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Subcutaneous (SC) formulations of CT-P13 and vedolizumab (VED) are currently available as new treatment option for patients with inflammatory bowel disease (IBD). The decision to switch requires a shared decision making based on adequate education of the patient, to avoid negative outcomes due to a nocebo effect. The aims of this study were (1) to evaluate the percentage of patients with IBD in favour of switching to SC formulations and (2) to compare two educational strategies.

This was a multicentre study in patients with IBD on maintenance intravenous (IV) CT-P13 or VED. Patients attending the infusion unit were invited to complete a survey exploring the willingness to switch to SC formulations. In centre A, all patients were informed on the new SC formulations and the accompanying care pathway by an information leaflet and a face-to-face interaction with the IBD nurse, prior to completing the survey. In centre B, patients on a minimal interval of q8w were digital invited to the same survey via the e-health application of the hospital. Demographics, patient reported outcomes, willingness to switch and reasons for IV vs. SC preferences were captured.

In total, 447 (n=183 Centre A; n=264 Centre B; participation ratio 83.6%) patients completed the survey (m/f: 212/235; CD/UC/IBD-U: 275/161/11; median age 45 IQR 33-57; remission CD/UC: 75%/82%) see table. Most patients were open to SC treatment (47% yes, 33% doubt, 20% no). The main driver to switch was an anticipated decrease in hospital visits (86%) and overall time gain (78%). The main reason to continue IV was fear of change (60%) and uncertainty in case of relapse after switch to a SC formulation (46%). In univariate analysis, the self-estimated compliance rate was associated with the willingness to switch (p<0.0001). To evaluate the impact of the approach in patient education between the two centres, we compared the subgroup of patients on ≥q8w interval with a dosing of 5-10mg/kg CT-P13 or 300 mg VED (n=335). The willingness to switch was higher after a face-to-face approach (centre A) compared to a merely digital approach (centre B;  53.9 % vs. 40.9 % p=0.038), although patients in centre B had a higher educational level (p=0.003), more prior experience with other IBD SC medication (p=<0.001), lived further from the hospital (p<0.001) and had a younger age at diagnosis (p=0.019).

In this multicentre comparative study exploring the willingness to switch from IV to SC maintenance therapy with CT-P13 and VED, the majority is open to switch to a SC formulation. The direct approach and education of the patient by the IBD nurse impacts significantly the willingness to switch. In a follow-up we will investigate the actual switch rates.

1. To review flare management and optimisation of biologic treatments using TDM  
2. To choose an appropriate therapy for pregnant IBD patients
3. To learn how to plan peri-partum care

Educational objectives:
1. To discuss the diagnosis and management of newly diagnosed ulcerative colitis
2. To determine when and how to switch from one treatment to another to optimize management of ulcerative colitis
3. To examine anti-TNF drug and antibody levels to optimize dosing
4. To discuss preconception counseling to achieve favourable maternal and neonatal outcomes and understand the conditions under which treatments should or should not be stopped during pregnancy and lactation

Summary

We present here a case of newly diagnosed ulcerative colitis and will discuss with experts the management strategies in case of persistent disease activity, including the interest of combination therapy and therapeutic drug monitoring to guide management decision.
Preconception counseling to achieve favourable maternal and neonatal outcomes, safety of treatment during pregnancy and lactation, and management of a flare during pregnancy will also be discussed.

1. To review the therapeutic goals and patient needs in UC
2. To confer different treatment strategies in UC
3. To discuss therapeutic options in UC
4. To emphasize the advantage of tight disease control

1. To review the therapeutic goals and patient needs in UC
2. To confer different treatment strategies in UC
3. To discuss therapeutic options in UC
4. To emphasize the advantage of tight disease control

We sought out to identify proteomic markers of anti-Tumor Necrosis Factor (TNF) treatment failure in anti-TNF naive patients with Crohn's disease, using data obtained from the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study.

Background

The first line treatment for inducing remission in pediatric Crohn’s disease (CD) is Exclusive Enteral Nutrition (EEN), where a patient drinks a nutritionally complete formula exclusively for 6 to 12 weeks. Despite the effectiveness of EEN, some patients may experience challenges including taste fatigue, monotony, and a lack of social participation with meals. Given these challenges, patients may turn to popular or fad diets for managing their disease. These diets are often restrictive, eliminating a number of foods and exacerbating the risk of underlying nutrient deficiencies in this patient population.

Methods

These case studies involved a nutrient analysis of evidence-based and popular diets for CD, including Crohn’s Disease Exclusion Diet (CDED), CD-TREAT, Specific Carbohydrate Diet (SCD), IBD Anti-inflammatory Diet (IBD-AID), Autoimmune Protocol (AIP) Diet, Gut and Psychology Syndrome (GAPS) Diet, and low FODMAP. Four cases were selected with mild-moderate CD: 11-year-old and 16-year-old, both male and female. A nutrient analysis of sample menus of each diet was completed using Food Processor version of 11.6.0 by ESHA Research. Results were compared to age and gender specific Dietary Reference Intakes (DRIs), population-based dietary intake data, and Health Canada Dietary Guidelines.

Results

Data are presented for Case 1, 11-year-old male. Findings were comparable to other age and gender cases. As compared to Acceptable Macronutrient Distribution Ranges (AMDRs), there was a higher percentage of energy from fats and lower from carbohydrates for the SCD (% kcal, fat and carbohydrate respectively: 59%; 30%), IBD-AID (52%; 37%), AIP Diet (50%; 20%) and GAPS Diet (60%, 21%). Saturated fat intake exceeded recommendations (>10% of energy intake) for CDED (% kcal, 14%) CD Treat (17%), SCD (11%), AIP Diet (15%) and GAPS Diet (20%). Both vitamin D and/or calcium intake were below the Recommended Dietary Allowance (RDA) respectively for CDED (% RDA, vitamin D and calcium respectively: 89%; 86%), SCD (23%; 53%), AIP Diet (14%; 23%), low FODMAP Diet (4%, 96%) and GAPS Diet (calcium, 58%). Adolescent females versus males between the ages of 14-18 years may be at greater risk of inadequate nutrient intake, given the general increase in nutrient requirements yet lower caloric needs.

Conclusion

Given the increase in awareness and interest in popular diets for Crohn’s disease, it is imperative that clinicians are aware of the risks of inadequate nutrient intake with restrictive diets.

Upadacitinib (UPA), an oral, reversible, Janus kinase (JAK)-1 selective inhibitor can induce clinical and endoscopic remission after 8 weeks in patients (pts) with moderately to severely active Ulcerative Colitis (UC). To provide mechanistic insights into downstream effects of UPA in the intestinal mucosa, we evaluated pharmacodynamic modulation of gene expression in colon biopsies from pts with UC in the Phase 2b study, U-ACHIEVE (NCT02819635). These analyses aimed to link molecular changes to clinical endpoints. 

Transcriptomic data were collected from rectosigmoid biopsies at baseline (BL) and Week (Wk) 8 in a subset of pts in sub-study 1 of U-ACHIEVE (N=88: placebo [PBO], n=15; pooled UPA 15, 30 & 45 mg, n=73). Samples underwent bulk RNA sequencing and differentially expressed genes (DEG) (false discovery rate [FDR]<0.05 & |log fold change [FC]|>1) from BL to Wk 8 were identified with linear mixed-effect models. DEG were analysed with KEGG and GO pathway enrichment and clinical endpoint responder analysis. Cellular profiling with gut cell deconvolution based on defined cell types was undertaken.¹ 

At Wk 8, expression of 695 gut genes was modulated (FDR<0.05 & |logFC|>1) from BL after UPA treatment compared with no DEG in PBO pts (including responders). Of these genes, ~70% (n=492) were downregulated and enriched in inflammatory pathways including T- and B-cell effector responses, neutrophil-mediated immunity, and leukocyte chemotaxis. Also, irrespective of directionality, most DEG from BL to Wk 8 in UPA-treated pts were associated with clinical response and remission, and histologic and endoscopic improvement. At Wk 8, deconvoluted cell fractions associated with adaptive but also innate inflammatory cells in the gut of UPA responders were decreased compared with non-responders; in contrast, fractions associated with enterocyte, secretory goblet cell and myofibroblast cells were increased in responder gut tissue (Fig 1). Modulation of genes associated with UC disease activity (OSM & S100A8/9 [calprotectin]), Th1 (TBX21, IFNG), Th2 (GATA3, IL5RA, IL13RA2), Th9 (SPI1), Th17 (IL17A, IL23A, IL21R), B-cell responses (BTK, CD40), barrier function (ESPN, VIL1, CLDN23, OCLN, MUC1/2/12/16/20) and wound repair (ANXA1/6/13, MMP7/9) were associated with clinical improvement at Wk 8 (Fig 2).

JAK inhibition with UPA is associated with transcriptional changes in colonic mucosa that are seen with UC disease pathophysiology. Clinical benefit mediated by UPA is associated with modulation of molecular biomarkers of UC disease activity, T-helper-cell differentiation, B-cell-mediated responses, gut barrier function and wound healing.

1. Menden K, et al. Sci Adv 2020;6:eaba2619

Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH.

U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction.

Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p<0.001), RBS of 0 (p<0.05), and SFS of 0 (p<0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p<0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53-3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59-4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52-3.79) were more likely to achieve clinical remission at week 8.

UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]

Educational Objective: to review the incidence, the diagnosis, the optimisation of the patient, and the treatment of entero-urinary fistulas in Crohn’s disease.