bluuebunny/crossref_metadata_2025 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

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

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

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 <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

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

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

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

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

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–<18 years) with moderately to severely active CD, Paediatric CD Activity Index (PCDAI) score >30, and evidence of inflammation as measured by C-reactive protein >3.0 mg/l or faecal calprotectin >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 <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 <40 kg. UST PK outcomes were assessed and compared with adult Phase 3 CD trials.

Results

44 patients (59% ≥40 kg; >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 >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 <40 kg vs. those weighing ≥40 kg; thus, UST should be dosed higher in patients <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.
P657 Evolution of Crohn’s disease progression and surgery rates over 10 years for patients who initiated biologic treatment early compared with late or no biologic initiation
Authors: Pillai N , Dusheiko M , Maillard M , Michetti P , Pittet V
Published: January 2020

Background

This study aimed to evaluate the clinical outcomes for adults diagnosed with Crohn’s disease (CD) who started biologic treatments within 2 years of diagnosis (early initiation) compared with those who started biologics >2 years after diagnosis or who did not receive any biologic treatment during the period of observation (late/no biologic initiation).

Methods

We conducted a retrospective analysis using 10 years of follow-up data from patients included in a national cohort study. We used propensity score methods to match patients in the early vs. late/no biologic initiation groups based on key baseline patient and clinical characteristics. Kaplan–Meier time-to-event models were used to evaluate the risks of intestinal resection surgery, fistula, stricture, and disease flares for each group. In addition, a subgroup analysis was performed stratifying patients known to have initiated biologic treatments into early (≤2 years after diagnosis) vs. late (>2 years after diagnosis) initiation groups.

Results

In total, 411 patients were matched in the early initiation (n = 230) vs. late/no initiation (n = 181) groups. Two years after diagnosis, early biologic initiators had a 12% lower probability of intestinal resection surgery, a 9% higher probability of disease flares and fistulae, and a 5% higher probability of strictures compared with the late/no biologic initiators (Figure 1). After 10 years, the overall difference in the cumulative probability for each event were not statistically significant between the two groups. In the subgroup analysis, patients who initiated biologics early had a lower overall probability of stricture (p < 0.01), disease flares (p < 0.01), and intestinal resection surgery (p = 0.72), and a higher probability of fistula (p = 0.74) 10 years after diagnosis when compared with the group of patients who initiated biologics late.

Conclusion

This study found no significant differences in the long-term cumulative probabilities of intestinal resection surgery, fistula, stricture, and disease flares amongst CD patients who initiated biologic treatment early compared with similar patients who initiated biologic therapy late or who had not started any biologic treatments. However, in a subgroup of patients known to receive biologic treatments, early initiation was associated with significantly lower overall risks of strictures and disease flares. These results highlighted the need for more individualised care in CD in order to target aggressive treatment approaches to patients who show early signs of a complicated disease course.
P660 Evaluating the effectiveness of disease assessment at 2 weeks following a course of oral steroids: Does early intervention affect outcomes?
Authors: Slater J , ALGIEDER A , Jones J , Bates B , De Silva S
Published: January 2020

Background

Early intervention in those patients not responding to a course of oral steroids following an Acute flare of their IBD is essential for improved outcomes. It enables re-assessment and escalation of treatment in those that are non-responders. We present our data on the effectiveness of an IBD nurse-led telephone follow-up appointment two weeks after commencing a course of oral steroids and its impact on outcomes.

Methods

Data collected prospectively on all patients treated with oral prednisolone between March and November 2019. Partial Mayo score for ulcerative colitis (UC) and clinical assessment of symptoms for Crohn’s disease (CD) patients were used to assess response to treatment at 2 weeks.

Results

57 patients were treated with a Prednisolone reducing regime during the 8 months period. Patient demographics included 27 males and 30 females,19 CD and 38 UC patients with a median age of 48 (range 16–88). Following 2 weeks of treatment, 54% (31) of patients reported an improvement in symptoms-19 UC patients (Partial Mayo 0–4) and 12 CD patients. However, 45% (26) patients did not have a clinical improvement at week 2, 19 UC (Partial Mayo 2–9) and 7 CD were still symptomatic. In those patients who had not responded 3 were commenced on Azathioprine, 6 on Methotrexate and one patient had a slow response to steroids. Seven patients were escalated to receive biological therapy (3 vedolizumab, 2 infliximab, 1 ustekinumab and 1 adalimumab). Two other patients had their dose of vedolizumab increased, one patient was switched to another class of biologics. Three patients had a Flexible Sigmoidoscopy and following that 2 were admitted to receive IV steroids and escalated to biological therapy and Methotrexate. One patient was directly admitted for biological therapy, and 2 patients had an alternative diagnosis of Bile Salt Malabsorption which was treated. At the 3 months follow-up period all patients were well and had avoided further admissions or surgery, with only one patient electively opting for surgery.

Conclusion

Our data show that following a course of oral steroids for a flare of IBD, 45% are still symptomatic after 2 weeks. In this cohort, optimisation of treatment occurred in 23 patients (88%) with either the introduction of biological agents, or early introduction of immunomodulatory therapy. We believe that These data supports the implementation of an early review with appropriate intervention, demonstrating improved patient outcomes.
P666 Neutropenia in inflammatory bowel disease patients on TNF inhibitors: A single-centre, retrospective cohort study
Authors: AlAskar D , Mais A , Al Sulais E , Alameel T
Published: January 2020

Background

Tumor necrosis factor-α inhibitors (TNFi) have become the mainstay of treatment in moderate to severe cases of IBD.

The haematological safety profile of these agents has been documented in multiple clinical trials and post-marketing registries. Nonetheless, neutropenia has been reported in patients receiving TNFi for IBD and other diseases (Bessissow et al 2012).

In this study, we aim to ascertain the relationship between the use of TNFi and the development of neutropenia in IBD patients.

Methods

This is a retrospective cohort study including all adult IBD patients receiving TNFi at our centre from the year 2007 to 2018. Our primary outcome was the development of any neutropenic episode after starting a TNFi. Neutropenia was defined as circulating absolute neutrophil count (ANC) less than 1500/mm3.

For our secondary outcomes, we evaluated the impact of concomitant use of (5-ASA) or an immunomodulator on the risk of developing neutropenia. We also looked at the effect of baseline neutrophil and WBC counts on the subsequent development of neutropenia.

Results

A total of 292 patients met the inclusion criteria, 11 patients were excluded for not having neutrophil count done. The final analysis included 281 patients. The mean age of patients in this study was 33. Adalimumab was the most frequently prescribed TNFi. Of those included, 96 patients (34.2%) developed at least one episode of neutropenia while on a TNFi. The majority of these episodes (67.7%) were mild with ANC between 1000 and 1500/mm3. There was no significant difference in the age, gender, agent used or type of IBD between those who developed neutropenia and those who did not. On the other hand, baseline neutrophil count and concomitant use of azathioprine and 5-ASA were significant independent predictors of neutropenia after commencing TNFi. (Table 1).

Conclusion

In this study, mild neutropenia was common amongst IBD patients on TNFi. Patients were more likely to develop neutropenia if they have been on concurrent therapy with an immunomodulator or 5-ASA. Future prospective studies are required to further clarify the significance of neutropenia in IBD patients receiving TNFi.
P668 Real-life comparison of different anti-TNF biologic therapies for ulcerative colitis treatment: A retrospective cohort study
Authors: Barberio B , Zingone F , D’Incà R , Marinelli C , Maccarone M C , Gubbiotti A , Cingolani L , Lorenzon G , Ghisa M , Savarino E V
Published: January 2020

Background

Currently, ulcerative colitis (UC) can be treated with different anti-Tumor Necrosis Factor (TNF) drugs, which selection is mainly based on physician’s perspective. Indeed, head-to-head comparison studies evaluating the effectiveness and tolerability of anti-TNF drugs are lacking. The aim of this study was to compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate to severe UC.

Methods

Retrospectively, 122 UC patients treated with Infliximab (IFX) Originator and Biosimilar, Adalimumab (ADA) and Golimumab (GOL) were included. We performed an intention to treat analysis to evaluate the clinical response, clinical remission, steroid-free clinical remission and endoscopy response according to the different time-points of the follow-up (ie. after induction, at 30 and 52 weeks). Baseline and post-induction predictor factors of these outcomes were evaluated using multivariate logistic regressions models. Data were analyzed using STATA11 software.

Results

Overall clinical response was 79.5% after induction, 79.5% at 30 weeks, 75.4% at 52 weeks, while the overall steroid-free clinical remission was 42.6%, 45.1%, 55.7%, respectively. After induction, a higher rate of treatment failure was observed in GOL group. Moreover, at the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL (38.7% and 54.8% with p = 0.006 and p = 0.003, respectively). At week 52, endoscopic response was achieved by 46.5% of the population (IFX Originator: 46.7%; IFX Biosimilar: 40%; ADA: 51.6%; GOL: 22.6%; p = 0.003).

Conclusion

Among the different anti-TNF treatment, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile. Current possibility of optimising also GOL will clarify whether these discrepancies are due to reduced drug exposure to GOL.
P669 Adherence to self-administered biologic therapies in inflammatory bowel disease: Experience in a tertiary hospital
Authors: Ramos Lopez L , Ramos Rodríguez J , De La Barreda R , Guitierrez F , Nazco Casariego G J , Alonso Abreu I , Carrillo Palau M , Quintero E
Published: January 2020

Background

Nonadherence to medications is common in patients with inflammatory bowel disease (IBD) and can result in disease complications, therapy escalation, and the need for corticosteroids. The aim of this study was to assess adherence to self-administered (subcutaneous) biologic medications prescribed for IBD and to identify risk factors for biologic nonadherence.

Methods

A retrospective cohort study was performed on IBD patients starting and receiving subcutaneous biologic therapies from January 2016 to July 2019. Medical records were retrospectively reviewed and demographic and IBD data were collected. A modified medication possession ratio (mMPR) was calculated for the first 12-month treatment and at the end of follow-up (global-42 months). Nonadherence was defined as mMPR of less than 90%. Multiple regression analysis was performed to assess risk factors associated with non-adherence therapy

Results

A total of 154 patients (84M/70F; mean age starting biologic treatment 36 ±14 years; Crohn’s disease n = 118/ ulcerative colitis n = 31/ indeterminate colitis n = 5) were included; 121 received Adalimumab (ADA) and 33 were on Ustekinumab (UST); 63% of patients were naive to anti-TNF and 16.9% had received >2 previous biological treatment. Mean time from IBD diagnosis to use of subcutaneous biological agent was 16 ± 10 months. Mean time of subcutaneous agents use was 17.6(SD11.0) and 17.08 (SD6.8)months for ADA and UST, respectively. Global nonadherence (n = 154) (≤90% mMPR) was 6.6% for all patients receiving subcutaneous treatment and 6.3% for ADA and 6.5% for UST. Nonadherence during first 12-month treatment (n = 98) was 6.1% for all patients and 2.7 % for ADA and 16% for UST, respectively. In the multivariate analysis, Ustekinumab use was independently associated with higher nonadherence only for first 12-months adherence (OR 6.7, 95% CI 1.1–39.5).

Conclusion

Self-administered biologic treatment showed adequate global adherence in our study. Using subcutaneous administration for biologic agents in IBD patients forces us to monitor and control their adherence to ensure the therapeutic benefit.
P670 Usefulness of monitoring the concentration of azathioprine metabolites in the children with inflammatory bowel disease and autoimmune hepatitis
Authors: Bąk-Drabik K , Duda-Wrońska J , Dąbrowska-Piechota D , Adamczyk P
Published: January 2020

Background

Azathioprine (AZA) is an immunosuppressive drug, which is metabolised in the liver and kidneys into 6-thioguanine- the form responsible for the therapeutic effect. Despite its anti-inflammatory, antibacterial and immunomodulating properties, azathioprine has also dose-related side effects, such as bone marrow suppression, liver damage and pancreatitis. The purpose of this study was to assess the usefulness of monitoring the concentration of azathioprine metabolites: 6-tioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in the group of paediatric patients with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).

Methods

The clinical data of 46 paediatric patients (24 girls) with IBD and AIH, aged 8–17 years, hospitalised in the Department of Gastroenterology, who had undergone a blood examination for AZA metabolites concentration, were analysed.

Results

Initial mean dose of azathioprine was 1.23 mg/kg/day in IBD and 1.16 mg/kg/day in AIH. In 30% of patients, the concentrations of 6-TG and 6-MMP were within the normal range. Forty-eight per cent of patients required a dose change due to: elevated 6-TG concentration (32.6%) or underdosage (15.4%). After modification the mean dose was 1.16 mg/kg/day in IBD and 0.85 mg/kg/day in AIH. In 10.7 % of patients, the concentrations of 6-TG and 6 MMP were below the proper range, in the same percentage of patients metabolites were undetectable.

Conclusion

In a significant number of cases monitoring the concentration of AZA metabolites indicated the necessity to reduce the dose of AZA allowing to achieve the therapeutic optimum and prevent serious side effects. Receiving undetectable concentration of metabolites is a sign of non-compliance. The final doses of AZA were found to be lower than the recommended doses. Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels is a good strategy that can be used to optimise IBD and AIH therapeutics.
P673 Strategy of selecting anti-TNF agent in patients with Crohn’s disease: A multi-centre retrospective cohort study by the Osaka gut forum
Authors: Amano T , Shinzaki S , Tashiro T , Otake Y , Tani M , Yoshihara T , Iwatani S , Tsujii Y , Inoue T , Hayashi Y , Iijima H , Takehara T
Published: January 2020

Background

Previous reports showed that disease activity before treatment affected long-term continuation of anti-tumour necrosis factor (anti-TNF) therapy in patients with Crohn’s disease (CD). However, there is no consensus about which anti-TNF agent should be selected dependent on patient’s condition. The aim of this study was to investigate factors affecting the continuation period of anti-TNF therapy and to clarify how to select each anti-TNF agent in patients with CD.

Methods

This was a retrospective multicenter cohort study of consecutive patients who started anti-TNF therapy (infliximab: IFX or adalimumab: ADA) as an induction therapy from January 2010 to March 2019 at 16 hospitals participating in the Osaka Gut Forum. We excluded patients who did not respond to therapy or had toxic events within 8 weeks. Factors affecting the continuation period of each anti-TNF agent such as backgrounds, blood tests, clinical features before treatment and concomitant medications were analyzed by the Cox proportional hazards model. The cumulative continuation rate of each agent was analyzed by the Kaplan–Meier method and evaluated by log-rank test.

Results

A total of 250 patients were enrolled (IFX /ADA; 138 /148 treatments, bio-naïve; 73%, median age; 36 years [Interquartile range (IQR); 24–46], median disease duration; 2.0 years [0.0–11.0], median observation period; 4.5 years [3.9–5.0]). Median Harvey–Bradshaw Index (HBI), C-reactive protein (CRP) and Albumin (Alb) were 5 [3–8], 0.71 mg/dl [0.14–2.04] and 3.5 g/dl [3.0–4.0], respectively. In patients with Alb ≥3.5 g/dl before treatment (median value), patients treated with IFX showed no significantly higher continuation rate than those with ADA. However, in those with Alb <3.5 g/dl, patients treated with IFX (N =82) showed significantly higher continuation rate than those with ADA (N = 50) (p = 0.007). In the observation period, 50%/34% of patients treated with IFX /ADA increased dose and 29% /38% of them concomitantly used azathioprine. In patients with Alb <3.5g/dl, by univariate analysis, stricturing and penetrating disease (B2 and B3/B1) [hazard ratio (HR); 4.18, 95% Confidence interval (CI); 1.83–12.0], disease duration [HR; 3.57, 95% CI; 1.16–9.77], and IFX/ADA [HR; 0.48, 95% CI; 0.28–0.83] were extracted as factors affecting continuation period of anti-TNF therapy. Furthermore, B2 and B3/B1 [HR; 3.80, 95% CI; 1.60–11.2] and IFX /ADA [HR; 0.49, 95% CI; 0.26–0.92] were extracted by multivariate analysis. After 8 weeks after treatment, the increase in Alb level was significantly higher in patients with IFX than those with ADA (p = 0.006), although there was no difference in HBI and CRP.

Conclusion

When serum Alb level is less than 3.5 g/dl before treatment, IFX can be used longer than ADA for CD patients.
P682 Faecal calprotectin and C-reactive protein levels are associated with long-term clinical and endoscopic outcomes: Analysis of the OASIS open-label extension trial of etrasimod for ulcerative colitis
Authors: Yarur A , Chiorean M , Zhang J , Reinisch W , Vermeire S , Panés J , Peyrin-Biroulet L , Sands B E , Cabell C H , Naik S U , Sandborn W J
Published: January 2020

Background

Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE.

Methods

In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient.

Results

The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1.

Conclusion

FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.
P694 Validation of two commercial assays for therapeutic drug monitoring of adalimumab biosimilars
Authors: Berghmans R , Naudts J , Ferkinghoff B , Gören H , Henke M L , Lennerz A , Van Stappen T
Published: January 2020

Background

Therapeutic drug monitoring of adalimumab (ADM) is increasingly used to optimise the management of patients with inflammatory bowel disease. The recent settlements with Abbvie concerning Humira®, paved the way for biosimilar drugs to enter the European market. In this study, we aimed to validate two commercial assays, the RIDASCREEN® ADM Monitoring (ELISA; also known as the apDia Adalimumab ELISA) and the RIDA®QUICK ADM Monitoring (rapid assay), which were developed and validated using the originator drug, for the quantification of two ADM biosimilars, AMGEVITA® and Imraldi®.

Methods

To validate the RIDASCREEN® ADM Monitoring, accuracy and recovery were determined by diluting AMGEVITA® and Imraldi® to varying concentrations within the clinical measuring range and in comparison with Humira®. The specification of accuracy is met when the deviation of the measured ADM biosimilar value is within ±15% of the theoretical value. For the recovery, the deviation of the measured ADM biosimilar value has to be within ± 15% of the Humira® value. To validate the RIDA®QUICK ADM Monitoring for the quantification of AMGEVITA® and Imraldi®, the recovery and linearity was determined. The recovery was determined by spiking three samples containing a low concentration of ADM biosimilar with varying concentrations of ADM biosimilar. The rapid assay complies with the requirements of recovery, if the observed value of ADM biosimilar is within ± 20% of the expected value of ADM biosimilar. The linearity was performed on the basis of NCCLS-guideline EP6-A; a sample with high concentration of ADM biosimilar was diluted 1:1 to 1:38.4. All samples were measured in the ELISA and rapid assay following manufacturer’s instructions.

Results

In the RIDASCREEN® ADM Monitoring, the mean deviation of the measured AMGEVITA® and Imraldi® value vs. the theoretical value was −6.6% and 2.1%, respectively. Recovery of spiked AMGEVITA® and Imraldi® samples in serum revealed a maximum absolute deviation of 12.9% and 14.8% vs. Humira®. In the RIDA®QUICK ADM Monitoring, the mean recovery of three serum samples spiked with varying concentration of AMGEVITA® and Imraldi® ranged from 91% to 115%, and 95% to 101%, respectively. Linearity was shown for both AMGEVITA® and Imraldi®.

Conclusion

We successfully validated the biosimilars AMGEVITA® and Imraldi® in the RIDASCREEN® ADM Monitoring and RIDA®QUICK ADM Monitoring. These results encourage therapeutic drug monitoring of ADM biosimilars in routine clinical practice.
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

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