bluuebunny/crossref_metadata_2025 huggingface dataset:
DOP35 Ambulatory care management of 70 patients with Acute Severe Ulcerative Colitis in comparison to 700 inpatients: Insights from a multicentre UK cohort study
Authors: Patel K V , Segal J , Sebastian S , Subramanian S , Conley T , Gonzalez H , Kent A , Saifuddin A , Hicks L , Mehta S , Bhala N , Brookes M , Lamb C , Kennedy N , Walker G
Published: May 2021

Background

Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Patients with ASUC can deteriorate rapidly and hence require close monitoring of vital signs correlated with clinical, biochemical and radiological investigations. Traditionally, patients are admitted to hospital to facilitate endoscopic assessment, exclude concomitant infective complications, monitor response to first-line corticosteroid treatment and determine the need for and timing of rescue therapy and/or colectomy. Ambulatory care pathways, which utilise outpatient monitoring and drug delivery, have been shown to deliver safe and effective treatment for conditions which have historically mandated hospitalisation e.g. pulmonary embolus. To date there are a paucity of data regarding the use of ambulatory pathways in ASUC cohorts. We used data from PROTECT, a UK multicentre observational COVID-19 i (IBD) study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.

Methods

Adults (≥ 18 years old) meeting Truelove and Witts criteria between 01/01/2019- 01/06/2019 and 01/03/2020–30/06/2020 were recruited to PROTECT (Figure 1). We utilised demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of rescue therapy and/or colectomy. Secondary outcomes included corticosteroid response, response to rescue therapy, colectomy, mortality and hospital readmission within 3-months. We compared outcomes in 3 cohorts: i) patients treated entirely in inpatient setting; ambulatory patients subdivided into ii) patients hospitalised and subsequently discharged to ambulatory care; iii) patients managed as ambulatory

from diagnosis .

Results

38%(23/60) participating hospitals used ambulatory pathways. Of 770 eligible patients, 700(91%) patients received entirely inpatient care, 55(7%) patients were discharged to ambulatory pathways and 15(2%) patients were managed as ambulatory from diagnosis. The rate of rescue therapy and/or colectomy (49%[339/696] vs 41%[22/54] vs 67%[10/15], respectively, p=0.18) (figure 2) and secondary outcomes were similar among all three cohorts. After 3-months follow up from the index ASUC diagnosis there was no significant difference in either rate of UC flare, readmission to hospital with UC flare or colectomy between the cohorts.

Conclusion

In the largest description of ambulatory ASUC care to date, we report an emerging practice which challenges treatment paradigms. Our data suggest ambulatory ASUC treatment may be safe and effective in selected patients but further studies exploring clinical and cost effectiveness as well as patient and physician acceptability are needed.
DOP39 Utilization and sustainability of biologics in UC - A nationwide study from the epi-IIRN
Authors: Atia O , Yogev D , Friss C , Focht G , Orlanski-Meyer E , Magen Rimon R , Ledderman N , Greenfeld S , Kariv R , Loewenberg Weisband Y , Gabay H , Nevo D , Matz E , Gorelik Y , Chowers Y , Dotan I , Turner D
Published: May 2021

Background

25% of UC patients fail to respond to induction therapy with biologics. In this nationwide study we aimed to evaluate trends in biologics utilization and sustainability in UC during the last 15 years.

Methods

This study was performed on data from four the four Israeli Health Maintenance Organizations, covering 98% of the population. Sustainability was defined as continuous treatment without IBD-related surgeries and at most one short steroid course. Sustainability was compared across different biologics utilizing a propensity score (PS) weighted analysis, estimated by generalized boosted modeling (GBM).

Results

13,231 patients were diagnosed with UC in Israel since 2005 (1,426 [11%] pediatric-onset,11,805 [89%] adult-onset), of whom 1,692 (13%) were ever treated with biologics (400 [24%] pediatric-onset, 1,292 adults [76%], OR 3.2 [95%CI 2.8–3.6]; p<0.001) with a median of 6.4 years follow up (IQR 3.4–9.9). Infliximab was the most common first-line treatment in both children and adults (75% and 54%, respectively, p<0.001). However, in recent years there was an increase in adalimumab and vedolizumab utilization in parallel with a decrease in infliximab (Figure). The rate of initiating biologics in the first year of diagnosis increased from from 11% during 2005–2010 to 25% during 2011–2014 and 61% since 2015 (p<0.001). The use of combination therapy with immunomodulators is becoming less common and decreased with infliximab: from 36% in 2010 to 17% in 2018 (p<0.001) and with adalimumab from 32% to 12%, respectively (p<0.001).

The sustainability rate in those treated with infliximab was 52% at one year from initiation of biologics, and 37% and 34% at three and five years, thereafter; compared to 55%, 43% and 40% with adalimumab and 72% and 67% after one and two years with vedolizumab. The primary non-response rate was 30% with infliximab, 31% with adalimumab and 16% with vedolizumab.

Sustainability was associated with earlier initiation of biologics during the disease course (HR 0.9 [95%CI 0.85–0.95]). In the PS-adjusted model where vedolizumab served as the reference, the sustainability of both infliximab (HR 0.7 [95%CI 0.6–0.95]) and adalimumab (HR 0.8 [95%CI 0.6–0.99]) were lower. Compared with monotherapy, combination therapy increased the sustainability rate with both adalimumab (HR 0.3 [95%CI 0.2–0.6]) and infliximab (HR 0.4 [95%CI 0.-0.6]), but not with vedolizumab (HR 1.4 [95%CI 0.98–2.1]).

Conclusion

Biologics are being increasingly used in UC but only half of patients sustain treatment at one year. Treatment is commenced earlier during the disease course, and this is associated with improved sustainability. Sustainability rate is higher with vedolizumab, and in combination therapy of IMM and infliximab or adalimumab.
DOP44 Long term outcomes of patients with untreated IBD - A population-based analysis from the epi-IIRN
Authors: Magen Rimon R , Atia O , Friss C , Ledderman N , Greenfeld S , Kariv R , Loewenberg Weisband Y , Gabay C , Shaoul R , Odes S , Matz E , Dotan I , Turner D
Published: May 2021

Background

Therapy in IBD is recommended in order to treat or prevent complications. In this nationwide study we aimed to assess the incidence of patients with IBD who were not receiving maintenance treatment after diagnosis and the duration of non-treatment.

Methods

This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all patients with IBD diagnosed from 2005 to 2019. Non-treatment was defined as lack of drug prescription of maintenance medication for at least six months from diagnosis. Sustainability was defined as lack of maintenance medications and without IBD-related surgeries. Cox regression model was used to explore estimated predictors of sustainability.

Results

A total of 30,168 patients were diagnosed with IBD in Israel since 2005 (16,936 [56%] Crohn’s disease [CD] and 13,231 [44%] ulcerative colitis [UC]). A total of 5,448 (32%) patients with CD were untreated, compared to 5,158 (39%) with UC (OR 1.35 [95%CI 1.3–1.4]; p<0.001). Non-treatment was more likely in adult compared to pediatric-onset (34% vs 21%, respectively, p<0.001 in CD; and 41%% vs 22%, respectively, in UC; p<0.001) (Figure 1). Sustainability rate in CD was 72%, 46%, 36% and 28% after one, two, five and ten years from diagnosis, while in UC the corresponding rates were 59%, 39%, 24% and 16%. In CD, sustainability was associated with older age at diagnosis (HR 0.996 [95%CI 0.994–0.998]) and no induction therapy (HR 0.7 [95%CI 0.6–0.9] compared to steroids). In UC, sustainability was associated only with female sex (HR 0.9 [95%CI 0.88–0.98]).

Conclusion

Most patients with IBD eventually require maintenance therapy. Lack of maintenance treatment is more common in UC. Nevertheless, a third of patients with CD and one quarter with UC who had no medical treatment at six months from diagnosis remained untreated for five years, especially in older patients with CD and those who did not require induction therapy, suggesting milder disease.
DOP62 Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy
Authors: Chanchlani N , Lin S , Thomas A , Hamilton B , Nice R , Chee D , Kennedy N , Goodhand J , Ahmad T
Published: May 2021

Background

Anti-TNF (aTNF) treatment failure in patients with IBD is common. International guidelines recommend switching out of class when aTNF drug levels are therapeutic and within class with an immunomodulator when aTNF drug levels are suboptimal and associated with antibody development. We sought to define the: 1) risk of immunogenicity to a second aTNF stratified by immunogenicity to the first aTNF and 2) rates of drug persistence to a second aTNF in patients with pharmacodynamic or immunogenic failure of their first aTNF drug.

Methods

We performed a retrospective cohort study across 32 UK hospitals. 870 patients (444 male, 630 (72%) Crohn’s disease) who had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to November 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgeries, and was identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic failure was defined as treatment failure despite adequate drug levels.

Results

Patients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (63% vs 40%, p = 0.004), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (33% vs 19%, p = 0.002) (Fig 1). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).

There was no difference in drug persistence to second aTNF in patients with pharmacodynamic and immunogenic treatment failure (Fig 2). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second aTNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Fig 3).

Conclusion

Immunogenicity to the first aTNF was associated with immunogenicity to the second aTNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second aTNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second aTNF at 5 years in both groups, suggesting switching in-class may be appropriate irrespective of the cause of treatment failure to first aTNF.
DOP82 Corticosteroid-free remission of Ulcerative Colitis with filgotinib maintenance therapy: Post hoc analysis of the phase 2b/3 SELECTION study
Authors: Loftus E , Vermeire S , Feagan B , Yun C , Hsieh J , Liu X , Zhao S , Moerch U , Sandborn W J , Hibi T
Published: May 2021

Background

Filgotinib (FIL) is a once-daily, oral, preferential Janus kinase 1 inhibitor in development for the treatment of inflammatory bowel disease. FIL for the treatment of moderately to severely active ulcerative colitis (UC) was evaluated in the phase 2b/3 randomized, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Long-term use of corticosteroids (CS) is associated with significant side effects. The aim of this post hoc analysis was to assess the CS-sparing effects of FIL in the SELECTION study.

Methods

Patients (18–75 years old) with moderately to severely active UC were randomized (2:2:1) to receive FIL 100 mg (n = 564), FIL 200 mg (n = 507) or PBO (n = 280) once daily orally for up to 11 weeks (induction study). At week 11, FIL induction responders were rerandomized 2:1 to continue their induction FIL dose or to receive PBO (maintenance study). CS use was kept stable up to week 14, at which point mandatory CS tapering occurred. CS could be resumed during the maintenance study; however, if the baseline CS dose was exceeded this was considered treatment failure. In this post hoc analysis, CS-free remission was defined as remission at week 58 (endoscopic subscore ≤ 1, rectal bleeding subscore = 0 and ≥ 1-point decrease in stool frequency subscore to achieve 0 or 1) without systemic or localized CS use that was indicated for UC in the previous 1, 3, 6 or 8 months.

Results

The baseline characteristics of patients in the maintenance study were similar across treatment groups (Table 1). Of the 92 patients receiving CS at maintenance baseline (week 11; maintenance week 0) who received FIL 200 mg during the maintenance study, 25 (27%) were in remission at week 58 and had been continuously CS-free for at least the previous 6 months (Table 2). The proportion of CS-free remitters in the FIL 200 mg group was consistently higher than with PBO (Table 2). In patients taking CS at maintenance baseline who had continued CS-use post baseline, lower median prednisone dosing was observed with FIL 200 mg than with PBO throughout the maintenance study (maximum difference at week 34 [maintenance week 23]: 5.0 mg vs 13.8 mg) (Figure 1). In SELECTION, a total of 199 patients received FIL 200 mg in the maintenance study, of whom 74 (37.2%) were in remission at week 58; of these 74 patients, 69 (93.2%) were continuously CS-free for at least the previous 6 months (Figure 2).

Conclusion

In this post hoc analysis of SELECTION maintenance study data, FIL 200 mg was effective in reducing and eliminating CS use through to week 58 in patients with moderately to severely active UC. The vast majority of patients taking FIL 200 mg who were in remission at week 58 had not taken CS in the previous 6 months.
DOP85 Corticosteroid-free efficacy and safety outcomes in patients receiving tofacitinib in the OCTAVE Sustain maintenance study
Authors: Vavricka S R , Greuter T , Cohen B L , Reinisch W , Steinwurz F , Fellmann M , Guo X , Lawendy N , Paulissen J , Peyrin-Biroulet L
Published: May 2021

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. Here, we report corticosteroid-free efficacy and safety among patients (pts) who received oral corticosteroids at baseline of the maintenance study (OCTAVE Sustain).

Methods

Pts with clinical response following OCTAVE Induction 1&2 who were re-randomised to receive placebo or tofacitinib 5 or 10 mg twice daily (BID) in OCTAVE Sustain, and who were receiving oral corticosteroids at baseline of OCTAVE Sustain, were included. Corticosteroid tapering was mandatory at the beginning of OCTAVE Sustain. Steroid-free (not requiring any treatment with corticosteroids for ≥4 weeks prior to the visit) rates of remission, endoscopic improvement and clinical response were assessed at Week 24 and/or Week 52. The association between baseline characteristics and steroid-free efficacy outcomes was evaluated using logistic regression. Safety outcomes were stratified by tofacitinib dose and steroid-free remission status.

Results

Of 593 pts entering OCTAVE Sustain, 289 had oral corticosteroid use at baseline. Of these, 101 (34.9%) received placebo and 188 received tofacitinib (101 [34.9%] 5 mg BID; 87 [30.1%] 10 mg BID) in OCTAVE Sustain. Among pts receiving oral corticosteroids on Day 1 of OCTAVE Sustain, the mean dose (mg/day [standard deviation], prednisone equivalent) received was 15.8 (6.2), 14.9 (6.2) and 14.4 (6.0) in the placebo, tofacitinib 5 mg BID and tofacitinib 10 mg BID groups, respectively. At Week 24 or Week 52 of OCTAVE Sustain, there was a significant treatment effect for tofacitinib 5 or 10 mg BID vs placebo for steroid-free efficacy endpoints (Table 1). Prior immunosuppressant failure was associated with lower odds of achieving steroid-free remission at Week 52 of OCTAVE Sustain (odds ratio [OR] 0.47 [95% confidence interval (CI) 0.23, 0.95]), while prior tumour necrosis factor inhibitor (TNFi) failure status only had a limited effect, which was not statistically significant (OR 0.53 [95% CI 0.27, 1.02]). Oral corticosteroid dose received at baseline of OCTAVE Sustain did not affect the likelihood of achieving steroid-free remission at Week 52. Adverse events of special interest were infrequent (Table 2). Discontinuations were numerically higher among pts without steroid-free remission (Table 2).

Conclusion

For pts with baseline oral corticosteroid use in OCTAVE Sustain, the odds of achieving steroid-free efficacy endpoints were significantly higher for tofacitinib 5 or 10 mg BID compared with placebo. Prior TNFi failure was not associated with lower odds of achieving steroid-free remission at Week 52. There were no apparent differences in safety by steroid-free remission status. Data interpretation is limited by small pt numbers.
P234 Association between anti-TNFα drug levels and drug-induced lupus in patients with Inflammatory Bowel Disease
Authors: Muñoz-Villafranca C , Irabien M , Hernandez-Aretxabaleta N , Arreba P , Ortiz de Zárate J , Garcia-Gomez C , Aresti U , Bilbao A , Irigoyen M , Garcia-Vivar M L
Published: May 2021

Background

Drug-induced lupus (DIL) has been described as an adverse event of an immunological nature, in relation to treatment with anti-TNFα drugs. It is considered as a manifestation uncommon in patients with inflammatory bowel disease (IBD).

The main objective of the study was to know the prevalence of DIL, the main characteristics and the management of IBD patients. The secondary objetive was to identify predictive factors related to the pathology.

Methods

We conducted a retrospective study, between January 2017- March 2020, in patients with IBD treated with anti-TNFα drugs during this time, in a single center. The information was obtained from the clinical history of the hospital. Patients with different degrees of data incompleteness were dismissed.

Although there are no accepted diagnostic criteria, diagnosis was based on the criteria proposed by De Bandt: (i) the presence of immunologic abnormalities: ANA+ and/or anti-dsDNA+; (ii) at least two clinical features; (iii) clear temporal association with exposure to the anti-TNFα.

The serum concentration of Infliximab (IFX) was considered optimal within the interval 3–7 μg/mL2. For Adalimumab (ADA) the optimal interval was 5–8 μg/mL3.

Results

We identified 248 patients with anti-TNFα therapy. 15 of them were dismissed due to incomplete data.

We found 8 patients with a DIL diagnosis (3.34%). The manifestations of DIL occurred after a mean of treatment duration of 29.63 months. The clinical features of DIL included arthritis (87.5%), fatigue (75%), fever (25%), vasculitis, cutaneous manifestations, and nephropaty (12.5%) each. All patients required specific treatment and in 7 of them (87.5%) the anti-TNFα drug was discontinued followed by complete clinical resolution in all of them.

Patients with DIL had a higher prevalence of suboptimal serum concentration of anti-TNFα drug than the rest of the patients (83.33% versus 29.89%, p = 0.012). In addition, the combination therapy with immunomodulators (IMM) was less frequent in the DIL group (0% versus 64.37%, p = 0.003). Antinuclear antibodies (ANA) had a higher prevalence in DIL cases (100% versus 25.36%, p>0.001).

No differences were found regarding the type of disease (CD versus UC), duration of anti-TNFα treatment, previous treatment with another anti-TNFα or with the type of anti-TNFα (IFX versus ADA).

Conclusion

The prevalence of DIL in IBD patients undergoing anti-TNFα treatment could be even higher than described due to the lack of knowledge of the disease and the absence of clearly reported diagnostic criteria. The DIL does not seem to be related to the type of disease, or the type of anti-TNFα. Suboptimal serum concentrations of anti-TNFα, as well as monotherapy treatment (without IMM) could be related to the development of DIL.
P271 Evolving Targets in Ulcerative colitis: Defining Disease Clearance in the VARSITY Study
Authors: Danese S , Schreiber S , Loftus E , Colombel J F , Peyrin-Biroulet L , Agboton C , Lindner D , Lirio R , Sands B
Published: May 2021

Background

In VARSITY, the first head-to-head randomized controlled trial of biologics, vedolizumab (VDZ) was superior vs adalimumab (ADA) in achieving clinical remission (CR) at Week 52 in patients (pts) with moderate to severe ulcerative colitis (UC).1 Current treatment goals in UC are based on clinical symptoms and endoscopy, with histologic improvement considered an aspirational goal.2-4 In pts with CR in VARSITY, greater treatment differences between VDZ and ADA at Week 52 were seen in endoscopic improvement and histologic response. Here, data from VARSITY were used to define disease clearance: a novel composite outcome in UC comprising clinical and endoscopic remission plus minimal histologic disease activity.

Methods

VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial of treatment with VDZ (300mg IV Q8W) vs ADA (40mg SC Q2W) maintenance after induction. Pts were randomized in a treat through design, and no dose escalation was allowed. For these analyses, based on pts who completed the study until Week 52, disease clearance was defined as a composite outcome based on 1) CR: partial Mayo score ≤2 and no individual subscore >1 (excluding sigmoidoscopy subscore); 2) endoscopic improvement: endoscopic subscore ≤1; and 3) absence of active histologic disease (minimum histological disease activity [MHDA]): Robarts Histology Index (RHI) <5. Treatment failure was defined as discontinuation from treatment or completion of treatment but failure to achieve any of CR, endoscopic improvement, or MHDA. The rates of disease clearance and failures were compared between treatment groups and stratified by presence of inflammatory burden at baseline: C-reactive protein ≥5 mg/L and fecal calprotectin >100 µg/g.

Results

More pts in the VDZ treatment group than the ADA group achieved disease clearance at Week 52 (VDZ: 112/383, 29.2%, 95% CI 24.7-34.1 vs ADA: 63/386, 16.3%, 95% CI 12.8-20.4). Compared with treatment failures (VDZ: 92/383, 24.0% vs ADA: 134/386, 34.7%, Table 1), disease clearers had lower C-reactive protein (CRP) baseline mean values (7.4mg/L and 6.4mg/L vs 13.6mg/L and 9.4mg/L for disease clearers vs treatment failures, for VDZ and ADA, respectively). Fewer pts with inflammatory burden at baseline (CRP ≥5 mg/L and fecal calprotectin >100 µg/g) achieved disease clearance (Fig 1). Baseline corticosteroid use was more frequent in ADA disease clearers (42.9%) compared with VDZ disease clearers (32.1%).

Conclusion

Disease clearance is a novel and achievable composite outcome that is achieved by almost one third of pts in the VDZ treatment group in VARSITY. Analyses are ongoing to further characterize the trajectory leading to disease clearance as well as the role of baseline characteristics.
P376 Improving stress and fatigue in a real-world setting among patients with Inflammatory Bowel Disease through a digital platform
Authors: Oddsson S , Gunnarsdottir T , Johannsdottir L , Amundadottir M , Frimannsdottir A , Ylanne K , Molander P , Islind A , Oskarsdottir M , Thorgeirsson T
Published: May 2021

Background

Fatigue is one of the most prominent and disabling symptoms reported by adult patients with inflammatory bowel disease (IBD). Also, stress is perceived by these patients as one of the main causes of IBD flare-ups. Therapeutic guidelines call for effective disease assessment, early intervention, and personalized care using a treat-to-target approach which may be hard to achieve through standard care. Providing patients with effective self-management strategies and patient support programs (PSPs) via a digital platform to complement standard care, may be optimal for improving fatigue and reducing stress.

The objective of this study was to perform a preliminary test of engagement and effectiveness of a newly developed 16-week PSP delivered via the digital platform Sidekick Health.

Methods

Participants were recruited via Finnish IBD patient association websites and social media (advertisements through Facebook and Instagram). Participants entered baseline characteristics upon program signup. Platform engagement was automatically tracked, and participants reported stress, energy levels (fatigue), and quality of sleep through the platform.

Results

An intention to treat (ITT) sample included 205 participants. Eighty people completed the required outcome measures during weeks 12-16 (completers). More women than men took part (61.5%) with the average age of 40.3 years (mean, SD=11.5) and average BMI of 27.9 (mean, SD=6.0). ITT analyses showed significant improvements in ratings of stress (t(204)=3.488; p<0.01, percentage change=-9.52%), and energy levels (t(204)=-2.381; p<0.05, percentage change=4.60%). No significant difference was observed in quality of sleep (t(204)=-1.368; p=0.173). For completers (n=80), significant improvements were observed for stress (t(79)=4.574; p<0.01, percentage change=-23.26%) and energy levels (t(79)=-2.440; p<0.05, percentage change=9.48%) but not for quality of sleep (t(79)=-1.319; p=0.191).

Conclusion

These results indicate that participation in the Sidekick Health PSP for IBD has significant positive effects on patient-reported stress and energy levels. These findings are promising and provide initial support for using this digital platform for supplementing standard care for IBD patients.
P394 Serological biomarkers of type III and IV collagen remodeling predict and monitor infliximab treatment response in patients with Inflammatory Bowel Disease
Authors: Sorokina Alexdóttir M , Bourgonje A R , Asser Karsdal M , Bay-Jensen A C , Faber K N , Loveikyte R , van Dullemen H M , Visschedijk M C , Festen E A M , Weersma R K , Dijkstra G , Mortensen J H
Published: May 2021

Background

Immunotherapeutic drugs such as anti-TNFα antibodies have greatly improved the treatment of inflammatory bowel disease (IBD). However, up to 20-40% of patients still fail to respond to therapy as the pattern of disease is variable. Better patient profiling could increase treatment response and improve quality of life. The aim of this study was to assess whether serological biomarkers reflecting tissue formation and different forms of basement membrane (BM) degradation could monitor or predict treatment response to anti-TNFα in patients with Crohn’s disease (CD) and Ulcerative Colitis (UC).

Methods

Using competitive ELISA, serum biomarkers of matrix metalloproteinase (MMP)-mediated type IV collagen degradation (C4M), T-cell related collagen degradation (C4G) and type III and IV collagen formation (PRO-C3, PRO-C4) were measured in 89 patients (CD=63, UC=26) receiving infliximab (IFX) induction therapy. Disease activity was defined by composite assessment of the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC together with physician’s global assessments (PGA). Clinical remission (HBI <5, SCCAI <2.5) was assessed at week 14. Logistic regression models adjusted for confounding factors (CD: age of diagnosis and ileoceacal surgery, UC: steroid use at week 14) were used to examine prediction value for treatment response.

Results

In patients with CD, baseline ratios of C4M/C4G (P<0.001, AUC=0.95) and PRO-C4/C4G (P< 0.05, AUC=0.92) were significantly lower at baseline in responders (n=57) compared to non-responders (n=6). PRO-C3 levels were increased at week 14 in CD patients responding to therapy compared to those not responding (P<0.01, AUC=0.93). Finally, UC patients responding to treatment (n=19) showed decreased levels of C4M/C4G (P<0.01, AUC=0.96) at week 14 compared to non-responders (n=7).

Figure 1: A) Serum levels at baseline or week 14 between non-responders and responders for CD and UC. B) ROC curves showing discriminative capacity of the biomarkers (ratios) between responders and non-responders.

Conclusion

Increased baseline ratios of type IV collagen remodeling (C4M/C4G, PRO-C4/C4G) in serum predict treatment response to IFX in patients with CD, whereas PRO-C3 may serve as a monitoring tool reflecting tissue restoration. The ratio between MMP- and granzyme B-mediated degradation of type IV collagen (C4M/C4G) in serum was elevated in non-responders compared to responders and may serve as non-invasive tool to monitor treatment response in patients with UC. Together, these biomarkers may help reveal different profiles of ECM turnover and inflammation and thus aid in better prediction and monitoring of response to anti-TNFα treatment.
P396 Acceptance of switch, patient satisfaction and adverse events after switch from adalimumab originator to biosimilar SB5 in patients with Inflammatory Bowel Disease in a real-life setting
Authors: De Somer T , Deprez N , Baert D , Deceuninck M , Huys I , Mattens V , Sterckx A , Vanden Branden S , Vanderstraeten E , Vandervoort J , Van Heddegem N , Dewint P
Published: May 2021

Background

SB5 is approved as a biosimilar of the adalimumab originator. However, data on patient acceptance of switch from originator to biosimilar, patient satisfaction, adverse events and nocebo effects are lacking, especially in the inflammatory bowel disease (IBD) population. We sought to elucidate these issues in a real-life switch IBD population.

Methods

IBD patients, in clinical remission or stable response, treated with adalimumab originator in 2 Belgian centers were offered to participate in this phase IV, interventional trial. Switch was voluntary and was offered after being informed about biosimilars. Satisfaction with the switch and local discomfort after injection (within and after 30 minutes) was semi-quantitatively (visual analogue scales (VAS)) assessed at baseline and 8 weeks, 6 months and 12 months after switch. Reasons for non-switch, discontinuation and adverse events were documented.

Results

An acceptance of switch rate of 79.3% was observed. Fifteen patients reported 22 reasons for refusal; the most common were fear for a flare (n = 8), ease to stay on the originator (n = 4) and absence of trust in biosimilars (n = 3). No patient-related demographic factors associated with refusal of switch could be defined. By month 12, 28 patients discontinued SB5 for several reasons; the most frequent being high anti-adalimumab antibodies at baseline (n = 5), secondary loss of response (n = 3), injection site pain (ISP) (n = 8) and other adverse events (n = 10) not causally related to SB5. At month 12 after switch, 74.5% of the study population was still treated with SB5 (table 1). The median VAS for local discomfort up to 30 minutes after injection of the originator was 1/10 and increased significantly to values between 2 and 3/10 at the different time points on SB5 (p < 0.001 for all) (table 2). However, the median VAS for local discomfort after 30 minutes was between 0 and 1/10 at all time points, which was not significantly different compared to the originator. Nevertheless, satisfaction with the decision to switch was high and remained stable over the different time points with a median VAS between 7 and 8/10, which was not significantly different compared to baseline.

Conclusion

After being well informed, the great majority of patients treated with adalimumab originator is willing to switch to biosimilar SB5. The rate of satisfaction under treatment with SB5 is high and remains stable over time. The most important reasons for discontinuation were adverse events, which could be mostly attributed to the nocebo effect and to ISP. Of note, patients in general report a higher, temporary, local discomfort within 30 minutes after injection with SB5.
P419 Psychological acceptability of surgery in patients with ulcerative colitis after total colectomy
Authors: Itabashi M , Hirano Y , Saito T , Inoue M , Uchida K , Arai K , Minakuchi E , Ishihara H , Onizawa R , Hirayama A , Araki K , Kimura H , Kunisaki R
Published: May 2021

Background

The purpose of surgery for patients with ulcerative colitis (UC) is to save their lives and improve their quality of life (QOL). However, deciding whether to undergo surgical intestinal resection is among the most difficult decision that patients with UC may be required to make during the disease course. Although clinical outcomes and changes in QOL after total colectomy have been reported, few studies have investigated the psychological acceptability or subjective feelings among patients after surgery. This study aimed to evaluate the psychological acceptability of surgery among patients with UC who underwent total colectomy.

Methods

A cross-sectional single questionnaire survey for patients with UC who underwent colectomy was conducted from October 2019 to February 2020 at five Japanese IBD centres in Japan. According to the opinions of seven physicians specialising in IBD and a clinical psychologist, we created a questionnaire using a 10-point visual analog scale (VAS) consisting of 20 questions related to surgical acceptance and concerns related to UC. We asked patients to answer the questionnaire by recollection of the pre- and postoperative periods. The VAS scores before surgery were described by the patients looking back on their recollections. Pre- and post-surgical VAS scores were compared using Wilcoxon’s rank sum test. Cases under 6 years old at colectomy and patients followed for more than 10 years after surgery were excluded.

Results

There were 71 cases, and the median age at surgery was 31.0 [range 9–75] years. The median time since surgery was 4.0 [range 0–10] years, and the valid response rate was 93 percent. Compared with pre-operatively, psychological acceptability of surgery significantly improved significantly after total colectomy (p < .001). The median scores for psychological acceptability of surgery were 5.1 (0–10) and 8.6 (0.3–10) before and after surgery, respectively. Scores improved in more than 90% of the patients. Subscores for a sense of loss of the colon, shame related to excretion, and dietary satisfaction improved significantly after surgery (p < .0001).

Conclusion

We examined for the first time the psychological acceptance of surgery among patients with UC who underwent total colectomy. We found that many of the emotional, physical, and social questions associated with UC improved after surgery.
P426 Health-Related Quality of Life and Work Productivity in patients with moderate-to-severe Inflammatory Bowel Disease in Argentina: Data from the RISE AR study
Authors: Correa G J , Yantorno M , Olivera Sendra P , Lasa J S , Lubrano P , Balderramo D C , Zubiaurre I , Ruffinengo O , Brion L , Leonardi D B , El-Hakeh J , Guimaraens P N , Sambuelli A
Published: May 2021

Background

Patient-reported outcomes (PROs) are increasingly recognized as complementary to objective markers of disease activity, yet evidence on PROs in inflammatory bowel disease (IBD) in the real-world setting in Latin America is limited. Herein, we describe health-related quality of life (HRQoL) and work productivity and activity impairment (WPAI) of IBD patients (pts) in Argentina.

Methods

RISE-AR (NCT03488030) was a non-interventional study with a cross-sectional evaluation and a 3-year retrospective chart review conducted in 7 centres in Argentina (12/2018-05/2019) to assess healthcare resource utilisation, HRQoL and WPAI. Adult pts (≥18 yr old) with a previous diagnosis of moderate-to-severe (Mod/Sev) ulcerative colitis (UC) or Crohn′s disease (CD) based on clinical, endoscopic or imaging criteria ≥6 months prior to enrolment, were included. HRQoL (IBD Questionnaire [IBDQ], 5-dimensional EuroQoL measure [EQ5D]) and WPAI instruments were administered at screening. Disease activity at enrolment was classified as Mod/Sev (Harvey Bradshaw Index ≥8 or partial Mayo Score ≥5) vs. “no-or-mild” (No/Mild). A p-value ≤0.05 was considered statistically significant (Mann-Whitney U test).

Results

Overall, 246 pts were included (41.1% CD; 58.9% UC). At enrolment, median (range) age (years) was 39.5 (18.2-74.0) for CD (51.2% female) and 41.9 (18.0-80.4) for UC (55.2% female) pts; 20 pts (9.3% CD; 7.7% UC; excluding 4 ostomized pts) had Mod/Sev disease activity. During the previous 3 years, 17.8% (CD) and 1.4% (UC) of pts required ≥1 surgery, and 33.7% (CD) and 21.4% (UC) were hospitalized. No/Mild pts showed significantly higher overall HRQoL scores (mean±SD) vs. Mod/Sev pts in CD (IBDQ: 178.1±35.4 vs. 140.0±43.5, p<0.05; EQ5D [visual analogue scale]: 75.7±1.8 vs. 64.4±5.5, p<0.05) and UC (180.2±32.9 vs. 132.9±43.8, p<0.001; 77.1±1.3 vs. 57.7±5.3, p<0.001), respectively. Activity impairment was reported by 55.4% and 58.6% of CD and UC pts, respectively, while 37.9% and 43.9% of CD and UC employed pts (67 CD, 92 UC; Mod/Sev: 5 CD, 6 UC) reported work impairment. Mod/Sev IBD pts had higher absenteeism (30.8% vs. 6.3%, p<0.05) and presenteeism (20.0% vs. 7.5%, p=0.149) vs. No/Mild pts. Female gender, surgeries and hospitalizations were associated with lower QoL in the overall IBD population.

Conclusion

This is the first study to evaluate QoL and WPAI in IBD pts in Argentina. Pts with Mod/Sev activity showed impaired QoL and WPAI compared to No/Mild pts. Whilst, less than 10% of IBD pts had Mod/Sev disease activity at enrolment, nearly 60% of the overall IBD population reported either work or activity impairment. Thus, disease activity scores alone may fail to assess the real burden of IBD, suggesting a relevant role for PROs in disease management.
P435 The impact of perianal fistula in Crohn’s disease on quality of life: results of a patient survey conducted in Europe
Authors: Spinelli A , Yanai H , Lönnfors S , Girardi P , Milicevic S , Carvello M , Maroli A , Avedano L
Published: May 2021

Background

Perianal fistulas (PAF) in Crohn’s disease (CD) may impair social performance, sexual function, life activities and overall patients’ quality of life (QoL). Patient experience is important in the treatment decision making and in providing adequate support. Despite the clinical relevance, few studies have addressed the patient perspective on the impact of PAF and complex PAF (CPAF) in CD on QoL.

Methods

A questionnaire assessing the impact of PAF on QoL was developed by patient representatives and medical experts addressing diagnosis, symptoms and QoL including close relationships, social life, sexual activity and working life. CD patients with and without PAF were invited to participate. The self-selective anonymous survey was available in 11 languages and accessible on the European Federation of Crohn’s & Ulcerative Colitis Associations’ (EFCCA) website and national inflammatory bowel disease patient association websites from 15 July to 31 December 2019.

Results

Of 820 respondents with CD (67.2% women; mean age 40.8 years), 532 (64.9%) reported PAF in CD of which 272 (51.1%) reported CPAF. PAF/CPAF patients had experienced and were currently experiencing more anal pain and perianal leaking than CD patients (Figure). On a 10-point scale, PAF/CPAF patients reported a greater impact on overall QoL (6.91 vs 6.18, p<0.001), relationships with family and friends (5.54 vs 4.78, p<0.001), relationship with partner (5.24 vs 4.11, p<0.001), social life (5.65 vs 4.97, p=0.001) and working life (5.54 vs 5.12, p=0.02) than CD patients. PAF/CPAF patients reported feeling more unhygienic, uncomfortable, and guilty about their condition toward family and friends than CD patients. They also found it more difficult to talk with family and close friends about their condition. PAF/CPAF patients avoided having sex, ended relationships, had arguments with partner, felt inadequate to partner, avoided dating and had their partner refuse having sex more often than CD patients. Furthermore, these patients were unable to play sports, carried a personal hygiene kit, were aware of access to clean toilets, and had changed profession/career due to their condition more often (Figure).

Conclusion

From the patients’ perspective, PAF/CPAF in CD severely impacts patients’ overall QoL, social and sexual relationships and work life. These results are important to consider when tailoring treatment strategy and patient services in a multidisciplinary way to address individual patient needs.
P440 First results of the BELCOMID study: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)
Authors: Geldof J , Truyens M , Sabino J , Ferrante M , Lambert J , Lapeere H , Hillary T , Van Laethem A , De Vlam K , Verschueren P , Lobaton T , Vermeire S
Published: May 2021

Background

It has been suggested that 100% of SARS-CoV2 infections leads to development of specific IgG antibodies that remain detectable for a long period of time. Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors (JAKi) for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with cytokine storm and humoral immune response against COVID19. We investigate the seroprevalence of SARS-CoV2 IgG in relation to previous exposure to COVID19 and ongoing IMID treatment in a Belgian, real-life population of IMID patients.

Methods

A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. Between 17/12/2020 and 29/02/2021, all patients with IMIDs of the gut (Crohn’s disease (CD), ulcerative colitis (UC)), joints (rheumatoid arthritis, psoriatic arthritis, spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Both patients under conventional treatment and/or TIMT were included. Patients were asked to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (SARS-CoV-2 IgG Abbott – Architect kit®). Statistical analyses were performed with SPSS26.

Results

In total 2166 IMID patients consented to take part. Of these, 1913 responded to the survey, including 218 dermatology patients, 415 rheumatology patients and 1217 IBD patients (64.7% CD, 34.3% UC, 1% undifferentiated colitis). There were 372 patients (19.5%) who reported having experienced symptoms suggestive of COVID19 (Fig. 1). Fatigue (61.3%), headache (48.1%), throat ache (46.9%) and dry cough (38.7%) were most frequent. Gastrointestinal symptoms such as diarrhoea or abdominal pain were present in less than 20.0% (Fig. 2). Ninety-six IMID patients (5.04%) had a positive SARS-CoV2 PCR test on nasal or throat swab. In 44/96 (45.8%) anti-SARS-CoV2 IgG seroconversion was confirmed. There was no significant difference in seroconversion rate between patients treated with TIMT compared to conventional therapy (P=0.192). Of the seroconverted group, 75.0% were treated with TIMT. The interval between reported positive PCR date and serology test date ranged from 3 to 24 weeks with a mean of 10 weeks. Of all survey responders, 25 were hospitalized for respiratory symptoms since 01/02/2020, six of these had positive SARS-CoV2 PCR.

Conclusion

Prevalence of COVID19 symptoms and number of confirmed COVID19 cases by PCR in this cohort of IMID patients remain low regardless of treatment modality. There was no significant difference in SARS-CoV2 IgG seroconversion rate between TIMT or conventional treatment in patients with positive PCR.
P478 Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard-dose subcutaneous maintenance therapy: an observational multicentre study
Authors: Olmedo-Martín R , Martín-Rodríguez M D M , Lorenzo-González L , Lázaro-Sáez M , Lopez-Vico M , Hernández-Martínez Á , Argüelles-Arias F , Vázquez-Morón J M
Published: May 2021

Background

Ustekinumab is a human monoclonal antibody that targets interleukin (IL)-12 and IL-23 and it is effective for the treatment of Crohn’s disease (CD). However, a group of patients will not respond or over time will experience loss of response (LOR) to ustekinumab. Evidence supporting the effectiveness of ustekinumab dose escalation for LOR is scarce. The aim of this study was to assess the effectiveness of ustekinumab dose escalation in a cohort of patients with active CD

Methods

Multicentric retrospective cohort study conducted in 5 tertiary Andalusian centers. Patients with active CD who received a standard-dose intravenous (IV) induction and at least one subcutaneous (SC) ustekinumab dose were included. All enrolled patients received dose escalation by either shortening the interval between the maintenance doses to every 4 or 6 weeks, IV reinduction or a combination of strategies. The primary outcome of the study was to assess corticosteroid (CS)-free clinical remission (HBI ≤4) at week 16. Secondary outcomes were CS-free clinical response (decrease of HBI ≥ 3 points from baseline) at week 16 and on the last follow-up, CS-free clinical remission on the last follow-up and ustekinumab persistence after dose escalation

Results

A total of 84 patients were included (54,8% female, median duration of CD 13,5 years). A 47,5% of the patients had history of previous abdominal surgery and 55% had been treated with 2 or more biologics. Patients were dose-escalated after a median treatment duration of 37 weeks (IQR 23–54). The most frequent type of dose escalation was the 90 mg every 4 weeks regimen (58%). A 25% of the patients were on concomitant immunomodulators at escalation. At week 16 from dose escalation the proportion of patients in CS-free response was 50/84 (59%) including 18/84 (21,4%) in CS-free remission. Follow-up data beyond week 20 were available for 61/84 patients (72.6%). On the last follow-up visit, 29/61 (47,5%) patients responded to treatment without concomitant CS of which 19/61 (31%) were in CS-free clinical remission. Systemic CS were discontinued in 21/44 (47.7%) patients who were on CS at the time of dose escalation. Ustekinumab was discontinued in 14/84 (17%) of the patients due to clinical non-response (ustekinumab persistence was 81% at 14 months of follow-up). Adverse events following dose escalation were reported in 4 of the 84 patients (7.7%), none of them were serious.

Conclusion

Dose escalation of ustekinumab maintenance was effective in over 50% of the patients and the treatment persistence was high. This strategy should be considered in patients who are not responsive or have LOR to ustekinumab on an 8-week dose maintenance interval