The Impact of Vedolizumab on Pre-Existing Extraintestinal Manifestations of Inflammatory Bowel Disease: A Multicenter Study

Author(s):  
Guilherme Piovezani Ramos ◽  
Christina Dimopoulos ◽  
Nicholas M McDonald ◽  
Laurens P Janssens ◽  
Kenneth W Hung ◽  
...  

Abstract Background There are limited data on how vedolizumab (VDZ) impacts extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). The aim of this study was to determine the clinical outcomes of EIMs after initiation of VDZ for patients with IBD. Methods A multicenter retrospective study of patients with IBD who received at least 1 dose of VDZ between January 1, 2014 and August 1, 2019 was conducted. The primary outcome was the rate of worsening EIMs after VDZ. Secondary outcomes were factors associated with worsening EIMs and peripheral arthritis (PA) specifically after VDZ. Results A total of 201 patients with IBD (72.6% with Crohn disease; median age 38.4 years (interquartile range, 29-52.4 years); 62.2% female) with EIMs before VDZ treatment were included. The most common type of EIM before VDZ was peripheral arthritis (PA) (68.2%). Worsening of EIMs after VDZ occurred in 34.8% of patients. There were no statistically significant differences between the worsened EIM (n = 70) and the stable EIM (n = 131) groups in term of age, IBD subtype, or previous and current medical therapy. We found that PA was significantly more common in the worsening EIM group (84.3% vs 59.6%; P < 0.01). Worsening of EIMs was associated with a higher rate of discontinuation of VDZ during study follow-up when compared with the stable EIM group (61.4% vs 44%; P = 0.02). Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients. Conclusions Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S412-S414
Author(s):  
U Kopylov ◽  
J Burisch ◽  
S Ben-Horin ◽  
F Braegger ◽  
A Fernández-Nistal ◽  
...  

Abstract Background Vedolizumab is an α4β7 integrin monoclonal antibody indicated for moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC). There are limited data on how vedolizumab impacts extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD). The aim of the study was to analyse the effect of vedolizumab on EIM in a real-world cohort of IBD patients. Methods A multicentre retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands and Switzerland. Adult patients with moderately to severely active IBD and concurrent active EIM with at least 6 months follow-up after vedolizumab initiation (index date) were enrolled. Improvement of EIM was defined as absence of symptoms (resolution) or partial response (reduction of symptoms). Results 99 patients were included (UC: 44, CD: 55); the majority of active EIM at index were musculoskeletal (Table 1). Median disease duration at index was 9 (IQR: 3-19) years and 77% of patients had been exposed to 1+ biologic. Overall, after 6 and 12 months of vedolizumab, 37% and 50% of EIM respectively were reported as improved, 22%, 25% as stable (no change) and 1% and 3% as worsened (Table 2), missing values were 5% and 4%, respectively. Median time since first EIM improvement was 0.5 months (Figure 1). At 6 and 12 months, 48% (10/21) and 33% (6/18) of patients experienced clinical response/remission of their IBD, respectively. Vedolizumab treatment persistence at 12 months was 83% overall (Figure 2). Adverse Events were reported for 18% patients; 96% of them non-serious. Conclusion Vedolizumab treatment was associated with an improvement in 37% and 50% of EIM at 6 and 12 months, respectively, in a real-world IBD cohort.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 201-202
Author(s):  
Z Chattha ◽  
R Chattha ◽  
S Reza ◽  
M Moradshahi ◽  
M Fadida ◽  
...  

Abstract Background The relationship between older age and extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) remains unknown. Aims This study aims to determine whether older age is associated with increased risk of EIMs in IBD patients. Methods This was a retrospective study of IBD patients seen at the McMaster University Medical Centre, in Hamilton, ON, Canada from 2012–2020. Patients were identified to have the primary outcome of interest if their gastroenterologist documented the presence of any EIM either during the baseline assessment or during the period of follow up. The independent variable, age at start of follow-up, was dichotomized into two categories age >=40 vs. <40.Prior knowledge in combination with forward selection was used to develop a logistic regression model. The variables utilized for the forward selection model included gender, disease duration, and current biologic use. Results A total of 995 IBD patients (625 with CD) were considered for the regression analysis, all for whom the EIM status was recorded. Out of the 995 patients, 270 patients reported at least one EIM – 99 with arthritis/arthralgia, 79 with dermatologic manifestations, 16 with ophthalmic manifestations, 30 with liver manifestations, and 116 with other EIMs. A univariate regression analysis foundincreased odds of EIMs in older patientsas compared to younger patients (odds ratio (OR) 1.41 (95% CI, 1.05 – 1.89)). In the multivariate regression analysis, current biologic use was found to have a significant relationship with odds of having EIMs (OR 1.49; 95% CI, 1.06 – 2.09). After adjustment for biologic use, patients aged 40 or over had 1.46 times higher odds of having EIMs (95% CI 1.03 – 2.05). A sub-analysis of individual EIM categoriesdid not show a significant association with older age. Conclusions Older age is associated with increased risk of EIMs in IBD patients. Patients with EIMs were also more likely to be treated with biological therapies. Clinicians should inquire about the presence of EIMs in older IBD patients. Funding Agencies None


BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel Heise ◽  
Charles Schram ◽  
Roman Eickhoff ◽  
Jan Bednarsch ◽  
Marius Helmedag ◽  
...  

Abstract Background Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up. Methods The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan–Meier method and risk factors for recurrence determined by Cox regressions. Results General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn’s disease (CD, 1/19, HR = 1.0, p = 0.021). Conclusion IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD.


2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 126-127
Author(s):  
E Lytvyak ◽  
L A Dieleman ◽  
A J Montano-Loza

Abstract Background Previous studies suggested that patients with autoimmune hepatitis (AIH) and inflammatory bowel disease (IBD) have poorer outcomes; however, the significance of this association is limited. Aims To describe the phenotype of AIH-associated IBD and assess the impact of IBD on the response to treatment and risk of adverse liver outcomes in patients with AIH. Methods In our retrospective cohorts, we identified patients with concomitant diagnoses of IBD and a definite AIH. The comparison cohort consisted of AIH patients matched by gender, age at diagnosis, ethnicity, and time to follow-up. Chi-square and Mann-Whitney tests were used to assess differences. Univariate analysis was performed using the Cox proportional hazards model. Results We identified a total of 16 patients (9 males, 56.3%) with AIH-associated IBD from a cohort of 6006 IBD patients (0.27%) and 357 AIH patients (4.5%). All patients were Caucasians. Twelve patients (75.0%) had ulcerative colitis with a pancolonic extent; 4 (25.0%) – Crohn’s disease: one patient had ileitis, three – ileocolitis with one having stricturing and fistulising gastroduodenal, ileocolonic and perianal disease. The median age at IBD diagnosis was 26.5 years old and varied from 2 to 53. The age at AIH diagnosis ranged from 7 to 59 years old (median 21.1) and median follow-up time was 11.1 years ranging from 11 days to 35.2 years. The matching cohort of 113 AIH-IBD- patients was comparable to the AIH-IBD+ cohort by gender (44 males, 38.9%; p=0.188), age at diagnosis (median 28.4, IQR 32; p=0.442), ethnicity, and the follow-up time (median 8.7 years, IQR 10.2; p=0.764). There was no difference in AST, ALT and ALP at diagnosis. Complete response rates were similar in AIH-IBD+ and AIH-IBD- groups (50.0% vs. 53.1%; p=0.816). The risk of developing cirrhosis and a median time to its onset did not differ significantly: 28.6% vs. 31.0% (p=0.853) and 11.8 vs. 8.2 years (p=0.359), respectively. In univariate Cox regression, IBD was not a predictor of progression to cirrhosis (HR 0.45; 95% CI 0.13–1.50; p=0.192). The risk of developing decompensation and a median time was also comparable between groups: 21.4% vs. 33.0% (p=0.384) and 18.4 vs. 9.8 years (p=0.053), supported by the Cox regression analysis (HR 0.44; 95% CI 0.13–1.48; p=0.187). The presence of IBD was not associated with higher need in liver transplant (18.8% vs. 30.1%; p=0.348), median time was slightly shorter (1.48 vs. 4.73 years; p=0.542), also evidenced by Cox regression (HR 1.40; 95% CI 0.42–4.65; p=0.578). The risk of liver-related death was also not different among the two groups (6.3% vs. 4.4%; p=0.746), and IBD was not a predictor of it (HR 1.94; 95% CI 0.17–21.69; p=0.589). Conclusions The presence of IBD in patients with AIH is rare and do not identify a subgroup of patients with worse response to treatment or poor clinical outcomes. Funding Agencies AbbVie


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S310-S310
Author(s):  
R Lev Zion ◽  
G Focht ◽  
N Asayag ◽  
D Turner

Abstract Background Bowel ultrasonography (BUS) for imaging of inflammatory bowel disease (IBD) is increasingly recognised as a prominent non-invasive tool to supplement, and in some cases replace traditional endoscopic and imaging modalities, with high sensitivity and specificity. The increasing number of gastroenterologists trained to perform BUS has transformed BUS into a bedside tool to guide routine clinical decision making and accurately monitor response to treatment. However, this process is still in its infancy in paediatric IBD. We present here data on the first 2 years of implementation of BUS performed by a paediatric gastroenterologist (RLT) at the paediatric IBD centre at Shaare Zedek Medical Center in Jerusalem. We aim to describe trends, results and clinical implications of the US studies performed during this period. Methods The electronic medical record system was searched for all BUS studies performed on IBD patients by RLT as part of his weekly IBD clinic between 2017–2019. Studies performed on other caregivers’ patients were excluded to ensure uniform documentation and nomenclature. Findings were classified as normal (wall thickness <3 mm), mild (wall thickening 3–4 mm and blood flow < Limberg 3) or significant signs of inflammation (wall thickness ≥4 mm or 3–4 mm with Limberg ≥3). Charts were reviewed to assess the impact of BUS findings on clinical management. Results A total of 83 bedside BUS studies were performed on 55 IBD patients (42 with Crohn’s – CD) during the study period, with a mean age of 15.1 ± 3.7 years. Thirty-four had one study (23 with CD), 15 had two (13 with CD) and 6 had three or more (all with CD). Overall, 32 studies were normal, 20 showed mild findings and 30 showed significant inflammation. Four studies found stenosis and one showed an abscess. Follow-up studies of initially active disease showed 10/16 (63%) with improvement, including 9/16 (56%) with sonographic remission. 22/83 (27%) studies were felt upon review to have had a direct impact on clinical decision-making. These included decisions not to switch therapy due to normal BUS despite symptoms, admission due to discovery of an abscess, decision to escalate therapy due to lack of sonographic improvement, and decision to continue adalimumab in the presence of a stricture due to favourable prognostic characteristics as per the CREOLE study. Conclusion Bedside BUS is a practical and useful tool that can be integrated into a paediatric IBD clinic, with the ability to provide relevant information in real-time and thus impact on day-to-day patient management.


2018 ◽  
Vol 53 (10-11) ◽  
pp. 1250-1256 ◽  
Author(s):  
Alvilde Maria Ossum ◽  
Øyvind Palm ◽  
Milada Cvancarova ◽  
Inger Camilla Solberg ◽  
Morten Vatn ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S468-S470
Author(s):  
A Chandrakumar ◽  
M Carroll ◽  
J deBruyn ◽  
K Jacobson ◽  
H Huynh ◽  
...  

Abstract Background Anti-tumor necrosis factor (anti-TNF) antagonists such as infliximab (IFX) are widely used for the treatment of inflammatory bowel disease (IBD). Early studies suggested that combination therapy with IFX and an immunomodulator drug (IM) such as azathioprine (AZA) or methotrexate (MTX) may help in optimising biologic pharmacokinetics, minimising immunogenicity, and improving outcomes. On the other hand, IM especially AZA, may increase infection and cancer risks with no clear evidence on long-term benefits of combination therapy. As such, stopping IM and continuation of an anti-TNF agent as a monotherapy in patients in remission seem to be a sensible strategy. However, there is no evidence to prove the efficacy of this strategy. The aim of this work was to examine frequency and factors associated with the first relapse after IM withdrawal in a cohort of children with IBD on combination therapy. Methods In a retrospective multicenter pediatric study, we determined the percentage of patients and investigated potential factors associated with the first relapse in a cohort of children and young adults with IBD on combination therapy of anti-TNF and IM after stopping IM. Cox regression analysis was used to assess factors associated with IBD relapse following IM withdrawal. Results A total of 79 patients (42, males, 62 Crohn’s disease) with 74 (93.7%) on IFX were included. In addition to the anti-TNF agent, 33 (41.8%) were on AZA and the rest were on MTX. The median duration of combination therapy was 2.0 (IQR 1.2–2.8) years. All participants were in clinical remission at the time of IM withdrawal. The median duration of follow-up after IM withdrawal was 11.0 (IQR 5.0–16.2) months. Only 8 (10.1%) patients relapsed over that period of follow-up. Age, sex, disease phenotype at diagnosis, family history of IBD, type of IM, and biochemical markers and clinical disease activity indices prior to IM stoppage did not predict a future relapse. Among those with CD on IFX who maintained remission, the median last IFX trough level before IM withdrawal was 6.25 Ug/ml (IQR: 4.04–8.70) vs. 3.8 Ug/ml (IQR: 2.40–11.6) in those who relapsed (p = 0.4). Conclusion Over short-term follow-up, the majority of children on combination therapy of IM and an anti-TNF agent remain in clinical remission after IM withdrawal.


Author(s):  
Parita Patel ◽  
Guimin Gao ◽  
George Gulotta ◽  
Sushila Dalal ◽  
Russell D Cohen ◽  
...  

Abstract Background Although several studies have associated the use of nonsteroidal anti-inflammatory drugs with disease flares in patients with inflammatory bowel disease (IBD), little is known about the impact of daily aspirin use on clinical outcomes in patients with IBD. Methods We conducted a retrospective analysis of a prospectively collected registry of patients with IBD from May 2008 to June 2015. Patients with any disease activity with daily aspirin use were matched 1:4 to controls by age, sex, disease, disease location, and presence of cardiac comorbidity. Patients with at least 18 months of follow-up were included in the final analysis. The primary outcomes of interest were having an IBD-related hospitalization, IBD-related surgery, and requiring corticosteroids during the follow-up period. Results A total of 764 patients with IBD were included in the analysis, of which 174 patients were taking aspirin. There was no statistical difference in age, gender, diagnosis (Crohn’s disease vs ulcerative colitis), disease duration, Charlson Comorbidity Index, smoking status, medication usage, or baseline C-reactive protein between groups. After controlling for covariables and length of follow-up in the entire population, aspirin use was not associated with a risk of being hospitalized for an IBD-related complication (odds ratio [OR], 1.46; P = 0.10), corticosteroid use (OR, 0.99; P = 0.70), or having an IBD-related surgery (OR, 0.99; P = 0.96). Conclusion In this single-center analysis, aspirin use did not impact major clinical outcomes in patients with IBD. Although the effect of aspirin use on mucosal inflammation was not directly assessed in this study, these findings support the safety of daily aspirin use in this population.


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