded to first-line medical therapy. Among patients with steroid-refractory colitis (9 patients), timely colectomy was performed in 1 case, 1 patient received cyclosporin (2mg/Kg per day) and 7 patients received infliximab (5mg/Kg on days 0, 14 and 42). Clinical response to second-line medical therapy was observed in 87% of patients. After a median follow- up period of 26 mo. (0,26-81 mo), 4 patients underwent colectomy: 2 urgent colectomies at the same hospitalisation and 2 subsequent colectomies for chronic active disease. Colectomy free survival rate at 5 years was 82%. Cumulative incidence of first infliximab use at 1 and 5 years was, respectively, 40% and 70%. In multivariate analysis, resistance to steroids (p = 0.0005) and history of thiopurines intake (p = 0.002) were significantly associated with subsequent use of IFX. No death was observed during the analysis period.

Conclusion
During follow-up, the vast majority of patients needed subsequent IFX use after their first flare of ASC.
P627 Acute severe ulcerative colitis in pregnancy: A retrospective cohort study
Authors: Ollech J , Avni-Biron I , Dalal S , Glick L , Schafer S , Pekow J , Cohen R , Rubin D , Sakuraba A 
Published: January 2020

Abstract

Background
Ulcerative colitis is a chronic inflammatory condition of the colon with peak incidence rates between the ages of 15 and 35 years. Consequently, women with ulcerative colitis are often diagnosed during childbearing years, which makes the effect of the disease on pregnant patients an important clinical question. Acute severe ulcerative colitis will affect up to 25% of patients. There are limited studies that describe the medical treatment, colectomy rates, and birth outcomes of women hospitalised with acute severe ulcerative colitis during pregnancy.

Methods
We performed a retrospective observational study of pregnant ulcerative colitis patients hospitalised at two large tertiary medical centres between January 2003 and December 2018. The primary endpoint was colectomy-free survival. Secondary endpoints included details of disease management and fetal outcomes.

Results
Twenty patients met the inclusion criteria. At admission, the median age was 30.3 years (IQR 23.4–32), and the median gestational age was 21 weeks (IQR 14–28). All patients met Truelove and Witts criteria for acute severe ulcerative colitis. The median follow-up time was 48 months (IQR 20.7–80). Colectomy free survival rates from admission were 90% at six months, 84% at one year, and 64% at four years (Figure 1). Only one patient (5%) underwent colectomy at her index admission. All patients were treated with intravenous steroids, and half received anti-tumour necrosis factor agents as inpatients (7 received infliximab and 3 received adalimumab). Following discharge, seven (35%) patients were maintained on infliximab, four (20%) were maintained on adalimumab, vedolizumab and azathioprine were used as the maintenance drug in one patient each, and another seven (35%) patients were transitioned to mesalamine preparations. Live birth occurred in 18 patients (90%), and the median gestational age at birth was 37 weeks (IQR 34.5–38). Adverse pregnancy outcomes included two spontaneous abortions (10%), six premature births (30%), and four low birth weight infants (20%). There were no stillbirths, and no major congenital abnormalities were noted.

Conclusion
We report on the largest cohort of pregnant patients hospitalised for acute severe ulcerative colitis and have shown that these patients have good response rates to standard treatments and comparable colectomy rates to studies of non-pregnant patients. In our cohort, there were relatively high rates of preterm and low weight births.
P633 Sustained reduction of IL-23-related cytokines IL-17A and IL-22 in a phase 2 study of mirikizumab in the treatment of patients with moderately-to-severely active ulcerative colitis through week 52
Authors: D’Haens G R , Sands B E , Kobayashi T , Tuttle J L , Schmitz J , Higgs R , Ho S , Sissons S E , Sandborn W J 
Published: January 2020

Abstract

Introduction
Interleukin (IL)-23 is a cytokine involved in the pathogenesis of ulcerative colitis (UC). Mirikizumab (miri) is a p19-directed IL-23 antibody that demonstrated efficacy and was well-tolerated in patients with moderate-to-severely active UC during 52 weeks (weeks) of a Phase 2 randomised clinical trial (AMAC, NCT02589665). Exploration of IL-23 pathway biomarkers supports an understanding of drug activity and mechanism of action. These analyses describe exploratory biomarker results in plasma for IL-23 pathway cytokines, IL-22 and IL-17A, in subjects that responded to miri induction treatment and continued with maintenance treatment up to Week 52.

Methods
Patients with moderately-to-severely active UC (Mayo score 6–12 with a minimum endoscopic subscore [ES] ≥2) were randomised 1:1:1:1 to receive intravenous placebo (pbo) (N=63), miri 50mg (N=63) or 200mg (N=62) with possibility of exposure-based (EB) increases, or fixed miri 600mg (N=61) every 4 weeks, with efficacy assessment at Week 12. Miri-treated patients who achieved a clinical response at Week 12 were re-randomised 1:1 into a double-blind maintenance period to receive miri 200mg subcutaneously every 4 weeks (Q4W; N=47) or every 12 weeks (Q12W; N=46), and were treated through Week 52. Plasma EDTA samples were collected at Weeks 0, 4, 12, 24, and week 52 to evaluate circulating levels of IL-17A and IL-22.

Results
Baseline (BL) characteristics of patients who entered the maintenance period were similar between groups. At BL, 52.7% had previously received a biologic. At Week 52, 46.8% of patients in the Q4W group and 37.0% in the Q12W group were in clinical remission. Initial reductions in median IL-17A and IL-22 plasma concentrations during the induction phase were observed in the combined miri re-randomised treated groups (50 mg, 200 mg, 600 mg to either 200 mg Q4W, or Q12W) with −86.2/−59.0 % change from BL to Week 12 in the 200 mg Q4W group and −141.1/−55.8 % change from BL in the 200mg Q12W group (Figure). At Week 52, further numerical reductions from Week 12 in IL-17A and IL-22 levels were observed with −74.4/−32.1% change from Week 12 in the 200 mg Q4W group and −69.8%/−47.7% change from Week 12 in the 200 mg Q12W group.

Conclusion
Patients treated with maintenance mirikizumab had further reductions in plasma levels of the IL-23-dependent pro-inflammatory cytokines, IL-17A and IL-22, beyond that initially observed in the induction phase. These data suggest sustained biologic activity of mirikizumab in patients with moderately-to-severely active UC during maintenance. Treatment with mirikizumab for 52 weeks leads to normal, or near normal (as observed in healthy volunteer plasma) circulating levels of IL-17A and IL-22.
P648 Efficacy including rapid response and safety of tofacitinib in Japanese patients with ulcerative colitis: A preliminary investigation in a specialised IBD centre
Authors: Watanabe K , Kawai M , Koshiba R , Fujimoto K , Kojima K , Kaku K , Kinoshita N , Sato T , Kamikozuru K , Yokoyama Y , Miyazaki T , Hida N , Nakamura S 
Published: January 2020

Abstract

Background
Genetic backgrounds and risk of herpes zoster or thrombotic adverse events differ between Western and Asian patients with ulcerative colitis (UC) treated with tofacitinib. We investigated the efficacy and safety of tofacitinib including the rapid response that showed treatment efficacy within ≤4 weeks among Japanese UC patients in our specialised IBD centre.

Methods
The study included 55 UC patients who were administered tofacitinib 5 or 10 mg twice daily and available for 16 weeks of efficacy and safety examination among 76 patients administered tofacitinib in our hospital. Efficacy was defined as a ≥2-point decrease in partial Mayo score (PMS) from baseline and remission with ≤1 MES coupled with no bloody stool.

Results
The patients’ age was 38.1±15.0 years, 21 patients were female, duration of disease was 92.7±88.0 months, baseline PMS was 5.2±1.9, white cell count was 7428±2631/µl, C-reactive protein was 1.1±1.7 mg/dl, and serum albumin was 3.9±0.6 g/dl. The last treatment just before tofacitinib administration was steroids (16.4%, 7 cases), anti-TNF agents (29.1%, 17 cases), and vedolizumab (1.8%, 1 case). The efficacy rate was 49.0% (23 cases; rapid responders) at 4 weeks and 74.5% (35 cases) at 16 weeks. Remission rate sequentially increased: 17.0% (8 cases) at 4 weeks, 27.7% (13 cases) at 8 weeks, and 49.0% (23 cases) at 16 weeks. No difference in remission rate was observed between anti-TNF-naïve patients (58.3%) and anti-TNF-treated patients (62.5%; p = 0.84). Additionally, immunomodulatory therapy-naïve patients exhibited a high response rate (80.0%). Moreover, 29.1% patients relapsed during maintenance therapy with 5 mg tofacitinib twice daily after achievement of remission with 10 mg tofacitinib twice daily. Basement PMS was significantly lower in the remission group (4.4 ± 1.7) than in the non-remission group (5.8 ± 1.8) at 16 weeks (p = 0.01). Receiver operating characteristic analysis identified 5.0 of basement PMS as a cut-off value to achieve remission at 16 weeks. Five cases (6.6%) of herpes zoster occurred. All cases were under treatment with tofacitinib 10 mg twice daily and had not been vaccinated. Fortunately, permanent damage was not observed after antiviral therapy. Three cases of fever and one case of leg oedema (as adverse events) recovered rapidly after tofacitinib was withdrawn. No thrombotic adverse event was observed despite the fact that 56.4% patients continued treatment with 10 mg twice daily after 16 weeks.

Conclusion
Approximately half of the included patients were rapid responders; sequential improvement within 16 weeks was observed. Tofacitinib was more effective in low-activity UC patients; its efficacy was not affected by history of treatment with anti-TNF agents.
P655 Pharmacokinetics of ustekinumab in children and adolescents with moderately to severely active Crohn’s disease: Results from UniStar, a phase 1 study
Authors: Adedokun O , Hyams J , Turner D , Griffiths A , Terry N , Padgett L , Jacobstein D , O’Brien C , Rosh J 
Published: January 2020

Abstract

Background
Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD) or ulcerative colitis. In the UniStar study, the pharmacokinetics (PK) of UST and its relationship with efficacy was evaluated in children who failed prior therapy. UniStar consisted of a PK portion (week 0–16) and extension (week 16–216); we report data through week 16.

Methods
UniStar is a multicentre, double-blind study (NCT02968108) designed to assess the PK, safety, and efficacy of UST in children (2–&lt;18 years) with moderately to severely active CD, Paediatric CD Activity Index (PCDAI) score &gt;30, and evidence of inflammation as measured by C-reactive protein &gt;3.0 mg/l or faecal calprotectin &gt;250 µg/g or ulcerations on ileocolonoscopy despite adequate treatment with corticosteroids and/or immunomodulators and/or anti-TNF therapies. Patients were randomised (1:1) and stratified by body weight (BW) and prior anti-TNF use for induction to one of 2 weight range-based IV doses: 130mg vs. 390 mg if BW ≥40 kg and 3mg/kg vs. 9 mg/kg if BW &lt;40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW &lt;40 kg. UST PK outcomes were assessed and compared with adult Phase 3 CD trials.

Results
44 patients (59% ≥40 kg; &gt;90% anti-TNF exposed) were randomised and treated with UST (n = 23 lower dose; n = 21 higher dose). Baseline demographics were generally similar between treatment groups. Most patients (67%) had a severe CD (PCDAI &gt;40). At weeks 0 (1 h after infusion), 3, 6, and 8, mean serum UST concentrations (SUC) in the lower- (51.3, 7.7, 3.0, 1.6 μg/ml) and higher-dose groups (149.0, 23.7, 9.1, 4.8 μg/ml) were generally dose proportional (Figure 1a). Following SC UST at week 8, the impact of the difference in induction doses had diminished by week 16 when mean SUC was 1.5 µg/ml in the lower-dose group vs. 1.8 µg/ml in the higher-dose group. In the overall paediatric population (combined doses), serum UST concentrations were comparable to those in the reference adult CD studies (Figure 1b and c). In the higher dose group, we observed a pattern toward lower mean serum UST concentrations in patients weighing &lt;40 kg vs. those weighing ≥40 kg; thus, UST should be dosed higher in patients &lt;40 kg. Overall at week 8 and week 16, more patients achieved clinical response (PCDAI reduction ≥15) and biomarker improvement with higher UST concentrations, although this pattern was not observed for clinical remission (PCDAI ≤10; Figure 2).

Conclusion
Overall, UST PK was generally comparable between paediatric and adult patients with CD. A trend towards better efficacy outcomes with higher UST concentrations was observed in children similar to adults with CD.