bluuebunny/crossref_metadata_2025 huggingface dataset:
P553 Safety of the sequential use of biological therapy in inflammatory bowel disease: Results from a tertiary referral centre
Authors: Moens A , Ballet V , Sabino J , Vermeire S , Ferrante M
Published: January 2020

Background

Switching between biological therapies is frequently observed in the routine management of inflammatory bowel disease (IBD). Yet, it is unknown whether sequential use of biologicals affects safety such as serious infections and malignancies. We aimed to compare the occurrence of serious infections and malignancies in regards to the number and classes of biologicals to which patients were exposed.

Methods

This retrospective cohort study included all IBD patients exposed to commercially available biologicals from 1999 to 2019 in a tertiary referral centre. Follow-up started at initiation of first biological. Exclusion criteria included: patients <18 years, episodic administration of biologicals or administration for another indication than IBD and loss to follow-up <2 years after initiation of first biological. Via review of full electronic medical records, we studied the development of serious infections (defined as any infection leading to hospitalisation or treatment change) and malignancies. Poisson and Cox regression models were used.

Results

In total 1374 patients were included (Figure 1). During a median (IQR) follow-up of 8 (4–13) years, 373 serious infections and 127 malignancies were reported in 245 (19%) and 92 (7%) patients, leading to an incidence rate of 2.2 and 0.8 per 100.000 patients per year, respectively. The number of serious infections was dependent on prior exposure to immunomodulators (IM, p = 0.001), the number of biologicals (p = 0.042) and the number of biological classes to which the patient was exposed (p = 0.004, overall test Poisson model p = 0.0001). The risk of serious infections increased when a patient was exposed to three or more different biologicals or two or more different classes of biologicals. The number of malignancies was also affected by the number of biologicals (p = 0.028) to which the patient was exposed, with a higher risk of developing a malignancy with exposure to an increasing number of biologicals (Figure 2 and 3). Cox regression for the time to develop a first or second malignancy was independent of exposure to IM, number of biologicals as well as number of different biological classes to which the patient was exposed. Median (IQR) time to develop a first or second malignancy after the start of the first biological was 6 (3–9) and 6 (4–12) years.

Conclusion

In this large single-centre cohort study spanning 20 years, the overall risk of serious infections and malignancies in patients exposed to biologicals remains low, yet the risk increased with more and sequential use of biologicals so close vigilance is needed.
P561 The management of Crohn’s disease (CD) patients post ileocaecal resection: a multicentre, regional audit in Northern England
Authors: BATCHELOR S , Speight A
Published: January 2020

Background

70% of patients with Crohn’s disease (CD) require intestinal resection.1 Post-operative recurrence (POR) is common with 70% of patients requiring further surgery in the pre-biologic era.2 ECCO guidelines suggest identifying patients at risk of recurrence (disease phenotype, smoking, prior resection), the use of imidazole antibiotics following surgery and assessment for recurrence within 12 months. The ECCO guidelines recommend ileocolonoscopy, although alternative modalities can be used. The Rutgeerts score predicts POR and is recommended to establish the need for preventative treatment.3 The aim of this study was to undertake a region-wide audit of practice with regards to post-operative CD in the Northern region.

Methods

A regional, multicentre, retrospective audit was conducted by GRANT, a network of gastroenterology trainees in Northern England. Data collection was performed for CD patients who had an ileocaecal resection between 1/9/16 and 1/9/17. Patients with an end-ileostomy were excluded. Patients were identified using clinical coding and data collection sheets were completed.

Results

Seven of 9 Hospital Trusts returned data. The number of eligible patients was 38 with a mean age of 41 years. Seventy-six per cent (29/38) patients had at least one risk factor rendering them ‘high-risk’ for POR (Figure 1). Only 13% (5/38) of patients received imidazole antibiotics postoperatively and only 29% (11/38) had an ileocolonoscopy within 12 months. However, 32% (12/38) had an alternative assessment of POR, with calprotectin being the most popular. An escalation in treatment following assessment was required in 25% (9/38) of patients. Postoperatively, 40% (15/38) of patients had no maintenance therapy before POR assessment; 26% (10/38) continued on the same therapy as preoperatively and34% (13/38) had augmented pre-operative therapy.

Conclusion

The majority of patients in Northern England who have an ileocaecal resection for CD are high risk for recurrence and many patients are not being assessed. Endoscopic POR predates clinical POR [4] and, without monitoring, the opportunity to augment therapy and prevent clinical recurrence can be missed. In Northern England, less invasive disease monitoring is being used to assess for POR and this audit would suggest that these have a comparable rate of identifying a need to escalate maintenance therapy. A postoperative CD management bundle is being developed and will be implemented to assess whether this drives improvement.
P563 Shared decision-making in pregnancy in inflammatory bowel disease: Design of a pregnancy in IBD decision aid (PIDA)
Authors: Williams A J , Leung Y , O’Connor K , Huang V
Published: January 2020

Background

A lack of IBD-specific reproductive knowledge has been associated with increased ‘voluntary childlessness’.Furthermore, a lack of patient and clinician knowledge may contribute to inappropriate medication changes during or after pregnancy that may lead to a flare of disease. Evidence exists for the benefit of decision aids to support decision-making in pregnancy in general, as well as in multiple other chronic disease; however, such a resource for pregnancy in IBD has not been identified.

Methods

Using International Patient Decision Aids Standards, we have commenced design of our Pregnancy in IBD Decision Aid (PIDA). A steering committee consisting of Canadian and Australian Healthcare professionals with an interest in IBD management in pregnancy, in addition to a patient representative was established. Initial patient and clinician focus groups were conducted. Themes prospectively chosen for discussion included inheritance, fertility, nutrition, medications, mode of delivery, breastfeeding, infant infections and vaccinations. We designed an electronic PIDA draft that incorporates individualised information (for example, type of IBD, pre-conception or pregnant, surgical history and current medications) in personalised decision-making. Further patient focus groups and interviews were conducted to obtain user opinion of the PIDA draft.

Results

In July 2017, patient and clinician focus groups were conducted at a Canadian site. Patient concerns regarding pregnancy included the impact of disease, previous surgical history on fertility, preterm delivery; the potential impact of current and past drug therapies on the fetus/ infant; and the negative impact of active disease on both maternal and fetal/infant health. Clinician concerns included the absence of pre-conception counselling and potential for lack of patient understanding about the impact of disease activity and IBD medication use in pregnancy. Patient feedback (n = 15) obtained through interviews at two Canadian and one Australian site regarding the current electronic PIDA draft was predominantly positive, with comments pertaining to the adequacy of content coverage, personalisation, readability and unbiased information presentation. Suggestions were made for inclusion of further content such as the impact of IBD on sexual function, expected laboratory changes and the timing of recommencement of medications post-partum.

Conclusion

The completion of pre and post-PIDA design focus groups and interviews affirmed the role for PIDA. Main decisions that were considered necessary to address included ideal timing of conception pending disease activity, management of medications and delivery methods. Ongoing user feedback is being obtained at Australian and Canadian sites currently.
P564 Psychological acceptance of surgery in patients with inflammatory bowel disease undergoing intestinal resection
Authors: Hirano Y , Itabashi M , Saito T , Uchida K , Inoue M , Katsuhiro A , Atsuhiro H , Araki K , Nishikawa Y , Tatsuno M , Hideaki K , Reiko K
Published: January 2020

Background

To decision to undergo surgical intestinal resection is among the most difficult that patients with inflammatory bowel disease (IBD) may be required to make during the disease course. Although the clinical outcomes and QoL after intestinal resection are well established, few studies have focused on psychological acceptance of the surgery, that is, how patients feel about the results of intestinal resection. The aim of this study was therefore to evaluate psychological acceptance of the surgical outcome in patients undergoing intestinal resection.

Methods

We administered a cross-sectional questionnaire survey to patients at five IBD centres in Japan who had undergone intestinal resection at least 1 month before the survey. Patients were asked to complete a visual analogue scale (VAS) questionnaire, consisting of 20 questions related to surgical acceptance and concerns related to IBD (body image, burden of treatment, interpersonal relationships), before and after surgery. The VAS scores before surgery were described by the patient looking back on recollection. Pre- and post-surgical VAS scores were compared using a Wilcoxon’s rank-sum test.

Results

A total of 64 patients participated in this study (median age at surgery 37.9 (range 12–67) years, median years after surgery 5.0 (range 0.1–21) years). The VAS scores before and after surgery were summarised in the figure. The score for ‘pleased to have surgical resection of my intestine’ improved significantly after the surgery in both UC and CD (p < .0001).Furthermore, the score for ‘burdened with treatment for my IBD’ improved significantly after surgery in UC patients (p < .0001).

Conclusion

Our findings indicate that surgical intestinal resection outcomes were psychologically well accepted by most IBD patients.
P573 Frequency and effectiveness of empirical anti-TNF dose intensification in inflammatory bowel disease: an on-going systematic review with meta-analysis
Authors: Guberna Blanco L , Nyssen O P , Chaparro M , Gisbert J P
Published: January 2020

Background

Loss of response to anti-TNF therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remain unclear. Our aims were: (1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; (2) To evaluate possible variables influencing its requirement; (3) To assess the effectiveness of empirical DI.

Methods

Bibliographical searches were performed until January 2019. Selection: prospective and retrospective studies assessing the loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: Studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data were analyzed by means of the inverse variance method using a random effect model and stratifying by medical baseline condition (UC vs. CD), anti-TNF drug and follow-up. Effectiveness was assessed by intention-to-treat analysis.

Results

Up to now, 107 studies (11,377 patients) were included. The overall rate of DI requirement for naïve patients after 12 and 36 months of follow-up was 35% (95% CI=26–45%, I2=95%, 15 studies) and 48% (41–55%, I2= 77%, 9 studies); respectively. Frequencies of DI requirement stratified by subgroup analysis are presented in the table (all patients being naïve except CD patients treated with adalimumab (ADA), including naïve and no naïve).

The overall short-term response and remission rates to empirical DI were 67% (95% CI: 63–72%; I2=73%; 31 studies) and 45% (95% CI: 35–55%; I2=9%; 23 studies), respectively; subgroup analyses are summarised in the table.

Conclusion

Loss of response to anti-TNF agents and consequent DI occurs frequently in both UC and CD, with an overall rate of DI requirement of 35% at one year and 48% at 3 years. Empirical DI is a relatively effective therapeutic option. Further data extraction and analysis is necessary to confirm these findings.
P575 Real-world effectiveness and safety of ustekinumab for the treatment of refractory Crohn’s disease: The Scottish ustekinumab cohort
Authors: PLEVRIS N , Robertson A , Fulforth J , Hall R , Campbell I , Kane C , Veryan J , Lam W , Saunders J , Jenkinson P , Chuah C , Kelly C , Watts D , Gaya D , Macdonald J , Jafferbhoy H , Seenan J P , Mowat C , Sutherland D , Naismith G , Bain G , Arnott I , Jones G , Lees C
Published: January 2020

Background

Ustekinumab (UST) is an anti-IL12/23 biologic licensed for the treatment of moderate to severe Crohn’s disease (CD). The aims of this study were to establish the long-term real-world effectiveness and safety of UST for the treatment of CD in a large UK cohort.

Methods

This was a multicentre retrospective cohort study , including 7 NHS health-boards in Scotland. Patients treated with UST between November 2015 and June 2019 were identified. Inclusion criteria included: a diagnosis of CD; active symptoms attributed to CD with objective evidence of mucosal inflammation (CRP >5mg/l or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/ MRI); and completion of induction with a minimum of 8 weeks follow-up. Clinical assessments were performed based on physician global assessment (response was defined as ≥50% reduction in CD-related symptoms and remission defined as complete resolution of all CD-related symptoms). Mucosal healing was defined as the absence of ulceration/erosions on ileo-colonoscopy or no inflammation on MRI if ileo-colonoscopy was not possible (eg. B2 disease). Deep remission was defined as clinical remission plus mucosal healing. Rates of serious adverse events (discontinuation of UST, hospitalisation or death) during follow-up were described quantitively.

Results

A total of 207 patients (43% male; median age 39.2 years, IQR 28.9–51.4; median disease duration 10.0 years, IQR 5.7–16.6) with a median follow-up of 34.6 weeks (IQR 16.9–52.1) were included. The majority of patients had ileocolonic disease (L1, 19.3%; L2, 23.7%; L3, 57%) and an inflammatory phenotype (B1, 43.0%; B2, 41.1%; B3, 15.9%). A total of 98.6% of patients had previously been exposed to a biologic and 55.1 % had undergone previous surgery. Seventy-one per cent of patients received Q8 maintenance dosing, whilst 25.6% and 42.0% of patients were also receiving an immunomodulator (IMM) and steroids at initiation, respectively. At week 8, clinical response and remission rates were 51.7% and 5.8%, respectively. Twelve-month cumulative rates of clinical remission, mucosal healing (n = 116) and deep remission (n = 116) were 29.8%, 35.3% and 17.9%, respectively (Figure 1). During 155 patient-years of follow-up (PYF), 11 patients experienced a serious adverse event (7.1 per 100 PYF).

Conclusion

We have shown in a large real-world cohort of complex, treatment-refractory CD patients that UST is a safe and effective treatment option.
P576 The value of small bowel capsule endoscopy in the change of therapeutic management in patients with established Crohn’s disease
Authors: Viazis N , Tsoukali E , Pontas C , Karampekos G , Gkeros F , Filippidis G , Vraka M , Koustenis K , Mountaki K , Mitselos I , Mela M , Christidou A , Archavlis E , Vienna E , Christodoulou D , Mantzaris G
Published: January 2020

Background

Small bowel capsule endoscopy (SBCE) is widely used for various indications in patients with established Crohn’s disease (CD). Our aim was to investigate whether SBCE can lead to changes in the therapeutic management of CD patients.

Methods

Retrospective analysis of prospectively collected data [September 2003 - September 2019] from patients with established CD subjected to SBCE in two tertiary referral centres for inflammatory bowel diseases. All patients were tested with the Pillcam SB. Findings consistent with small bowel CD involvement were the presence of aphthoid or larger ulcers with or without inflammation of the adjacent mucosa.

Results

In total, 839 patients [median age (range) 36 (17–78) years, 471 (56.41%) men, median disease duration 6 years] diagnosed with CD according to established criteria underwent SBCE in the participating centres for the evaluation of disease extent and mucosal healing or the investigation of clinical relapse or iron deficiency anaemia. Based on ileo-colonoscopy findings disease location was documented in 618 patients (73.65%) as follows: colitis in 219 (26.10%), ileo-colitis in 253 (30.15%), and terminal ileitis in 146 (17.40%) patients; in contrast, full disease location was not documented in 221/839 (26.34%) patients who had colonic involvement but the ileocaecal valve could not be intubated. In the latter group, SBCE revealed small bowel involvement in 96 (43.43%) patients. In addition, SBCE revealed more proximal lesions in 105/618 (16.99%) patients with ileo-colonoscopy documented colitis, ileo-colitis or terminal ileitis. These findings led to a change in therapeutic management in 98 patients (11.68%): 36 patients (4.29%) received biologics, 21 patients (2.50%) received intensified doses of or changed the administered biologic, 39 patients (4.64%) received corticosteroids and/or conventional immunosuppressants and 2 patients (0.23%) underwent surgery. Therapeutic management changes were commoner in patients in whom small bowel lesions were found during SBCE and in whom the terminal ileum had not been examined during colonoscopy (57/96 patients vs. 41/105, p = 0.003]. Capsule retention occurred in 9 patients (1.07%) and passed after administration of corticosteroids (n = 6), or the capsule was retrieved with push enteroscopy (n = 1) or surgery (n = 1).

Conclusion

SBCE is a valuable tool in the management of patients with established CD, especially in those whom the terminal ileum has not been examined during the preceding colonoscopy.
P582 Adalimumab therapeutic drug monitoring: Does time of testing matter?
Authors: Shields S , Seenan J P , Dunlop A , Galloway P , Macdonald J
Published: January 2020

Background

Whilst anti-TNF drugs such as adalimumab (ADL) have revolutionised the management of inflammatory bowel disease treatment outcomes are not universally favourable with 30% primary non-response (PNR) and 46% secondary loss of response (SLOR) rates reported.1,2 Therapeutic drug monitoring (TDM)—the measurement of serum drug levels and anti-drug antibodies—has become popular with clinicians who use it to optimise biologic therapy through serum drug-level guided dose adjustment. Conventionally TDM is based on the interpretation of trough drug levels (DL) which are obtained by drawing a blood sample immediately prior to the next drug dose. Obtaining an ADL trough DL can be challenging as the drug is administered as a subcutaneous injection usually in the patient’s own home. The aim of this project was to determine the current use of non-trough ADL TDM in clinical practice and determine whether timing of ADL TDM in relation to the next planned dose is clinically important.

Methods

All ADL DLs performed in 2018 in the Scottish Biologic TDM service3 were identified. DLs were included for patients in sustained clinical remission (SCR), on 40mg every other week dosing, and if the time from the last dose was ≤14 days. TDM performed during induction and for PNR or SLOR were excluded, as were patients on nonstandard dosing or with missing data on dose and interval. Results were analysed by quartile according to time from the last drug dose.

Results

338 DLs were included. Median DL is 8µg/ml (range <0.4–36). Median time from last dose is 12 (range 0–14) days. The first quartile (n = 83, median 5 (range 0–7) days) had a median DL of 8.2µg/ml (<0.4–28.1). The second quartile (n = 90, median 11 (8–12) days) had a median DL of 7.9µg/ml (<0.4–36). The third quartile (n = 80, 13 days from last dose) had a median DL of 8µg/ml (<0.4 – 28.1). fourth quartile samples (n = 85, 14 days from last dose – true trough DLs) had a median DL of 8 µg/ml (<0.4–34.8). No relationship was identified between observed DL and the time of DL testing (ρ= -0.3162, p = 0.23).

Conclusion

It is not necessary to use trough DLs when performing ADL TDM for individuals in SCR. These data should give clinicians the confidence to use opportunistic ADL TDM testing in a clinical setting. Further work should be undertaken on non-trough testing of ADL DLs in other clinical scenarios.

Disclosure

Biogen GmbH contributed funding for this research. Authors had full editorial control and approval of all content.

References
P585 Evaluation and comparison of the safety profiles of different intravenous iron preparations and oral iron for treatment of iron deficiency anaemia: Preliminary results from the IBD subgroup analysis
Authors: Aksan A , Işık H , Aksan S , Tuğal D , Dignass A , Stein J M
Published: January 2020

Background

Current ECCO guidelines state that intravenous (IV) iron should be considered first-line treatment in patients with clinically active IBD, previous intolerance to oral iron, Hb below 100 g/l and patients who need erythropoiesis-stimulating agents. Several different IV iron products are available with differing therapeutic effectiveness and tolerability. In this ongoing study, we compare their safety profiles to establish whether any IV iron carries an increased risk compared with other IV iron products or with oral iron, and to determine which, if any, has a superior safety profile. We report preliminary results from an IBD subgroup analysis.

Methods

We performed a systematic review and network meta-analysis (NMA), searching PUBMED, SCOPUS, WoS and Cochrane Library up to July 2019. The primary outcome measure was the pooled total of drug-related adverse events (AEs) and serious AEs (SAEs) in proportion to the safety population. The secondary outcome measure was identification of the most common AEs.

Results

8086 distinct publications were found. Of 171 relevant full-text articles on IBD, 5 RCTs (n = 1143) were eligible. Bayesian NMA was performed using a fixed effects model. Low statistical heterogeneity was determined (I2= 9%). AE rates did not differ significantly between the different IV iron products (ferric carboxymaltose/FCM; iron sucrose/IS; iron isomaltoside/IIM) or oral iron. Compared with oral iron; OR=0.69, 95% CrI [0.29;1.7] for FCM, OR=0.52, 95% CrI [0.22;1.2] for IS, OR=1.5, 95%CrI [0.80;3.1] for IIM. Compared with FCM; OR=0.74, 95% CrI [0.45;1.2] for IS, OR=2.2, 95% CrI [0.74;6.7] for IIM. Compared with IS; OR=0.1.3, 95% CrI [0.82;2.2] for IS, OR=3.0, 95% CrI [1.0;9.1] for ISM. Compared with IIM; OR=0.45, 95% CrI [0.15;1.3] for FCM, OR=0.33, 95% CrI [0.11;1.0] for IS. The most common AEs were headache (1.8%) and transient hyperferritinaemia (1.8%) for FCM; headache (1.5%), hyperferritinaemia and rigors (both 1.2%) for IS; flushing (2.7%), hypersensitivity and hepatic enzyme increase (both 1.8%) for IIM; diarrhoea (8.0%) and abdominal pain (7.7%) for oral iron. Hypophosphataemia was reported in only 1 RCT of FCM, here transient and clinically asymptomatic. Seven SAEs were recorded; 1/381 for FCM, 1/223 for IIM and 5/238 for oral iron.

Conclusion

None of the IV iron products was associated with an increased risk of AEs or SAEs compared with oral iron and all showed similarly low rates of AEs. However, their safety profiles differed: Whereas with FCM or IS, headaches were most commonly reported, IIM was more frequently associated with hypersensitivity reactions or increase in hepatic enzymes. On this evidence, while FCM, IS and IIM are all safe, their differing safety characteristics should be considered in therapeutic decision-making.
P586 Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease
Authors: GU B , Venkatesh K , Williams A J , Ng W , Corte C , Ghaly S , Xuan W , Paramsothy S , Connor S
Published: January 2020

Background

Anti-TNF α agents, including infliximab (IFX) and adalimumab (ADA), are arguably the most effective medical therapies for fistulising perianal Crohn’s disease (CD). Increased rates of perianal fistula healing have been reported with increased IFX trough levels. Our study aimed to determine the correlation between perianal fistula healing and closure with IFX and ADA trough levels in fistulising perianal CD patients on maintenance therapy.

Methods

In this multi-centre retrospective cross-sectional study, we identified CD patients with perianal fistulae on maintenance IFX or ADA who had an IFX or ADA trough level within 3 months of clinical assessment. Data collected included demographics, serum IFX and ADA trough levels (mg/l) and concomitant medical and surgical therapy. The primary outcome was fistula healing, defined as a cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing as well as closure of all external fistula openings. Receiver operating characteristic (ROC) curve analysis was performed to identify the IFX and ADA concentration cut-off points with combined maximal sensitivity and specificity that corresponded to fistula healing.

Results

A total of 123 patients (IFX = 72; ADA = 51) were included. Fifty-four (75.0%) patients on maintenance IFX achieved fistula healing and 22 (30.6%) achieved fistula closure. Patients who achieved fistula healing had significantly higher median IFX trough levels compared with patients who did not [6.2 (interquartile range 3.1 - 9.6) vs. 3.0 (0.3 - 6.2), (p = 0.007)]. The median IFX trough levels for patients with and without fistula closure were not significantly different [6.4 (2.9 - 9.8) vs. 4.9 (2.5 - 8.9), (p = 0.277)]. Forty (78.4%) patients on maintenance ADA achieved fistula healing and eighteen (35.3%) fistula closure. Patients who achieved fistula healing had a significantly higher median ADA level compared with those who did not [8.7 (6.6 - 12.0) vs. 5.4 (2.5 - 8.3), p = 0.007]. The median ADA trough levels for patients with fistula closure and without fistula closure were not significantly different [9.6 (6.7 – 12.0) vs. 7.7 (4.4–9.8), p = 0.098]. An IFX cut off point of 6.10mg/l was associated with healing (sensitivity 52%; specificity 78%; area under the curve (AUC) 0.72). An ADA cut off point of 7.05mg/l was associated with healing (sensitivity 70%; specificity 73%; AUC 0.77).

Conclusion

Higher IFX and ADA trough levels are associated with fistula healing. No association between IFX and ADA trough levels and fistula closure was seen, although larger numbers may be required. To the best our knowledge, this is the first study to demonstrate a significant association with both higher IFX and ADA levels with fistula healing in perianal CD.
P588 vedolizumab trough levels at week 6 and 14 correlate with clinical remission in inflammatory bowel disease patients
Authors: Marino M , Domenis R , Biribin L , Cifù A , Navarria L , Scardino G , Fabris M
Published: January 2020

Background

Vedolizumab (VDZ) is a therapeutic monoclonal antibody against α 4β 7 integrin approved for the treatment of inflammatory bowel diseases (IBDs). A relationship between VDZ exposure and clinical efficacy has been highlighted by several studies, but data are still controversial. In this perspective, our study aims to investigate the clinical usefulness of VDZ drug monitoring during the induction phase to support therapeutic management of IBD patients in the real life.

Methods

This retrospective study focus on a single cohort of 25 IBD patients (7 with Crohn’s disease and 18 with ulcerative colitis) treated with VDZ between 2016 and 2019. VDZ trough levels (TLs) and anti-VDZ antibodies (AVA) were measured before infusion at weeks 6, 14 and 22, using Promonitor® ELISA assays (Grifols). Disease activity was evaluated using international criteria, defining clinical remission when Mayo Partial Score <2 and Harvey–Bradshaw Index <5.

Results

VDZ TLs showed a significant inverse correlation with disease activity at each time point (week 6: Spearman’s rho = −0.659, p = 0.0003), (week 14: Spearman’s rho = −0.634, p = 0.0009), (week 22: Spearman’s rho = −0.476, p = 0.029). The median VDZ TLs was significantly higher in patients in clinical remission when compared with those with active disease, either at week 6 (42.3 vs. 19.8 µg/ml, p = 0.0005), and at week 14 (23 vs. 8.6 µg/ml, p = 0.003). Of note, at week 6, patients with VDZ TLs >24 µg/ml were significantly associated with a state of clinical remission compared with those showing VDZ TLs <24 µg/ml (9/12, 75% vs. 1/13, 7.7%; OR=36, [95% CI=3.19–401], p = 0.001). Anti-VDZ antibodies were detected in 1 patient out of 25 (4%).

Conclusion

VDZ TLs in the induction phase correlate with the clinical score in IBD patients, helping the management of the therapeutic efficacy of VDZ, from the very beginning of the biological treatment. In particular, at week 6, VDZ trough levels > 24 µg/ml may represent a potential drug concentration target to achieve long-term remission.
P589 Longer-term outcomes in patients with Crohn’s disease who are primary non-responders to anti-TNF in a single UK centre
Authors: HODGES P , Saunders J , Betteridge F
Published: January 2020

Background

Primary non-response (PNR) is reported to occur in up to 24% patients with inflammatory bowel disease treated with anti-TNF drugs. The longer-term outcomes of these patients are less well documented however it is recognised that this group represents a significant treatment challenge. We report retrospective outcomes for these patients from a single centre.

Methods

All patients with Crohn’s disease who stopped anti-TNF therapy because of PNR from 2013 to 2017 were identified from our database. Data were retrospectively collected from electronic patient records.

Results

124 patients were started on anti-TNF therapy in this 4-year period and PNR occurred in 26 of these (21%). Median follow-up was 43.5 months.

Following PNR 9 (34.6%) patients had surgery as next treatment although in the majority of these cases (6/9) this was before alternative class biologic drugs were available. 7 (26.9%) switched to an alternative anti-TNF again with the majority of these (5/7) being prior to the availability of other biologic class drugs. The subsequent outcomes for these patients are; 3 remain in remission, 1 failed to respond to an alternative anti-TNF and went on to have surgery within 1 year, 1 was in remission for 2 years then switched to vedolizumab, 2 were lost to follow-up or died for unrelated reasons. 6 (23.1%) switched to a different biologic class. Of these, 4 remain in remission, 1 required subtotal colectomy within 3 years, and 1 had 3 further biologic agents all of which failed and is now awaiting a trial drug or surgery. 2 (7.7%) switched to other immunomodulators. Two (7.7%) were lost to follow-up.

Conclusion

Overall 11 of the 26 (42%) patients required surgery within 3 years of primary anti-TNF failure. These data span a period during which vedolizumab and ustekinumab became available; therefore, the proportion of patients requiring surgery as next intervention is likely to be less now that these alternative drugs are available. In this cohort 4/6 patients who received alternative biologic class drugs who would previously have gone on to have surgery as the next intervention remains in remission (median follow-up 37 months). Although this is a small cohort, PNR response is shown to be a marker of poor prognosis with the availability of alternative biologics appearing to reduce the short-and medium-term need for surgery.
P590 Outcomes of patients treated with sequential anti-TNF therapy in a tertiary referral centre
Authors: Rowan C , O’Donnell J , Cullen N , O’Toole A , Boland K
Published: January 2020

Background

Anti-TNF agents are administered intravenously(iv) or subcutaneously(SC).Factors such as speed of onset and patient preference influence that decision. The aim of this study was to assess the characteristics and outcomes of patients transitioned between iv and sc anti-TNF therapy.

Methods

Patients attending a single tertiary referral centre, treated with two different anti-TNF drugs were included. Patient and disease characteristics, biochemical, endoscopic and radiological data were collated.

Results

69 patients were included. Table 1 describes the patient cohort. 28 (40.6%) patients transitioned from SC anti-TNF to infliximab (IFX). N=35 (50.7%) switched from IFX to Adalimumab and 6 to Golimumab. 31 patients demonstrated some degree of endoscopic activity prior to anti-TNF switch;14/16 (87.5%) demonstrated radiological activity. 48 patients had endoscopic assessment post-switch; 28 (58.3%) had endoscopic remission.Of the 19 patients with post-transition imaging, 42.1% (8/19) had no active disease. 43 (79.6%) patients had therapeutic trough concentrations of the current anti-TNF. 13 (26%) were previously on combination therapy, while 22 (32.8%) currently are. 24 (39.3%) patients had detectable anti-drug antibodies to their prior anti-TNF, 10 (16.4%) had primary non-response and 12 (19.7%) had loss of response with adequate drug levels. There were significantly more patients with antibody formation in the group switching from IFX to SC anti-TNF (n = 20; p = 0.001). A significantly higher proportion of patients who were transitioned from IFX to SC anti-TNF currently have therapeutic/supratherapeutic drug levels when compared with patients transitioning SC to IFX (p = 0.01). There is no significant difference in the proportion currently on combination therapy (p = 0.668). There is a significant improvement in c-reactive protein, albumin and haemoglobin in the cohort as a whole. However, there is no significant difference in rates of clinical remission (p = 0.556) or endoscopic remission (p = 0.89) after switching from one mode of delivery to another.

Conclusion

Patients converted from IFX to SC anti-TNF have similar rates of endoscopic and clinical remission to those transitioned to IFX. However, many patients had previous antibody formation. Subsequently, this group has significantly higher rates of therapeutic or supra-therapeutic drug concentrations, suggesting the conscientious use of therapeutic drug monitoring to optimise response.
P593 Predictors of steroid-resistance in severe colitis of inflammatory bowel disease
Authors: JEMMALI C , Labidi A , Jouini M A , Hafi M , Serghini M , Fekih M , Boubaker J
Published: January 2020

Background

Intravenous steroids (IVS) remain the mainstay of therapy in severe colitis of inflammatory bowel disease (IBD), although 30 to 40% of patients will not respond. In such cases, rescue medical therapy with immunomodulators, or an early colectomy are considered. The aim of this study was to identify predictor factors of corticosteroid failure during severe colitis in IBD patients.

Methods

We conducted a 5-year retrospective study (2014–2019), including all IBD patients with severe colitis. Diagnosis was based on clinical, biochemical markers and endoscopic criteria. All patients received conventional first-line therapy with IVS. Corticosteroid failure was defined according to Travis criteria.

Results

A total of 40 patients with a mean age of 36 ± 13.1 years and a sex ratio H / F of 0.6 were included. Twenty-three patients (57.5%) had ulcerative colitis (UC) while 17 patients (42.5%) had Crohn’s disease (CD). The average duration of IBD in all patients was 28.8 ± 52.1 months. Severe colitis was the first flare of the disease in fifteen patients (37.5%). Twenty-seven patients (67.5%) respond to IVS. Factors associated with steroid failure on admission were type of IBD (UC) (p = 0.03), presence of fever (T≥ 38°C) (p = 0.04) and blood transfusion (p = 0.02). Biochemical predictors of steroid failure were low hematocrit rate (<28%) (p = 0.03) and hypokalemia (K+<3.5mmol/l) (p = 0.004). Upon 3 days of IVS, a reduction less than 40% in stool frequency, thrombocytosis (platelets> 474000/mm3) (p < 0.001), high-CRP level (> 43mg/dl) (p = 0.026) are predictors of steroid failure. Upon 5 days of IVS, high-CRP level (> 12,1mg/dl)(p = 0.021) was significantly associated with steroid failure.

Conclusion

In conclusion, stratification of risk in IBD patients with severe colitis should be considered early on admission and at the latest on day 3 of IVS in order to select patients at high risk of steroid failure and then decide to start rescue therapy.
P601 Development and validation of dried blood spot sampling as a tool to identify the best time point to measure predictive ustekinumab serum concentrations in patients with Crohn’s disease
Authors: Van den Berghe N , Verstockt B , Vandeput E , Ballet V , Gils A , Ferrante M , Vermeire S , Thomas D
Published: January 2020

Background

Therapeutic drug monitoring of ustekinumab (UST), a monoclonal antibody directed against the p40 subunit of IL12/23, can serve as a tool to identify underexposed Crohn’s disease (CD) patients, as UST concentrations have been linked to treatment response. Drug concentrations are most often measured when a patient is losing response. To reduce the risk of loss of response, drug concentrations could be measured upfront to predict the chance of achieving response later on and optimising treatment if necessary. Identification of the optimal time point to measure UST levels that have a predictive value for long-term outcome requires studies with multiple sampling. Dried blood spot (DBS) sampling allows convenient and remote collection of a blood drop through a small finger prick. The current study aimed to develop and validate the DBS method in order to identify the best time point to measure UST concentrations to predict long-term outcome in CD patients and explore the pharmacokinetic profile.

Methods

UST concentrations (0.2–80 μg/ml) were spiked in citrated whole blood and 40 μl was spotted onto protein saver cards. After punching a 6mm disc, DBS was extracted and the UST concentration was measured with an in-house developed MA-UST56A2D11/MA-UST56C1H12 ELISA. The extraction efficiency, accuracy, precision and the effect of anti-UST antibodies on UST detection were evaluated. Additionally, the effect of the spotted blood volume, the stability of the DBS card at room temperature (RT) and DBS extract at -20°C was examined. To evaluate the correlation between UST in DBS extracts and serum, DBS and serum were simultaneously collected from 8 UST-treated CD patients at two different time points.

Results

Spiking UST to citrated whole blood and subsequent spotting and extraction revealed an average extraction efficiency of 65 ± 9% (n = 11). The accuracy and imprecision of all concentrations tested were 92–109% and 11–18%, respectively. Addition of anti-UST antibodies to spiked UST samples caused a similar decrease in UST concentration in DBS extracts as in serum. Spotted blood volumes between 15 and 50 μl demonstrated similar recoveries. Storing the DBS card at RT for up to 2 weeks and DBS extract at -20°C for 2 months did not impair recovery. UST concentrations in DBS extracts (range: 0.55–12.1 μg/ml) from CD patients correlated strongly with those in serum (Pearson r = 0.982, p < 0.0001).

Conclusion

DBS is a robust method that facilitates multiple sampling for the determination of UST concentrations in CD patients. To explore the pharmacokinetic profile of UST and identify the best time point during induction to predict the long-term outcome, a prospective study in which multiple DBS are collected in active CD patients initiating UST is warranted.
P602 Changes in emotional health and work-related outcomes in patients with moderate to severe ulcerative colitis 1 year after diagnosis: Results from the MOSAIK cohort in Korea
Authors: PARK Y , Cheon J H , Park Y S , Huh K C , Shin J E , Cha J M , Kim Y S , Eun C S , Yoon S M , Park Y S , Ye B D , Seo B , Kim Y
Published: January 2020

Background

As the treatment paradigm of inflammatory bowel disease changes towards patient-centred treatment, it is becoming increasingly important to measure patient-reported outcomes (PROs). We aimed to identify the changes of emotional health and work- or activity-related outcomes one year after the diagnosis of ulcerative colitis (UC) and its predictors in patients enrolled in the moderate-to-severe UC in Korea (MOSAIK) cohort (ClinicalTrials.gov: NCT02229344).

Methods

The MOSAIK cohort is the first nationwide, prospective, inception cohort on moderate-to-severe UC in Korea. Between August 2014 and March 2017, consecutive patients from 30 tertiary hospitals were enrolled. PRO data including hospital anxiety and depression scale (HADS) for emotional health, and work productivity and activity impairment (WPAI) questionnaire for work- or activity-related outcomes, were collected within the first 4 weeks of diagnosis via patient surveys. Wilcoxon-signed rank tests and linear mixed-effects regression models were used for paired comparisons between baseline and 1 year and assessing the predictors of HADS and WPAI.

Results

Of the 368 enrolled patients, 333 eligible patients were analyzed. The mean age at diagnosis was 39 years and 57.7% (192/333) were male. A considerable number of patients had moderate to high (≥11 by HADS) levels of anxiety and depression (16.0% and 20.5%, respectively), and about half of patients had work and activity impairment (45.5% and 45.8%%, respectively) at baseline. After 1 year follow-up, significant reduction of anxiety and depression (mean difference [MD] in HADS score -1.3 for both anxiety and depression, P<0.001), as well as work and activity impairment (MD -24.1% and -22.4%, P<0.001) was noted. Higher disease activity (partial Mayo Score) during a one-year period was a significant predictor of anxiety, depression, work and social activity impairment. Among the symptoms of UC, abdominal pain was a significant predictor of depression and work and activity impairment, and weight loss and diarrhoea were significant predictors of activity impairment.

Conclusion

Newly diagnosed moderate-to-severe UC patients had considerable anxiety, depression, and work and activity impairment at baseline, but significant improvement was noted after 1 year. Controlling symptoms and disease activity was the most important factor to improve PROs after 1 year.
P603 Persistence of vedolizumab maintenance therapy: Findings from a Belgian registry
Authors: Louis E , Muls V , Bossuyt P , Colard A , Nakad A , Baert D , Mana F , Caenepeel P , Vanden Branden S , Vermeire S , D’Heygere F , Strubbe B , Cremer A , Coche J C , Setakhr V , Baert F , Vijverman A , Coenegrachts J L , Flamme F , Hantson A , Wijnen K , Piters E , Dolin P
Published: January 2020

Background

Clinical trials and observational studies have demonstrated the clinical efficacy of vedolizumab (VDZ) as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). This report presents long-term data on persistence of VDZ maintenance therapy in real-world clinical practice in Belgium.

Methods

The Belgian VDZ Registry (ENCePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres across Belgium. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months after enrolment with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as the Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2. Missing value imputation (last observation carried forward) was used to partially account for missing disease activity scores. If a 6-monthly disease activity score was missing, the disease activity score from the previous 6-monthly assessment was used.

Results

The mean duration of VDZ therapy, including use prior to enrolment, was 31 months, with 68% of CD patients and 75% of UC patients using VDZ therapy for 48 months. Clinical remission rate after 42 months of VDZ therapy was higher in UC (84%) than CD (67%), and higher for patients without prior anti-TNF therapy (87%) than those with prior anti-TNF therapy (70%).

Fifty-seven (29.4%) patients discontinued VDZ during follow-up, due to loss of response (n = 40), adverse event (n = 7), clinical remission (n = 4), pregnancy planning (n = 3), and patient choice (n = 3).

Conclusion

These real-world long-term Belgian data demonstrate a high persistence of VDZ maintenance therapy among both CD and UC patients, with highest clinical remission rates seen in patients with UC and those with no prior anti-TNF therapy.
P604 Can we reduce intravenous monoclonal antibody observation times without compromising patient safety? A single centre retrospective observational study
Authors: REES F , Packham A , Blake C , Hills E , Scutt G , St Clair-Jones A
Published: January 2020

Background

Monoclonal antibodies (MAbs) are integral to inflammatory bowel disease (IBD) management. The administration of intravenous (IV) MAbs, infliximab and vedolizumab, for Brighton and Sussex University Hospital patients is via an outpatient clinic. Licensing specifies lengthy observation times; infliximab for induction (infusion 1 to 3) and maintenance (infusion 4 onwards) requires 1 to 2 h observation. Vedolizumab for induction (infusion 1 to 2) requires 2 h observation and maintenance (infusion 3 onwards) 1-h observation. This can affect waiting times; 33% UK patients waited longer than two weeks for infliximab. A reduction in observation times could improve capacity but needs to be done without compromising patient safety.

Methods

A single centre observational study was conducted. Retrospective data were collected on all current patients receiving infliximab or vedolizumab at BSUH. Data were collected over 12 weeks (April to July 2019); patients seen twice in this period were included once. The presence of reaction from current and previous infusions was determined by patient questioning and patient records review. Reaction occurrence, nature and management were recorded.

There is not a grading system for IBD infusion-related reactions. To standardise we used the cancer Common Terminology Criteria for Adverse Events; grade 3 and above is designated severe (grade 5 being death).

Results

For infliximab 130 patients were reviewed with 2607 infusions administered in total. For vedolizumab 69 patients were reviewed with 557 infusions administered in total.

Due to the small sample size significance could not be reached.

The survival plot indicates high levels of ‘no reactions’ observed in the first 4 infusions of infliximab 97.7% (+1.6%, -4.7%), and first 3 infusions of vedolizumab 96.9% (+2.3%, −8.8%).

Considering capacity over 12 weeks, for infliximab a minimum of 121 could be recouped and 64 h for vedolizumab. Extrapolated this could equate to 740 h per year.

Conclusion

All reactions occurred within three infusions, were non-severe and managed within the infusion clinic. By removing the observation period from infusion 4 onwards, infusion clinic capacity could be increased but further data from multiple centres are required to prove significance.