bluuebunny/crossref_metadata_2025_split huggingface dataset:
P460 A Real-World Picture of Adverse Drug Reactions in Inflammatory Bowel Disease
Authors: Lemos Garcia J , Rosa I , Saraiva S , Moleiro J , Claro I 
Published: January 2022

Abstract

Background
Patients with Inflammatory Bowel Disease (IBD) face complications of medical treatment that may compromise their health and the drugs’ therapeutic success. Real world data regarding adverse drug reactions (ADR) is crucial.

Methods
Unicentric retrospective study. All patients followed for IBD in a tertiary Portuguese hospital between 2015–2021 were included.

Results
328 patients included-55.8% women; age at last follow-up 53.4±16.7 years old; Crohn’s Disease (CD) in 53.0%; follow-up of 15.8±10.8years. Extraintestinal manifestations(EIM) occurred in 13.1%(n=43) patients, mostly arthropathy/arthritis(n=33). Current or previous treatment included salicylates in 69.5%, thiopurines 63.1%, corticosteroids 54.3%, methotrexate 5.5%, infliximab 38.4%, adalimumab 11.6%, ustekinumab 4.9% and vedolizumab 4.6%. In total, 124 ADR occurred in 97 patients(28.7%). ADR occurred with salicylates in 20/228 patients(8.8%), corresponding to 9/215 of mesalazine and 10/26 of salazopyrin treated patients, mostly gastrointestinal(GI) intolerance(n=8). ADR occurred in 78/207(37.7%) of thiopurine-treated patients; 5 had more than one ADR to thiopurines and 10 developed ADR despite change from azathioprine to 6-mercaptopurine. Reactions included myelosuppression(n=21), GI symptoms(n=20), pancreatitis(n=8). One case of corticosteroid ADR was reported (psychosis). 4/18(22,2%) methotrexate-treated patients experienced ADR, all liver toxicity. Infliximab-associated ADR occurred in 20/126 patients(6.1%), namely infusion reactions(n=7) or lupus-like syndrome(LLS) (n=6). 9/39 adalimumab-treated patients experienced ADR, such as skin rash(n=3). No reported ADR with ustekinumab or vedolizumab. Overall, ADR led to dose adjustments in 100/120 cases and to drug suspension in 22. Nine patients needed hospital admission and one died with squamous cell carcinoma in fistula tracts. 94.9% of these ADR remitted. In the univariate analysis, ADR were associated with IBD type(p=0.040), EIM(p=0.001), UC extent(p=0.016), thiopurine(p&lt;0.001), infliximab(p&lt;0.001) and adalimumab (p=0.005) exposure. In multivariate analysis, significance was kept with EIM(p=0.003), thioupurine(p=0.006) and infliximab(p=0.003) exposure. Patients who had one ADR, were not more likely to have ADR with other drugs.

Conclusion
ADR occurred in 28.7% of IBD patients and the most commonly implicated drugs were salazopyrin (10/26, 38.5% of patients) and thiopurines (75/207, 36.2%), rates much higher than those found with mesalazine and biologics. Nevertheless, most of these reactions resolved with dose adjustments or drug suspension, without hospital admission. This indicates that drugs available for IBD treatment remain safe, but their use must be cautious and toxicities should be monitored.
P464 Rac1/pSTAT3 expression in T lymphocytes: A potential pharmacodynamic marker for thiopurines in the treatment of Inflammatory Bowel Disease patients?
Authors: Deben D , Creemers R , Van Adrichem A , Drent R , Merry A , Leers M , Van Bodegraven A , Wong D 
Published: January 2022

Abstract

Background
The thiopurine derivatives, azathioprine (AZA), mercaptopurine (MP) and tioguanine (TG), remain standard treatment of Inflammatory Bowel Diseases (IBD). To date, therapeutic drug monitoring (TDM) is used to optimize thiopurine therapy. However, since this provides mainly pharmacokinetic information, TDM is of limited use to predict clinical effectiveness or to explain therapeutic failure. A specific pharmacodynamic marker would therefore be of more beneficial use. The immune suppressive mechanism of thiopurines, by the active thiopurine metabolite 6-thioguanine triphosphate, is primarily based on blocking the Ras-related C3 botulinum toxin substrate 1 (Rac1) causing T-cell apoptosis by inhibition of the phosphorylated downstream transcription factor signal transducer and activator of transcription 3 (pSTAT3) (Figure 1). The aim of this study was to explore whether expression of Rac1 and pSTAT3 in T-cells may be used as a pharmacodynamic marker for the therapeutic effect of thiopurine therapy in IBD patients.

Methods
To assess feasibility, T-cell Rac1 and pSTAT3 expression was evaluated in six parallel IBD groups: patients with active disease (1) and patients in remission on AZA/MP (2), TG (3), infliximab (IFX) (4), thiopurine and IFX (5) or without medication (6). Data of healthy subjects were used as reference values. Rac1 and pSTAT3 expression of patients in remission on AZA/MP or TG were compared to all other IBD groups and healthy subjects.

Results
Absolute Rac1 expression in T-cells did not differ between any of the IBD patient groups (Figure 2). A decrease in absolute pSTAT3 expression was found in IBD patients in remission on AZA/MP or TG, when compared to active disease patients, although not statistically significant. Notably, Rac1-corrected pSTAT3 expression was decreased in IBD patients in remission on AZA/MP or TG compared to active disease patients (p&lt;0.01). This effect was not observed in the IBD groups in remission on other immunosuppressive therapy.

Conclusion
Rac1-corrected pSTAT3 expression in T-cells was significantly decreased in IBD patients in remission on thiopurine monotherapy compared to IBD patients with active disease, resulting in comparable values to healthy subjects. Rac1/pSTAT3 expression may serve as a potential, class specific pharmacodynamic marker to assess therapeutic efficacy of thiopurine monotherapy or as a marker to explain thiopurine resistance.
P471 Real-world experience of using Tofacitinib in Ulcerative Colitis in biologic naïve and biologic exposed patients
Authors: Cheesbrough J , Quraishi M N , Sharma N , Nassar I 
Published: January 2022

Abstract

Background
Tofacitinib is an oral, small molecule, which recently received NICE approval for the treatment of moderate to severe treatment refractory ulcerative colitis (UC). We present data on the regional experience for it use in relation to its efficacy in a cohort of patients with UC.

Methods
This study analysed a retrospective, cohort from a large IBD unit in the UK. Patients with UC commenced on tofacitinib between 2019 and 2021 for active disease were included. Clinical disease activity was assessed at baseline, week 8, week 16 and during follow up visits. We evaluated clinical response (&gt;50% reduction in symptoms) at week 8, proportion of patients requiring extended of induction therapy to week 16 and need for re-escalation of maintenance dosing.

Results
A total of 55 patients were included (median age 34 years; IQR 15.75). Twenty six (47.3%) patients had pancolitis, 20 (36.4%) were biologic naïve and 18 (32.7%) were exposed to more than one biologic. Eighteen patients (32.7%) entered clinical response at week 8 and were able to de-escalate to 5mg BD maintenance therapy. Six patients (10.9%) had a primary non response and required a switch to an alternative biologic or a colectomy. Of the patients given an extended induction period (10mg BD for 16 weeks), 7/31 (22.6%) were able to de-escalate to 5mg BD, 15/31 (48.4%) continued on 10mg BD as maintenance and 9/31 (29.0%) discontinued treatment due to lack of clinical response. Of the patients on 5mg BD as maintenance 10/24 (41.6%) required re-escalation to 10mg BD maintenance dosing following a median duration of 10 weeks. Primary non response to tofacitinib were similar in biologic naïve patients compared to biologic exposed patients (25% vs 28.5% respectively). Biologic exposed patients were more likely to need 10mg BD as maintenance dosing compared to biologic naïve patients (72% vs 46.7% respectively).

Conclusion
Consistent with prior literature, our experience confirms the effectiveness of Tofacitinib in both biologic naive and biologic exposed patients with moderate to severe UC with similar clinical response between the two cohorts. Patients exposed to biologics however appear to have a greater likelihood of escalation to 10mg BD for maintenance therapy.
P475 Profiling the use of Complementary Alternative Medicines among IBD patients
Authors: Sudhakar P , Stiers R , Dycker E D , Geens P , Paps A , Lambrechts T , Keersmaekers B , Sabino J , Ferrante M , Vermeire S , Verstockt B 
Published: January 2022

Abstract

Background
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease of the gut, characterized by multiple symptoms of which some cannot be successfully managed by existing conventional therapies. The use of complementary alternative medicines (CAMs) and CAM services among patients with chronic disorders including IBD has increased globally over the past several years (Rawsthorne Gut 2012; Weizman APT 2012). The main aims of this study were (a) to profile the use of CAMs and CAM services in a cohort of IBD patients being treated at a Belgian IBD referral center and (b) to identify the clinical and demographic factors associated with the use of CAMs.

Methods
An anonymized and customized Dutch version of the international questionnaire to measure the use of complementary and alternative medicine (I-CAM-Q – Quandt J Altern Complement Med 2009) was provided over an 8-week period spanning September and October 2021) to all IBD patients visiting the IBD outpatient clinic and infusion unit. Pearson’s Chi-square test was used to identify the relationships between clinical and demographic variables (age, gender, educational status) and CAM usage.

Results
From among the 410 IBD (144 UC, 253 CD) patients who responded to the survey, 173 (42.2%) were using CAMs or had used CAMs. A vast majority (79.8%) of the CAM using IBD patients reported the use of nature-based therapies (aloe vera, green tea, curcumin, cannabis, vitamin/mineral supplements and probiotics), a fifth of which was accounted for by Cannabis and its derivatives. This was followed by mind-body therapies (42.1%) (mindfulness, yoga, acupuncture, hypnotherapy, meditation). Two-thirds of patients (66.7%) mentioned to use CAMs for IBD-related symptoms. 125/173 of the CAM using IBD patients attributed the use of CAMs to their know-how about the potential of CAMs in ameliorating symptoms (32%), low efficacy or presence of adverse effects of conventional therapies (29.6%), minimize disease burden (28.8%) and avoiding surgery (7.2%). A vast majority (93.9%) of the CAM using IBD patients who responded to the query stated that consultation with their gastroenterologist would be beneficial to ascertain possible interference with their ongoing conventional therapy.

Conclusion
A significant proportion of IBD patients use CAMs to manage the complicated and often systemic symptoms of IBD. The most frequently used CAMs included nature-based therapies such followed by mind-body medicine. Given that CAMs are not officially regulated as medicinal therapies, their impact on conventional therapies is not entirely clear and should be further studied. Multi-center surveys profiling the use of CAMs in IBD patients as well as other chronic disorders are warranted.
P485 Apolipoprotein C3 is Downregulated in Patients with Inflammatory Bowel Disease
Authors: Hernandez Camba A , Carrillo Palau M , Ramos L , Alonso I , Vela M , Hernández A , Arranz L , Hernández N , Hernández-Guerra M , Ferráz I 
Published: January 2022

Abstract

Background
Inflammatory bowel disease (IBD) has been associated with an abnormal lipid profile. Apolipoprotein C3 (ApoC3) is a key molecule of triglycerides metabolism that is known to be related to inflammation and cardiovascular (CV) disease. In the present study, we aim to study if ApoC3 serum levels differ between patients with IBD and controls, and if the hypothetical disturbance of ApoC3 can be explained by IBD characteristics.

Methods
Cross-sectional study that included 405 individuals, 197 patients with IBD and 208 age- and sex-matched controls. ApoC3 and standard lipid profiles were assessed in patients and controls. A multivariable analysis was performed to analyze whether ApoC3 serum levels were altered in IBD and to study their relationship to IBD characteristics.

Results
After fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with IBD showed significant lower serum levels of ApoC3 (beta coef. -1.6 [95%CI -2.5- -0.7] mg/dl, p=0.001). Despite this, inflammatory markers, disease phenotypes or disease activity of IBD were not found to be responsible for this downregulation.

Conclusion
Apolipoprotein C3 is downregulated in patients with IBD.
P500 The use of budesonide results in lower risk for infections compared to systemic glucocorticoids
Authors: Pallmer K , Timeus S , Laoun R 
Published: January 2022

Abstract

Background
We analysed the occurrence of infections with individuals treated with either budenoside (locally acting) or systemically available glucocorticoids (GC); prednisolone, prednisone and methylprednisolone. The risk of infection was divided according to the origin; viruses, bacteria, fungi and parasites and we assessed which virus and bacterium caused the most side-effects between locally and systemically acting GC.

Methods
In this analysis, infection reported outcomes with GC drugs reported to FAERS (USA) were extracted and compared to approximately 25’000 drugs in the database. Odds ratio (OR) and 95% confidence interval (CI) for the association of infections between budesonide and systemic GC. The data were classified into virus, bacteria, fungi, parasites and non-defined infections. The number of reported side-effects were ranked from highest to lowest, the 20 most reported viral and bacterial infection were assessed, respectively. All related terms for one species were combined e.g. “SARS-CoV-2” and “Coronavirus”.

Results
The database contained 20’363 reports for budesonide, 35’452 for methylprednisolone, 60’516 for prednisolone and 102’982 for prednisone. Of these, a total of 4’465 concerned infection related AEs associated with the budesonide and 93’020 for systemic steroids. Bacteria and virus associated side-effects seemed to be more pronounced with the use of systemic GCs, while for fungal infections the risk was less prominent. Interestingly, budesonide users reported less parasite infections compared to systemically GC treated patients (Fig. 1). The highest number of infections of viruses and bacteria were analysed (generic terms such as “Viral infection” were excluded).The most frequent reported viral infections were Herpes Viruses followed by Influenza, Hepatitis B Virus and SARS-CoV-2. Budesonide treated individuals have a lower risk for virus infections, except for influenza, Adenovirus and Respiratory Synctial Virus (Fig. 2); there was a reduced risk for all bacterial infections in budesonide treated patients, compared to systemic GC. The most reported bacterial infections were Mycobacterium Tuberculosis, Escheria Coli and Clostridium Difficile (Fig. 3).

Conclusion
This unbiased analysis revealed that the use of budesonide was associated with a lower risk of infections of viruses, bacteria and parasites compared to systemic GC. In order to reduce the risk of infections, especially during the COVID-19 pandemic, inflammatory bowel disease patients should, where possible, switch from systemic GC to budesonide.
P504 Prospective analysis of micronutrient status and disease course in Inflammatory Bowel Disease
Authors: Brownson E , Saunders J , Gerasimidis K , Karafoulidou Z , Seenan J P , Macdonald J 
Published: January 2022

Abstract

Background
Biochemical deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium and zinc are common in patients with Inflammatory Bowel Disease (IBD) and some micronutrient deficiencies have been associated with adverse disease outcomes. This study describes the micronutrient status of a cohort of patients on biologic therapy for IBD and explores the relationship with disease activity.

Methods
Adult patients with IBD on biologic therapy attending the nurse specialist clinic had 16 serum micronutrients measured alongside routine biochemical screening for disease activity. 12 months of follow up data was collected using electronic patient records. Faecal calprotectin (FCP), albumin and CRP were measured at baseline - patients in whom these biomarkers were within normal range (i.e CRP &lt;10mg/L, albumin &gt;35g/L and FCP &lt;250µg/g) were defined as being in biochemical remission. Disease relapse at follow-up was defined as escalation of maintenance therapy, use of corticosteroid, hospital admission or surgery.
Relationships between micronutrient status and time to disease relapse were explored.

Results
216 patients (42% female, median age 42, IQR: 30–57) were included. 128 patients had Crohn’s disease (CD). 97 patients were in biochemical remission at enrolment.
12.9% of the total cohort were zinc (Zn) deficient and 6.5% were selenium (Se) deficient. Deficiencies of folate, vitamin C, vitamin B12, vitamin B6 and vitamin D were also prevalent within the cohort.
Se deficiency was associated with high CRP (p=.001), low albumin (p=.022), and raised FCP (p=.002) at baseline. Zn deficiency was associated with high CRP (p&lt;.001) and low albumin (p&lt;.001). During the 12 month follow up period, 22/216 patients suffered a disease relapse.
Patients with low Zn or low Se levels at baseline were significantly more likely to relapse (p=.007 and p=.019 respectively). In subtype analysis, patients with CD and Zn deficiency were significantly more likely to relapse (p=.003) but this was not the case for UC patients. Patients with UC and Se deficiency were significantly more likely to relapse (p=.001) whereas those with CD were not.

Conclusion
Zn and Se biochemical deficiencies are common in our cohort of IBD patients on biologic therapy and are predictive of subsequent disease relapse. Whether these signals are causal or a secondary effect of disease activity needs to be explored in future intervention studies.
P508 The impact of disease duration and early biologic treatment on transmural healing in Crohn’s disease
Authors: Revés J , Freire G , Sousa P , Primitivo A , Nascimento C , Morão B , Abreu N , Palmela C , Glória L , Torres J 
Published: January 2022

Abstract

Background
Although transmural healing (TH) has not yet been considered a formal target in CD, it is considered a desired goal, as it seems to be associated with better outcomes. Early biologic treatment has been shown to lead to higher clinical remission and increased endoscopic healing. However, to date, there is no information on the impact of disease duration on TH. We aimed to assess the efficacy of early biologic treatment on the achievement of TH.

Methods
Unicentre retrospective cohort study comparing patients who started early and late biologic therapy (defined as ≤ 12 months vs &gt; 12 months from diagnosis). We included patients with CD who were receiving biologic therapy, and had a baseline computed tomography enterography (CTE) or magnetic resonance enterography (MRE) before the initiation of a biologic (median 2.5, IQR 0–50 months), and a follow-up CTE/MRE performed 12 ± 6 months after therapy initiation. Endoscopic healing was defined as a SES-CD score &lt;3. Three experienced radiologists blinded to the therapeutic group reviewed every CTE and MRE and assessed several pre-defined parameters of cross-sectional inflammation. TH was defined as the absence of active inflammation, extra-enteric signs, and CD-related complications (strictures, fistulas or abscesses). The effect of early biologic treatment on transmural healing was analysed using logistic regression.

Results
60 patients were included (51.7% males), with a median age at diagnosis of 24.5 years old (IQR 17.5–32.5). Most patients had ileocolonic disease (58.3%) and non-stricturing non-penetrating phenotype (60%). Twenty-eight patients (46.7%) started biologic therapy within the first 12 months of diagnosis. There were no significant differences in baseline clinical features or baseline radiologic assessment between the groups, except for the extension of the most affected segment, which was higher in the group of late biologic therapy (197 vs 129.5mm, p=0.05) (Table 1). Patients on early biologic treatment achieved endoscopic healing more frequently than those on late biologic treatment (65.4% vs 23.3%, p=0.002). Early biologic treatment was also associated with increased transmural healing (OR 4.1, 95% CI 1.2–13.6, p=0.02). In a multivariate model including baseline characteristics of the disease, only the use of biologics within the first 12 months and the absence of ileocolonic disease were significant predictors of the achievement of transmural healing (Figure 1).

Conclusion
Early biologic treatment seems to be independently associated with higher transmural healing rates, further adding to the relevance of early intervention in CD. Our findings are limited by the small sample size and short follow-up.
P522 Upadacitinib Promotes Histologic and Endoscopic Mucosal Healing: Results from the Upadacitinib Ulcerative Colitis Phase 3 Program
Authors: Peyrin-Biroulet L , Siegel C , Tanida S , Bossuyt P , Torres E , Dubinsky M , Baert F , Zhou W , Klaff J , Berg S , Laroux F S , Sanchez Gonzalez Y , Yao X , Zhou Q , Reinisch W 
Published: January 2022

Abstract

Background
Upadacitinib (UPA), an oral selective and reversible JAK inhibitor, demonstrated significantly greater efficacy compared to placebo (PBO) as treatment for moderate to severe ulcerative colitis (UC), in phase 3 induction (U-ACHIEVE and U-ACCOMPLISH) and maintenance (U-ACHIEVE Maintenance) studies. We evaluated UPA efficacy on histologic outcomes with or without endoscopy in this phase 3 program. The STRIDE II initiative identified histological healing as a treatment target signaling the importance of histologic endpoint inclusion in clinical trials and practice.

Methods
The UC phase 3 program were multicenter, double-blind PBO-controlled trials. Induction studies enrolled adult patients with moderate to severe active UC (defined as Adapted Mayo Score of 5–9 points and a centrally reviewed endoscopy subscore of 2–3), with randomization 2:1, UPA 45mg (UPA45) once daily (QD) or PBO. Patients eligible for U-ACHIEVE Maintenance primary analysis (N=451) were clinical responders (per Adapted Mayo score) to 8-weeks (wks) of induction treatment with UPA45. U-ACHIEVE Maintenance patients were randomized 1:1:1 UPA 15mg QD (UPA15): UPA 30mg QD (UPA30): PBO for 52 wks. Endpoints were assessed at wk 8 and/or 52: histological improvement, histologic remission, histologic endoscopic mucosal improvement (HEMI), and mucosal healing (a more stringent endpoint defined as endoscopic score=0 and Geboes score&lt;2.0). For endpoint definitions, see Tables 1 and 2.

Results
Baseline characteristics were similar at wk 0 of induction or maintenance studies. In U-ACHIEVE Induction, patients treated with UPA45 demonstrated a significant increase in histologic improvement (55.0% vs 22.5%), HEMI (30.0% vs 6.6%), and mucosal healing (10.7% vs 1.3%); compared to PBO-treated patients (p&lt; 0.001 for all endpoints, Table1). In U-ACCOMPLISH, patients treated with UPA45 experienced superior efficacy in histologic improvement (62.2% vs 24.5%), HEMI (36.7% vs 5.8%), and mucosal healing (13.5% vs 1.7%) compared to PBO-treated patients (p&lt;0.001 for all endpoints). Significantly higher percentages of patients that received UPA15 and UPA30 (42.8% and 56.9%) at wk 52 demonstrated increased histological improvement compared to PBO-treated patients (20.6%; p&lt;0.001). In addition, patients treated with UPA15 and UPA30 demonstrated superior HEMI (UPA15 34.8%; UPA30 49.3%; PBO 11.8%, p&lt;0.001) and mucosal healing rates (UPA15 17.6%; UPA30 19.0%; PBO 4.7%; p&lt;0.001 for both endpoints).

Conclusion
UPA induction and maintenance treatment achieved superior efficacy compared to PBO for all histologic and endoscopic assessments including mucosal healing. [Clinicaltrials.gov, U-ACHIEVE Induction and Maintenance (NCT02819635) and U-ACCOMPLISH (NCT03653026)]