bluuebunny/crossref_metadata_2025 huggingface dataset:
P636 Real-world clinical effectiveness and safety of vedolizumab and ustekinumab in biologic-naïve patients with Crohn’s disease: Results from the EVOLVE Expansion study
Authors: Ferrante M , Christensen B , Bressler B , Brett N , Bassel M , Kamble P , Adsul S , Gianchetti L , Scharl M
Published: January 2023

Background

This study evaluated real-world clinical effectiveness and safety of vedolizumab (VDZ), a gut-selective α4β7-integrin inhibitor and ustekinumab (UST), an IL-12/23 p40 inhibitor, as first-line biologic treatment (Tx) for patients (pts) with Crohn’s disease (CD).

Methods

The EVOLVE Expansion study (NCT05056441) was a multicenter, observational, retrospective cohort study in biologic-naïve pts with CD (≥18 years old) who initiated VDZ or UST Tx in Australia, Belgium or Switzerland from 2016 to 2021. Data were collected from Tx initiation to initiation of chart abstraction, death or loss to follow-up, whichever came first. The time to event analysis was conducted using the Kaplan-Meier method and cumulative rates of clinical response, remission, mucosal healing and Tx persistence were estimated over 12, 24 and 36 months. Serious adverse events (SAEs), serious infections (SIs), CD exacerbations and CD-related surgeries were also evaluated. Inverse probability of treatment weighing was used to balance demographic and clinical characteristics across treatment groups.

Results

623 biologic-naïve pts with CD (VDZ 347, UST 276) from 31 sites were included. Baseline characteristics are presented in Table 1. Cumulative rates over 36 months were similar between VDZ- and UST-treated pts for clinical response (VDZ 82.0%, UST 84.1%; p=0.87) and clinical remission (VDZ 88.3%, UST 88.5%; p=0.67) (Table 2). Mucosal healing rates were significantly higher in VDZ- versus UST-treated pts (VDZ 91.3%, UST 87.4%, p=0.02), and treatment persistence was higher in UST-treated pts over 36 months (VDZ 70.6%, UST 80.3%; p=0.03). In VDZ cohort, 54 SAEs (including SIs) and 12 SIs occurred in 35/347 (10.1%) and 9/347 (2.6%) pts, respectively, while in UST cohort, 53 SAEs (including SIs) and 5 SIs occurred in 27/276 (9.8%) and 2/276 (0.7%) pts, respectively. There were no significant differences in the risk of CD exacerbations (HR 1.01; 95% CI, 0.68-1.49; p=0.98) and CD-related surgeries (HR 1.80; 95% CI, 0.69-4.73; p=0.23) between VDZ- and UST-treated pts.

Conclusion

In real-world setting, clinical response and clinical remission were similar between VDZ and UST in biologic-naïve pts with CD. However, over 36 months mucosal healing was higher in the VDZ-treated pts, and Tx persistence was higher in UST-treated pts.
P647 Outcomes following the use of vedolizumab first line versus second line in Ulcerative Colitis: a single centre experience
Authors: Almas S , Al-Talib I , Rahman C , Ansari M , Jones J , Slater J , King D , De Silva S
Published: January 2023

Background

With the introduction of an increasing number of biological therapies for Ulcerative Colitis (UC), decisions regarding the sequencing of treatment continues to dominate current management strategies. In this single centre study, we assessed outcomes in patients with UC following first line treatment with the α4β7 integrin blocker vedolizumab (VDZ) therapy vs second line VDZ therapy following anti-Tumour Necrosis Factor (anti-TNF) exposure.

Methods

All patients exposed to VDZ either first line or second line were identified via our Inflammatory Bowel Disease (IBD) registry. Data was collected retrospectively between June 2015 and June 2021. Baseline demographics, disease extent and activity scores, treatment continuation, and colectomy rates were analysed over a 52-week period.

Results

A total of 100 patients were included in the study, age (median [IQR]) 52 [37-64] years; 52% male 48% female). VDZ as first line biologic included 38 patients, age (median [IQR]) 51 [34-65] years; 50% male and 50% female). The VDZ as second line (Ant-TNF exposed) group included 62 patients, age (median [IQR]) 52 [38-61] years; 53% male and 47% female). The Anti-TNF exposed group included infliximab 26 (43.3%), adalimumab 22 (35.5%), golimumab 12 (19.2%) and both infliximab and adalimumab 2 (3%).

Disease extent (Montreal classification: E1:proctitis, E2: left-sided or E3: extensive disease) in the VDZ first line group (E1 (13.1%), E2 (61.6%) and E3 (26.3%)) versus VDZ second line (E1 (11.3%), E2 (61.3%) and E3 (27.4%)).

In the VDZ first line group (38 cases), the outcomes at 52 weeks were: Treatment continuation 24 (63%), colectomy 2 (5%) and treatment switch in 12 (32%) to infliximab (4), Adalimumab (3), Ustekinumab (4) and Tofacitinib (1).

In comparison, the Anti-TNF exposed group (62 cases) outcomes at 52 weeks were: Treatment continuation 46 (74%), colectomy 5 (8%) and treatment switch in 11 (18%) to Adalimumab (2), Ustekinumab (4) and Tofacitinib (5).

A total of 7 of patients underwent colectomy during the 52 week follow up period. By 52 weeks, 94.8% (36/38) were colectomy free in the VDZ first line group versus 92% (57/62) in the anti-TNF exposed group, which was not statistically significant (odds ratio (OR) of having a colectomy in the VDZ1st line group vs the VDZ 2nd line group was 0.61(p=0.58)).

Conclusion

Our study evaluated real-world treatment continuation and colectomy-free outcomes for VDZ as first and second line biologic therapy (Anti-TNF exposed) in patients with ulcerative colitis and confirmed its effectiveness in both treatment groups.
P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?
Authors: Carbery I , Lin S , Chanchlani N , Janjua M , Nice R , McDonald T J , Bewshea C , Kennedy N A , Ahmad T , Goodhand J R , Selinger C P
Published: January 2023

Background

Lower serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio has been linked to non-response to treatment in a range of diseases, including in biologic-treated patients with IBD. We sought to assess whether baseline serum fT3/fT4 ratio predicted primary non-response (PNR) and non-remission to infliximab and adalimumab in patients with Crohn’s disease.

Methods

We included 997 adult participants from the Personalised Anti-TNF Therapy in Crohn’s Disease study (PANTS). Thyroid function tests, using the Roche Elecsys TSH immunoassay and T3 and T4 electrochemiluminescence assays, were measured on stored baseline samples (prior to biologic treatment). PNR, assessed at week 14, was defined as treatment failure (including IBD-related surgery), ongoing corticosteroid use, or both CRP failing to fall to ≤3 mg/L, or by 50% from baseline, and HBI failing to fall to ≤4, or by 3 points. Non-remission, assessed at week 54, was defined as either CRP of > 3mg/L or HBI of >4 points, ongoing corticosteroid therapy, or exit for treatment failure.

Results

Serum fT3, fT4 and TSH concentrations were similar in infliximab (n=549) and adalimumab treated (n=448) patients. Baseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27 - 0.34] vs 0.32 [0.28 - 0.36], p<0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25 - 0.33] vs 0.32 [0.29 - 0.36], p<0.001).

Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (OR 0.51, 95% CI 0.31 – 0.85, p = 0.009), however when stratified by drug and adjusted for variables known to be associated with PNR, low fT3/fT4 ratio remained associated with PNR for adalimumab, but not infliximab. After excluding patients treated with corticosteroids at baseline, there was no difference in fT3/fT4 ratio in those who experienced PNR compared to those who did not (PNR: [128/630] 0.31 [0.28 – 0.35] vs no PNR: [502/630] 0.32 [0.29 – 0.36], p = 0.095). The optimal threshold to determine PNR was 0.31 (AUC 0.57 [95% CI 0.54 - 0.61] sensitivity 0.62 [95% CI 0.41 - 0.74], specificity 0.53 [95% CI 0.42 - 0.73]).

No association was seen for baseline fT3/fT4 ratio and non-remission or changes in faecal calprotectin concentrations at week 54.

Conclusion

Lower baseline serum fT3/fT4 ratio was independently associated with female sex, higher inflammatory burden at baseline, and baseline corticosteroid use, and predicted PNR to anti-TNF therapy at week 14, but not non-remission or change in faecal calprotectin concentrations at week 54. Overall, however, the diagnostic accuracy of baseline fT3/fT4 ratio to predict PNR to anti-TNF treatment was modest, limiting its clinical utility.
P658 Comparative Efficacy and Safety of Upadacitinib Versus Tofacitinib as Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: A Matching-Adjusted Indirect Comparison
Authors: Reinisch W , Tran J , Patel K , Borruel N , Melmed G Y , Wegrzyn L , Levy G , Ilo D , Sanchez Gonzalez Y , Panaccione R
Published: January 2023

Background

Upadacitinib (UPA) and tofacitinib (TOFA) are Janus kinase (JAK) inhibitors approved for the treatment of patients (pts) with moderately to severely active ulcerative colitis (UC), but evidence on their comparative efficacy and safety is limited. This study conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) of efficacy and safety induction outcomes between UPA and TOFA.

Methods

Pts received oral UPA 45 mg once daily or PBO for 8 weeks in the phase 3 induction studies U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026), and oral TOFA 10 mg twice daily or PBO for 8 weeks in phase 3 OCTAVE 1 and 2 Induction trials (NCT01458951, NCT01465763). MAIC of efficacy outcomes was conducted for bio-naïve and bio-failure pts. These included clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore >1), clinical response per FMS (decrease from baseline in FMS ≥3 points and ≥30%, with a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), and endoscopic improvement (EI; endoscopic subscore [ES] 0 or 1). The overall population was used to assess endoscopic remission (ER; ES of 0) and safety outcomes including any adverse events (AEs), serious AEs (SAEs) and discontinuation (DC) due to AEs. Baseline characteristics of age, gender, extent and duration of disease, FMS, and corticosteroid use from UPA trials were weighted to match reported OCTAVE pts for primary efficacy outcomes, plus weight, C-reactive protein, and haemoglobin for ER and safety outcomes. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and TOFA.

Results

The MAIC used data from 961 and 977 UPA pts for primary efficacy and ER/safety outcomes, respectively, and 1,139 TOFA pts. A greater proportion of pts receiving UPA vs TOFA in bio-naïve and bio-failure groups achieved clinical remission, clinical response, and EI (p <0.05, Table 1). PBO-adjusted differences between UPA vs TOFA for clinical remission, clinical response, and EI were 14.6%, 23.0%, and 25.1%, respectively, for bio-naïve pts and 8.5%, 27.7%, and 14.3% for bio-failed pts. ER was also higher in UPA vs TOFA (8.6% difference, p < 0.001). AEs and SAEs were not statistically different between UPA and TOFA pts, but proportion of DC due to AEs were lower in UPA vs TOFA (p < 0.05, Table 2). NNT/NNH analysis showed a favorable benefit-risk profile of UPA vs TOFA.

Conclusion

Pts with moderately to severely active UC achieved greater clinical efficacy and similar safety during induction treatment with UPA compared to TOFA based on MAIC, suggesting a favorable benefit-risk profile of UPA in the JAK class.
P669 Improving Crohn’s disease stricture dilation outcome: Effect of repeated dilation, needle knife stricturotomy, and ongoing active inflammation
Authors: Schulberg J D , Hamilton A L , Wright E K , Holt B , Sutherland T , Ross A L , Vogrin S , Kamm M A
Published: January 2023

Background

Traditionally Crohn’s disease strictures have been treated by a single endoscopic balloon dilation (EBD), repeated only for obstructive symptom recurrence. We postulated that scheduled repeated EBD may result in greater dilation effect than a single EBD; and that needle-knife stricturotomy (NKSt) may be a valuable salvage intervention in patients with strictures.

Methods

In this prospective observational study, patients with endoscopically accessible and short (<5cm), symptomatic Crohn’s disease stricture were assessed clinically (using an Obstructive Symptom Score [OSS]) and by imaging (colonoscopy, MRI and IUS). All patients had drug treatment optimized to decrease inflammation. Patients were treated with 3 serial balloon dilatations each 3 weeks apart, single EBD, or needle-knife stricture incision. The primary endpoint was improved OSS at 6m. Secondary outcomes; ability to endoscopically pass the stricture, treatment failure / surgery, stricture morphology on imaging, and safety.

Results

Twenty-one consecutive patients were included in the analysis. Of these 17 (81%) were receiving treatment with a biologic therapy. Median stricture length at baseline was 20mm (IQR 20mm) and median estimated stricture diameter was 8mm (IQR 3mm). 18 (86%) had visible ulceration. Of the 21 patients 11 (52%) underwent more than one EBD, 5 (24%) had ≥1 NKSt and 5 (21%) underwent a single EBD. Four of the 21 patients (19%) strictures were passable before endoscopic treatment. All procedures were technically successful. 14/21 (67%) had improvement in OSS at 6m, including 8/11 (73%) with 3 serial EBD, 4/5 (80%) with NKSt and 2/5 (40%) patients undergoing a single EBD. Two patients required surgery. At 6m, 3/8 (38%) who had repeat dilations, 4/5 (80%) who had NKSt, and 2/5 (40%) having a single EBD had a passable stricture. All 4 patients with highly elevated stricture inflammation (stricture magnetic resonance index of activity [MaRIA] score ≥20) at the 6m MRI had a non-passable stricture at study endpoint, whilst 9/12 (75%) were passable when stricture MARIA was <20 (P=0.019). No major complications occurred.

Conclusion

Endoscopic stricture treatment was safe and technically successful in all patients with accessible Crohn’s disease strictures and was associated with symptom improvement in most. Progression to surgery in this symptomatic and advanced disease was low at 6m. The highest rates of symptom improvement were seen in patients who had NKSt. Lesser stricture inflammation on MRI was associated with a better outcome, suggesting that controlling inflammation is important in preventing stricture recurrence after dilation. NKSt should be considered when balloon dilation is not possible or has failed, as a salvage treatment alternative to surgery.
P672 Switching out of class or to another anti-TNF agent is the most effective strategy in IBD patients with immunogenicity against anti-TNF antibodies
Authors: Anjie S , Hanžel J , Gecse K B , D'Haens G R , Brandse J F
Published: January 2023

Background

Immunogenicity to anti-TNF agents is associated with loss of response in inflammatory bowel disease (IBD). However, the efficacy of different strategies to restore favourable pharmacokinetics and/or clinical response upon the detection of anti-drug antibodies (ADA) has not been widely studied. We evaluated the success of different strategies leading to clinical remission with ADA disappearance (in patients continuing the same anti-TNF), in patients with IBD.

Methods

IBD patients with ADA to infliximab or adalimumab were identified through an electronic database search at a single tertiary centre between 2004 and 2021. ADA were measured using a drug-sensitive assay at Sanquin laboratories. Data concerning clinical, biochemical and endoscopic activity, medication and surgery were retrospectively and systematically collected by reviewing clinical records. Criteria for success of a strategy were clinical remission 1 year after ADA detection without further change in strategy combined with disappearance of ADA (in patients continuing the same anti-TNF).

Results

Two-hundred-and-fifty-five IBD patients (206 Crohn’s disease, 46 ulcerative colitis, 3 IBD-unclassified, 149 female) were included, 129 patients were diagnosed to have ADA against infliximab and 126 against adalimumab. At baseline, median ADA titer was 77 AU/ml (IQR 25-350), 50.2% of patients were in clinical remission. Groups were as follows: 1) 81/255 (32%) conservative management, 2) 102/255 (40%) optimization of the same anti-TNF, 3) 72/255 (28%) switch to another anti-TNF or biological class. Switch to another anti-TNF or out of class was the most successful strategy in terms of improvement of clinical remission (from 19.4% at ADA detection to 69.4% at 1 year, p<0.001). Patients that continued with the same dose anti-TNF or discontinued all biological therapy after ADA detection were often in clinical remission at baseline, but deteriorated significantly in the following year (22.7%, P=0.004). Anti-TNF dose intensification with concomitant addition/optimisation of immunomodulators was the fastest (median 3 months (IQR 2-4.5), p=0.004) and most effective (in 73% of these patients, p=0.007) strategy to suppress ADA to undetectable levels compared to anti-TNF dose intensification or immunomodulator optimization alone.

Conclusion

Switching to another anti-TNF or out of class switch is the most successful strategy to regain and maintain clinical remission upon detection of ADA. Intensification of anti-TNF dosing with concomitant optimisation of immunomodulatory therapy is the fastest strategy to suppress ADA.
P678 Ustekinumab therapy improves the nutritional status in patients with Crohn's Disease. A prospective study
Authors: Bertani L , D'Alessandro C , Fornili M , Coppini F , Zanzi F , Carmisciano L , Geri F , Baiano Svizzero G , Ceccarelli L , Mumolo M G , Baglietto L , Bellini M , Costa F , De Bortoli N
Published: January 2023

Background

Patients with Crohn’s disease (CD) display high rates of nutritional deficiencies and metabolic imbalances, primarily due to mucosal damage induced by inflammation. In particular, the loss of lean muscle mass configures a condition known as sarcopenia, which is not necessary associated with a low Body Mass Index (BMI). The presence of sarcopenia has been associated with a worst outcome of IBD. At present, no studies evaluated the impact of Ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition assessed by Bioelectrical Impedance Assay (BIA) in patients with CD. In particular, we evaluated phase angle, which represents the most clinically established impedance parameter and it might be considered as a reliable and optimal marker of nutritional status.

Methods

We prospectively enrolled all consecutive CD patients treated with UST at our center, following the current guidelines. BIA was performed at baseline and at week 48, assessing Body Cellular Mass (BCM), total body water, phase angle and BMI. At the same time-points, a colonoscopy was performed in order to evaluate the therapeutic outcome in terms of mucosal healing, defined as a Simple Endoscopic Score for CD <2. We evaluated also clinical remission, defined as a Harvey-Bradshaw Index <5 at week 48.

Results

Out of 44 patients enrolled, 26 (59%) presented clinical remission and 22 (50%) achieve mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value=0.010 and 0.008 for clinical remission and mucosal healing, respectively). The same differential increase was observed for BCM (test for the interaction between time and outcome, p-value=0.037 and 0.076 for clinical remission and mucosal healing, respectively). No other significant differences were observed regarding the other BIA parameters.

Conclusion

UST therapy seems to be able to modify body composition of patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients. Our results are in line to what was shown by a previous study performed in patients with psoriasis treated with UST.
P681 Effectiveness and safety of oral Tacrolimus salvage therapy for acute severe ulcerative colitis: a retrospective study
Authors: Tamir-Degabli N , Cohen N A , Hirsch A , Fishman S , Ron Y , Thrum T , Maharshak N
Published: January 2023

Background

Calcineurin inhibitors are a therapeutic option in patients with acute severe ulcerative colitis (ASUC) failing to respond to intravenous steroids. There are limited data regarding the real world effectiveness of tacrolimus in this setting. We describe our experience with tacrolimus in a tertiary IBD center.

Methods

This retrospective study includes patients who were hospitalized at our center with ASUC between 2018-2022 and received tacrolimus salvage therapy. We collected demographic, clinical, and laboratory data. The primary endpoint of this study was clinical response to tacrolimus therapy leading to patient discharge. Secondary endpoints were safety of therapy and long-term effectiveness.

Results

Sixteen patients received tacrolimus therapy; 15 patients with UC and 1 patient with indeterminate colitis. The median age was 36 (interquartile range (IQR) 29-51), median disease duration 9 years (IQR 4.5-12), 10 (69%) were females, 11 (69%) had pan-colitis; 12 (75%) had previous biologic exposure. The median CRP was 44.46 mg/L (IQR 20.1-155), median albumin 3.2 g/dL (IQR 2.9-3.7).

15 patients (94%) responded to tacrolimus and were discharged, 1 patient failed to respond and underwent colectomy. Mean tacrolimus level during induction was 12.48 ng/ml (± 4.5). Following discharge, 1 patient had an exacerbation secondary to poor adherence and underwent colectomy within 2 months. 12 patients were transitioned to biologic therapy (7 vedolizumab, 3 ustekinumab, 2 adalimumab, 1 golimumab) and 1 patient to azathioprine. All 13 patients avoided colectomy with a median follow-up of 5.5 months (IQR 3-12). One patient was lost to follow up. Regarding safety, 10 patients had mild electrolyte disturbance requiring oral supplementation. No other adverse events were observed and no patient discontinued therapy due to adverse events.

Conclusion

Oral tacrolimus salvage therapy shows effectiveness and acceptable safety profile in patients with ASUC. The oral nature of this therapy provides an attractive therapeutic option in this setting.
P682 Development of anti-ustekinumab antibodies is an independent factor associated to loss of response to ustekinumab therapy in IBD patients
Authors: Roblin X , Nancey S , Bastide L , Veyrard P , Bischetti G , Berger A E , Barrau M , Paul S
Published: January 2023

Background

Monitoring of antibodies (ADA) under ustekinumab therapy in routine practice is not recommended in IBD patients.

Aim of study

to investigate the relationship between ADA detected by a drug-tolerant assay and loss of response to therapy in a cohort of IBD patients treated with ustekinumab.

Methods

This was a retrospective study enrolling consecutively all adult patients with moderate to severe active IBD and having a follow up period of at least 2 years after ustekinumab induction. Loss of clinical response was defined as CDAI > 220 or HBI > 4 for CD and partial Mayo subscore > 3 for UC associated with the decision to modify disease management or treatment.

Results

Ninety patients were included (78 CD and 12 UC, mean age 37 years). Median levels of anti-ustekinumab antibodies (AUA) were significantly higher in patients with LOR compared with those in responder patients (15.2 µg/mL-eq CI (7.9-21.5) and 4.7 µg/mL-eq CI (2.1-10.5), respectively; p=0.04). The area under the ROC curve (AUROC) for AUA in predicting LOR was 0.76. The optimal cut-off point capable to accurately identify patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80 % and specificity of 85 %. In multivariate analysis, serum AUA ≥ 9.5 µg/mL-eq (HR=0.84), prior vedolizumab exposition (HR=0.78) and azathioprine (HR=3.78) exposures were the only independent factors associated with subsequent clinical response to ustekinumab therapy.

Table 1 : univariate and multivariate analysis to isolate factors associtaed with subsequent clinical response to ustekinumab therapy

Conclusion

In our real-life cohort, AUA was identified as an independent predictor of LOR and subsequent drug failure to treatment
P698 Role of an exclusion diet (reduced disaccharides, saturated fats, emulsifiers, red and ultraprocessed meats) in maintaining the remission of chronic inflammatory bowel diseases in adults
Authors: Preda C M , Istratescu D , Manuc T , Nitescu M , Louis E , Manuc M , Stroie T , Diculescu M
Published: January 2023

Background

Inflammatory bowel diseases (IBD) are a main focus in current research with diet being an emerging therapeutic line due to its links both in onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission.

Methods

One hundred seventeen adult IBD patients in remission (64 patients with Crohn’s disease- CD and 53 patients with ulcerative colitis- UC) were randomized at their own will to a 6-months exclusion diet (n=32) or a habitual diet (n=85). Dietary patterns, clinical activity of the disease and inflammatory markers were assessed at baseline and at the end of dietary intervention.

Results

The acceptance rate of the exclusion diet in our cohort was 27.35% (30% in UC and 20% in CD). The exclusion diet and control populations were similar, except for immunosuppressive treatment (only 30% of patients in the exclusion diet group had an immunomodullator compared to 70% in the control group (p-value <0.001)).

The clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, 3 patients had clinically active disease (1 patient with UC and 2 patients with CD) and 80 patients maintained the clinical remission state (96.4%) (p-value = 0.278). Figure 1 is depicting the remission rates in different patient groups. Regarding biochemical markers, erythrocyte sedimentation rate (ESR) at baseline was higher in the exclusion diet arm: 31 (5-62) than in the control arm 14.5 (4-48) (p-value=0.011), but six months after, the groups were similar (p-value = 0.440). Fecal calprotectin at baseline was higher than 300 micrograms/gram in 30% of cases in the exclusion diet arm and in 25.8% of cases in the control arm (p-value = 0.774). Six months after, 50% of cases had a higher fecal calprotectin (>300 micrograms/gram) in the intervention arm and only 20.5% in the control arm (p-value = 0.033).

Figure 1. Maintenance of clinical remission 6 months after intervention

Conclusion

We found a better trend of sustained clinical remission in patients who follow an exclusion diet.

However, the threshold for statistical significance was not achieved.

The clinical study continues, these are preliminary data.

There is also a trend of improvement in ESR in the intervention group, but the levels of fecal calprotectin did not improved.
P701 A time-to-event model relating infliximab trough concentrations to the risk of relapse after extending the infusion interval
Authors: Kantasiripitak W , Outtier A , Thomas D , Sabino J , Vermeire S , Ferrante M , Dreesen E
Published: January 2023

Background

Extending the infliximab infusion interval has been attempted in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who sustained treatment response following an earlier interval shortening. We aimed to identify predictors of sustained remission after infliximab interval extension.

Methods: Data from 30 adult patients (17 CD, 13 UC), who underwent infliximab interval extension following earlier interval shortening, were collected from a single-centre database search. All patients were in steroid-free clinical (two-item patient-reported outcome [PRO2] ≤1 [UC] and ≤8 [CD]) and biological (C-reactive protein [CRP] <5 mg/L or faecal calprotectin [FC] <250 mg/kg) remission at interval extension. Time-to-relapse was modelled using a time-to-event (TTE) model with loss of steroid-free clinical and biological remission being the event of interest (NONMEM7.5). Various hazard functions were explored, and disease type, time-varying infliximab concentrations and infliximab clearance were investigated as predictors of the relapse hazard risk. The infliximab clearance was calculated using weighted averaging of the estimates of 18 population pharmacokinetics models.1

Results

In total, 37% of patients (n=11) remained relapse-free until one year after infliximab interval extension (Figure 1). A time-constant (exponential) hazard model proved best to describe the relapse data of patients with CD (Figure 2, Table 1). The Gompertz hazard model best described the data of patients with UC, with the relapse hazard risk increasing over time. Patients with CD had an overall higher relapse hazard risk than patients with UC. For patients with UC, the infliximab trough concentration was negatively related to the relapse hazard risk and was included in the model using a sigmoidal inhibitory Emax function. Also, in patients with UC, a higher infliximab clearance was associated with an increase in the relapse risk. The infliximab clearance was also a predictor of the relapse hazard risk, but its effect could not be precisely estimated.

Conclusion

Patients with CD had a higher relapse risk than patients with UC. Only in patients with UC, the hazard risk increased with time, but this risk was lower when the infliximab trough concentration increased. No exposure-response relationship was observed in patients with CD. Results of this exploratory analysis should be interpreted with care and prospective confirmation is awaited (MODIFI study; NCT04982172).2

1Kantasiripitak W. et al. CPT PSP. 2022

2Sheiner LB. et al. CPT. 1997
P702 Clinical and biomarker remission is maintained after switch from monthly dosed intravenous to subcutaneous maintenance treatment with vedolizumab in Inflammatory Bowel Disease
Authors: Pintar S , Hanžel J , Smrekar N , Koželj M , Drobne D , Kurent T , Štabuc B , Novak G
Published: January 2023

Background

Background: Subcutaneous (SC) formulation of vedolizumab (VDZ), a gut selective integrin antagonist used for treatment of inflammatory bowel disease (IBD), has proven effective and safe in clinical trials after intravenous (IV) induction. However, it is not clear if patients can be effectively switched from IV maintenance treatment to SC. We aimed to assess real-world efficacy of switch from IV to SC formulation and to investigate if baseline maintenance regimen (every 8 weeks (q8) versus every 4 weeks(q4)) impacts outcome after switch.

Methods

Methods: In this observational study at a tertiary referral centre, we enrolled 126

prospectively followed consecutive adult patients with IBD who were switched to SC VDZ maintenance treatment. We included patients after IV induction (2 or 3 infusions) and patients who switched from IV maintenance treatment q8 and q4. SC VDZ dosing was 108 mg every 2 weeks regardless of the previous IV regimen. Clinical (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) and partial Mayo score (pMayo) for ulcerative colitis (UC)) and biochemical disease activity (CRP, fecal calprotectin (FC)) were assessed at the time of switch and at first and second follow-up. HBI<5 and pMayo<2 were considered clinical remission. CRP <5mg/L and FC<150mg/kg were considered biomarker remission.

Results

Results: In total 126 patients (40% CD, 60% UC) were switched to SC vedolizumab. Demographics and baseline characteristics are presented in Table 1. Median time to 1st follow up (FU) was 14,5 weeks (IQR 12-26) and median time to 2nd FU was 40 (IQR 36-52) weeks. From all patients, 8/126 (6%) discontinued SC VDZ treatment, 5 of them due to endoscopically active disease (2 in IV induction group, 3 in q4 group), 1 had dysplasia and required surgery (IV induction group), two others (both q8 group) discontinued on their wish. In patients who continued SC treatment clinical and biomarker remission appears to be maintained at 1st and 2nd FU. Clinical and biomarker outcomes are presented in Table 1. Vedolizumab concentrations were 16.9, 24.6 and 13.0 at baseline, 27.0, 25.3 and 25.2 at 1st FU and 25.5, 34.6 and 22.1 at 2nd FU in the q8, q4 and IV induction group, respectively.

Conclusion

Conclusion: The results of this real-world study suggest maintenance of clinical and biomarker remission in patients switched from IV to SC vedolizumab. Baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.
P703 Real world experience of the transition from the intravenous to subcutaneous formulation of vedolizumab in inflammatory bowel disease: A review of current data
Authors: Agboton C , Kamble P
Published: January 2023

Background

Vedolizumab (VDZ), a gut selective antilymphocyte trafficking anti-α 4β 7 integrin monoclonal antibody indicated for the treatment of IBD. After a 3 doses induction, maintenance can be achieved with a standard 8-weekly (Q8W) regimen, or–at any time during the maintenance– patients can be transitioned to 108 mg subcutaneous (SC) formulation at a standard 2 weekly (Q2W) regimen.

Methods

This was a literature review to identify real-world studies on the transition from the IV to SC VDZ. The Pubmed and Embase databases were searched up to October 2022 to identify publications on real-world data on the transition from IV to SC VDZ.

Results

In total, 9 studies were identified with a total of 1,323 IBD patients in the UK (5 studies), Norway, Sweden, Belgium and The Netherlands1-9. Two prospective studies reported no loss of effectiveness based on disease activity scores of VDZ after the IV-SC transition 1,2, along with maintenance of baseline status (status at the time of transition) reported in 84% of patients1. Biomarkers stability, including fecal calprotectin and C-reactive protein, were reported in three studies3-5. Persistence with VDZ treatment following IV-SC transition was 96% at 6 months and 89% at 12 months in one study3, while another study reported persistence of 86% at 6 months6. A preference for the SC formulation by patients was reported 59% and 56% in two studies7,8, with time savings and fewer hospital visits recorded as the main reasons for preference of the SC formulation7. Multivariate analysis of patient characteristics in two studies7,8 revealed no factor associated with preference for VDZ SC other than younger age in one study8. The most frequently reported adverse events with VDZ SC were injections site reactions: 15% and 18% in two studies1,5, with transient severe injection site reactions reported in 1% of patients in one study3.

Conclusion

Real-world data on IBD patients who transitioned from IV to SC VDZ showed no change in effectiveness, with a majority preferring the SC formulation due to time savings and the transition leading to fewer hospital visits. Safety of VDZ SC was generally comparable with that of IV VDZ.

References:

1. Ventress E et al J Crohn’s Colitis 2022;16:911-21

2. Volkers A et al Aliment Pharmacol Ther 2022;56:1044-54

3. Bergqvist V et al Aliment Pharmacol & Ther 2022;55:1389-1401

4. Mclean M et al Gut 2022;71:A58-A59

5. Wiken T et al J Crohn’s Colitis 2022;16:i378-79

6. Lim S et al J Crohn’s Colitis 2022;16:i499-i500

7. Alice H et al J Crohn’s Colitis 2022;16:i410

8. Asnong K et al J Crohn’s Colitis 2022;15:S608-9 9. Maw F et al Gut 2021;70:a91
P705 Switching from intravenous to subcutaneous infliximab: clinical and patient experience outcomes
Authors: Nowell E , Laird S , Bailey E , Brownson E , Saunders J , Seenan J P , Smith G , Macdonald J
Published: January 2023

Background

Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic.

Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes.

Methods

The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch.

Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8).

Results

31 patients consented to switch; F:M = 17:14. The majority of patients (16) had Crohn’s disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24.

At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score <5 or partial Mayo score <2), 96% had CRP <5 mg/Land 87% had FCP <250µg/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline.

Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort.

15 patients submitted CUCQ-8 scores, of these 7 patients’ scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline.

Conclusion

Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.
P711 Decreased steroid exposure and disease-related hospitalizations in patients with newly diagnosed inflammatory bowel disease in the era of newer biologic agents – A multi-centre experience in Singapore
Authors: Yeo G D D , Qui M , Pak W C W , Tan C K , Tay S W , Lim C T T , Tan T K M , Ong W C , Lim T G , Ng Y T V , Wong S Y A , Salazar E
Published: January 2023

Background

The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has drastically improved the clinical outcomes of patients with both Crohn’s Disease (CD), and Ulcerative Colitis (UC). However, data of clinical outcomes in newly diagnosed IBD in the era of biologics in recent decades remains limited. We aim to compare the clinical outcomes of newly diagnosed IBD patients in Singapore between the era of conventional biologics (originator Anti-TNF) with those diagnosed during the era of newer biologics over a 14-year period.

Methods

This is a multi-centre retrospective observational cohort study. Baseline demographics and treatment histories were obtained from the registries of two tertiary centres in Singapore. Clinical outcomes such as systemic steroid use, IBD-related hospitalizations and IBD-related surgeries were obtained. Anti-TNF, anti-integrin, anti-IL-12/23 and biosimilars were approved for IBD management in 2006, 2016 and 2018 respectively in Singapore. Patients diagnosed with IBD from 2006 to 2019 were included and further subdivided into two cohorts: Pre-2013 (from 2006 to 2012) and post-2013 (from 2013-2019).

Results

During the study period, 725 patients [CD: 331 (46%), UC: 394 (54%), pre-2013: 291 (40%), post-2013: 434 (60%)] were newly diagnosed with IBD. 625 (86%), 475 (65%), and 241 (33%) patients were exposed to 5-ASA, immunomodulators, and biologics respectively. Compared to the pre-2013 cohort, patients from the post-2013 cohort had less exposure to 5-ASA [277 (95%) vs 348 (80%), p<0.001], and immunomodulators [219 (75.3%) vs 256 (58.9%), p< 0.001].

In patients who were started on biologics, the overall median time from diagnosis to biologic initiation was 2.8 (1.1 – 6.3) years. 196 (81.3%) patients started on biologics were initiated from 2016 onwards. Median time to biologic initiation was shorter for the post-2013 cohort, compared to the pre-2013 cohort. (1.4 (0.5 – 2.8) vs 6.9 (4.3 – 9.1) years, p<0.001). This was observed in both patients with CD [1.2 (0.3 – 2.4) vs 6.9 (4.7 – 8.6) years, p<0.001] and UC [2.3 (0.9 – 3.4) vs 7.1 (3.8 – 9.2) years, p<0.001].

Steroid exposure and IBD-related hospitalizations were higher in the pre-2013 cohort [(OR 1.7 (95% 1.2 – 2.5, p=0.001) and (OR 1.6 (95% 1.2 – 2.3, p=0.003) respectively], but no difference was found in the number of IBD-related surgeries between both cohorts (OR -0.02 (95% -0.4 – 0.4, p=0.934).

Conclusion

Paralleled with earlier, and increased initiation of biologic agents, there is significant reduction of steroid exposure and IBD-related hospitalizations in patients newly diagnosed with IBD in the era of newer biologics, despite a reduction in 5-ASA and immunomodulator exposure.
P713 Proactive therapeutic infliximab monitoring during induction phase in inflammatory bowel disease
Authors: Gonzalez Vivo M , Carballo Martinez N , Padulles Zamora N , Colominas Gonzalez E , Murciano Gonzalo F , Abril Rodriguez L , Marquez-Mosquera L
Published: January 2023

Background

Therapeutic drug monitoring (TDM) of infliximab (IFX) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is increasingly used in clinical routine, although proactive TDM is still controversial. Nevertheless, disease activity and drug clearance are higher at the induction phase leading to an increased risk of inadequate drug exposure and treatment failure.

The aim of the study was to evaluate the efficacy of the implementation of an early proactive TDM strategy, comparing clinical remission (CR) and biochemical remission (BR) at week 14 and 52, and endoscopic improvement (EI) between two groups.

Methods

Retrospective cohort study conducted in an Inflammatory Bowel Disease (IBD) unit of a tertiary care hospital. Biologic-naïve patients diagnosed of CD or UC who initiated IFX from 2019 to 2021 (p-TDM group) and from 2016 to 2019 (no-TDM group) were included.

In the p-TDM group, proactive IFX trough levels and antidrug antibodies were measured since week 2 and dose adjustment since week 6 was performed using a previously validated population pharmacokinetic model (Fasanmade et al. Clinical Therapeutics 2011).

In the no-TDM group, dose escalation was performed considering symptoms, blood, or stool results.

CR was defined as Harvey-Bradshaw Index <5 in CD and partial Mayo clinic score <3 in UC. BR was stablished as fecal calprotectin (FCP) <150 mcg/g or c-reactive protein <0.5 mg/dL. EI was defined as lack of ulcerations in CD and Mayo endoscopic score 0-1 in UC. A combined variable to evaluate objective remission (OR) at week 52 was defined as: FCP <150 mcg/g or EI in UC, and EI or radiologic improvement (MRI) in CD.

Moreover, surgery, hospitalization and treatment discontinuation rates were compared between both groups.

Results

30 patients were included in each group: 13 UC, 16 CD and 1 IBD unclassified. There were no statistical differences in baseline characteristic between groups (table 1).

Outcomes at week 14 and 52 are shown in table 2.

At week 14, CR rate was significantly higher in p-TDM than in no-TDM (86.7% vs 56.7%, p=0.01). Although BR rate at week 14 was numerically higher in p-TDM, it did not achieve statistical significance (61.1% in p-TDM vs 50.0% in no-TDM, p=0.59). However, limitations in blood and stool collection were considerable at this timepoint.

During first year, hospitalizations tend to be fewer in p-TDM group. There were no statistically differences in CR and BR or in EI between groups at week 52. Although OR rate was higher in p-TDM than in no-TDM, it did not reach statistical significance (60.9% vs 33.3%, p=0.06).

Conclusion

Proactive TDM during induction phase, especially in naïve patients, could be a useful tool to obtain optimal IFX trough levels and to classify correctly primary failure.
P714 Mucosal healing in CD with vedolizumab versus other biologics: endoscopic outcomes during long-term routine care in a multinational observational study
Authors: Siegel C , Sebastian S , Siegmund B , Zhou J , Jones S , Adsul S , Louis E
Published: January 2023

Background

Mucosal healing (MH) is considered an important treatment target for patients (pts) with moderate to severe Crohn’s disease (CD). The aim of this analysis was to evaluate rates of MH achieved during treatment with vedolizumab (VDZ) or other biologics in pts with CD who underwent endoscopic assessments during routine clinical practice in a long-term observational study across a number of multinational study centres.

Methods

Data were analysed from a long-term prospective, multicentre, post-authorization safety study (PASS; NCT02674308, EUPAS6469) cohort of pts with CD. This secondary outcome was evaluated in pts initiating treatment with VDZ or other biologics, including infliximab, adalimumab and ustekinumab. Pts received treatment under routine standard of care with clinical decisions at the discretion of treating physicians, treatment could be modified or changed without the need to withdraw from the study. For pts with available endoscopy data, rates of MH (simple endoscopy score [SES-CD] ≤ 2) at baseline and 12-months were compared in biologic-naïve or biologic-experienced pts treated with VDZ versus other biologics.

Results

MH was analysed in pts with CD who had endoscopic assessment. In those pts who were biologic-naïve and had baseline endoscopy (VDZ n=76, other biologics n=239), MH rates at baseline were 11.8% (9/76) versus 12.1% (29/239), respectively. After 12-months’ treatment, MH rates in biologic-naïve pts who had endoscopy data at month 12 (VDZ n=48, other biologics n=108) were 70.8% (34/48) in VDZ-treated pts versus 60.2% (65/108) in pts treated with other biologics (Table 1). In pts who received biologic treatment prior to study entry (biologic-experienced) and had baseline endoscopy (VDZ n=151, other biologic n=146), MH rates at baseline were 11.9% (18/151) versus 16.4% (24/146), and 51.1% (45/88) versus 31.4% (27/86) after 12 months of treatment in the VDZ and other biologic cohorts, respectively.

Conclusion

These real-world data from a multinational observational study show that VDZ was effective at achieving MH, particularly as a first-line biologic treatment, and also in biologic-experienced pts.