scholarly journals P847 A pilot trial on the effect of a fibre-enriched nutritional supplement on the gut microbiota of stricturing Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S653-S653
Author(s):  
C M Herrera De Guise ◽  
E Varela ◽  
A Ibarz ◽  
R Burgos ◽  
G Cardenas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Pilot Trial ◽  
Nutritional Supplement ◽  
Ileocecal Resection ◽  
Faecal Calprotectin ◽  
Soluble Fibre ◽  
Low Residue Diet

Abstract Background Diet is a potential factor that could influence the pathogenesis and activity of Inflammatory Bowel Disease(IBD). Soluble fibre is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Around 1/3 of Crohn’s disease (CD) patients will present with stricturing disease, most frequently in the terminal ileum. These patients often follow a very low-residue diet. CD patients present significant changes in the structure of their microbiota with a decreased prevalence of butyrate-producing bacteria such as Clostridiales species, particularly Faecalibacterium prausnitzii. Depletion of F. prausnitzii might be further enhanced in patients with a very low-residue diet. The aim of this study was to evaluate the effect of a nutritional supplement enriched with soluble fibre on the abundance of F. prausnitzii in stricturing CD. Methods We performed a single arm, pilot trial in CD patients with ileal stricturing disease who followed a very low-residue diet as assessed by a dietician. The fibre-enriched nutritional supplement (reg#26.06141/BA-72556) consisted of a 200ml vanilla-flavoured shake that included 3.4 gr of soluble fibre, omega-3 and oleic fatty acids. Patients received 2 supplements per day for 6 weeks, and were followed for 6 months. We obtained frozen faecal samples at time-points 0, 3, 6, 12 and 24 weeks. Total bacteria and F. prausnitzii counts were assessed by qPCR. Weight, BMI, CD activity index (CDAI), CRP, fatty acids, urine F2-isoprostanes and faecal calprotectin were also determined. Tolerance, palatability and acceptability of the supplement were assessed with validated questionnaires at weeks 3 and 6. Results Ten patients were included in the study with a median age of 38 [36–50] years, 60% were male, median BMI 25.2 [24.3–28.4] and 40% were current smokers. Six patients completed the 6 weeks of the supplement. Two patients did not receive the supplement because they underwent ileocecal resection, 1 patient was lost to follow-up and 1 patient dropped-out early because of poor palatability of the supplement. At baseline, all patients had F. prausnitzii levels below 109 CFU/g (median 2.02 × 106). Supplement intake did not significantly increase F. prausnitzii levels (p = 0.73) and had no effect on CDAI, CRP, urine F2-isoprostanes or faecal calprotectin. Most usual complaints associated with the supplement were abdominal bloating and flatulence. Conclusion CD patients with structuring disease and who follow a very low-residue diet have a markedly reduced abundance of F. prausnitzii. Intake of a 6.8 g/day fibre-enriched nutritional supplement was unable to significantly increase F. prausnitzii abundance in these patients. Fibre supplement was not associated with adverse events.

DOP71 Efficacy, safety, and tolerability of ustekinumab in paediatric patients with moderately to severely active Crohn’s disease: Results from, UniStar, a phase 1 study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
J Rosh ◽  
D Turner ◽  
A Griffiths ◽  
D Jacobstein ◽  
O Adedokun ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Opportunistic Infections ◽  
Activity Index ◽  
Phase 1 ◽  
Double Blind ◽  
Faecal Calprotectin ◽  
Adequate Treatment ◽  
Safety And Efficacy ◽  
Paediatric Patients

Abstract Background Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD). The objective of this study was to evaluate the pharmacokinetics (PK), safety, and efficacy of UST in paediatric patients with moderately to severely active CD who had failed treatment with corticosteroids (CS) and/or immunomodulators (IM) and/or anti-tumour necrosis factor (TNF) therapies. Here, we report the safety and efficacy results through Week 16; PK results are reported separately. Methods This was a Phase 1, multicentre, 16-week, double-blind induction dose-ranging study (NCT02968108) in patients aged 2 to <18 years (body weight [BW] ≥10 kg) with a Paediatric CD Activity Index (PCDAI) score >30 and at least an abnormal C-reactive protein >3.0 mg/l or faecal calprotectin >250 µg/g), or ulcerations in the ileum or colon upon ileocolonoscopy despite adequate treatment with CS ± IM ± anti-TNF therapy. Patients were randomised (1:1) and stratified by weight and prior anti-TNF use for induction to one of 2 weight range-based intravenous (IV) doses: 130mg vs. 390 mg if BW ≥40 kg and 3 mg/kg vs. 9 mg/kg if BW <40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW <40 kg. Results Forty-four patients (59% ≥40kg BW; >90% anti-TNF exposed) were randomised (n = 23 lower dose; n = 21 higher dose) and treated with UST. Baseline characteristics are summarised in Table 1. At week 16, in the lower dose and higher dose groups, 52%/52% achieved clinical response (reduction in PCDAI ≥15) and 22%/29% had clinical remission (PCDAI ≤10), respectively (Table 2). In addition, 32% and 28% of patients showed endoscopic response (reduction in Simple Endoscopic Score for CD of ≥50%), respectively. Through week 16, 73% of patients reported ≥1 adverse event (AE; 82.6% lower dose vs. 62% higher dose); 2 discontinued due to AEs (1 in each group). Serious AEs occurred in 16% of patients (26% lower dose and 5% higher dose, with CD exacerbation being the most frequent (13%/5%, respectively). Infections occurred in 41% of patients (1 was serious, which was intestinal abscess that spontaneously resolved with sequelae). No injection site reactions, opportunistic infections, malignancies, or deaths were reported. No antibodies to UST were observed. Conclusion As early as 3 weeks and through 16 weeks, both the lower and higher doses of UST (IV week 0 and SC at week 8) improved clinical and endoscopic disease activity in this previously treatment-refractory group of children with CD. The safety profile was consistent with that for UST in adults with CD.

Azithromycin and metronidazole versus metronidazole-based therapy for the induction of remission in mild to moderate paediatric Crohn’s disease : a randomised controlled trial

Gut ◽  
2018 ◽  
Vol 68 (2) ◽  
pp. 239-247 ◽  
Author(s):  
Arie Levine ◽  
Michal Kori ◽  
Jarek Kierkus ◽  
Rotem Sigall Boneh ◽  
Malgorzata Sladek ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Randomised Controlled Trial ◽  
Crohn's Disease ◽  
Activity Index ◽  
Controlled Trial ◽  
Open Label ◽  
Faecal Calprotectin ◽  
Group 2 ◽  
Randomised Controlled ◽  
Group 1

ObjectiveCrohn’s disease (CD) pathogenesis associated with dysbiosis and presence of pathobionts in the lumen, intracellular compartments and epithelial biofilms. Azithromycin is active in all three compartments. Our goal was to evaluate if azithromycin-based therapy can improve response and induce remission compared with metronidazole alone in paediatric CD.DesignThis blinded randomised controlled trial allocated children 5–18 years with 10<Pediatric Crohn’s Disease Activity Index (PCDAI)≤40 to azithromycin 7.5 mg/kg, 5 days/week for 4 weeks and 3 days/week for another 4 weeks with metronidazole 20 mg/kg/day (group 1) or metronidazole alone (group 2), daily for 8 weeks. Failures from group 2 were offered azithromycin as open label. The primary end point was response defined by a decrease in PCDAI>12.5 or remission using intention to treat analysis.Results73 patients (mean age 13.8±3.1 years) were enrolled, 35 to group 1 and 38 to group 2. Response and remission rates at week 8 were identical 23/35 (66%) in group 1 and 17/38 (45%) and 15/38 (39%) in group 2 (P=0.07 and P=0.025, respectively). The needed to treat for remission was 3.7. Faecal calprotectin declined significantly in group 1 (P=0.003) but not in group 2 (p=0.33), and was lower at week 8 (P=0.052). Additional therapy was required in 6/35(17%) from group 1 versus 16/38(42%) in group 2 (P=0.027) by week 8. Among 12 failures in group 2, open-label azithromycin led to remission in 10/12 (83%).ConclusionsThe combination of azithromycin and metronidazole failed to improve response but was superior for induction of remission and reduction in calprotectin.Trial registration numberNCT01596894.

scholarly journals Golimumab in adolescents with Crohn’s disease refractory to previous tumor necrosis factor antibody

2020 ◽  
Author(s):  
Judith Pichler ◽  
Nima Memaran ◽  
Wolf-Dietrich Huber ◽  
Christoph Aufricht ◽  
Bettina Bidmon-Fliegenschnee
Keyword(s):  
Crohn’S Disease ◽  
Tumor Necrosis Factor ◽  
Crohn's Disease ◽  
Tumor Necrosis ◽  
Activity Index ◽  
Rescue Therapy ◽  
Disease Activity Index ◽  
Full Blood Count ◽  
Faecal Calprotectin ◽  
Necrosis Factor

Abstract Background Inducing and maintaining clinical remission in children with Crohn’s disease (CD) is associated with treatment with antibody to tumor necrosis factor (TNF)-α such as infliximab or adalimumab. In the treatment of paediatric CD, there are no data about the use of a third introduced subcutaneous TNF-antibody, golimumab, Methods We evaluated the efficacy of golimumab for adolescents with moderate/severe CD. Retrospective analyses were done in all 7 (5 girls) adolescents who received golimumab at a median age of 17 years for a median of 7.2 months. Paediatric Crohn’s disease activity index (PCDAI), full blood count, inflammatory markers, use of corticosteroids and adverse events were recorded. Results With golimumab, 5 of the 7 children were PCDAI responders and 2 entered remission (PCDAI<10). There was a significant increase in haematocrit after 2 weeks, faecal calprotectin was significantly reduced after 4 weeks compared to baseline. Out of five children, steroid withdrawal was possible in one and steroid reduction in two cases. There were no serious side effects. Conclusion With moderate/severe CD, golimumab induced and maintained clinical response. The majority of children were PCDAI responders, in most steroid sparing was possible. Golimumab might be an effective rescue therapy in refractory CD.

scholarly journals P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S318-S319
Author(s):  
C Lansdorp ◽  
K Gecse ◽  
C Buskens ◽  
M Löwenberg ◽  
J Stoker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Hyperbaric Oxygen ◽  
Activity Index ◽  
Perianal Disease ◽  
Faecal Calprotectin ◽  
Preliminary Results ◽  
Patient Reported

Abstract Background Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results. Methods 17 patients with pCD refractory to conventional-therapy &gt; 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO. Results 17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p &lt; 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment. Conclusion Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.

scholarly journals DOP13 Clinical and endoscopic response to ustekinumab in Crohn’s disease: Week 16 interim analysis of the STARDUST trial

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S049-S052 ◽  
Author(s):  
S Danese ◽  
S Vermeire ◽  
G D’Haens ◽  
J Panés ◽  
A Dignass ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Activity Index ◽  
Standard Of Care ◽  
Treat To Target ◽  
Faecal Calprotectin ◽  
Intention To Treat

Abstract Background Treat-to-target (T2T) strategy may optimise IBD disease management. We describe interim clinical and endoscopic results of the STARDUST trial in Crohn’s disease (CD) patients, following 16 weeks (W) of ustekinumab (UST) induction. Methods STARDUST, an ongoing phase 3b randomised strategy trial, enrolled adults with moderate–severely active CD (CD activity index [CDAI] 220–450) and simple endoscopic index for CD [SES-CD] ≥3) who failed conventional therapy ±1 biologic. At W0, patients received intravenous, weight-based UST of ~6mg/kg (approved label) and at W8, subcutaneous UST 90mg. At W16, patients with CDAI reduction ≥70 points were randomised (1:1) to T2T or standard of care. Key endpoints (intention-to-treat [ITT] set, as observed) were analysed at W8 and W16: % patients in clinical remission (CDAI score &lt;150); % patients with a clinical response (CDAI &lt;150 or decrease vs. baseline [BL] ≥100 points); faecal calprotectin (FCal) and C-reactive protein (CRP) levels: normalisation of FCal or/and CRP; improvement ≥50% vs. BL (patients with elevated FCal and CRP subpopulations); change vs. BL in CDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) total scores. Patients randomised to T2T underwent colonoscopy at W16 and were analysed for change in SES-CD score vs. BL, endoscopic response (decrease in SES-CD score ≥50% vs. BL) and endoscopic remission (SES-CD score ≤2) (central reading). Results The ITT full set included 500 patients with BL mean (SD) CDAI score 282.3 (65.8), SES-CD 13.1 (8.1), CRP 15.7 (23.4) mg/l, FCal 1741.9 (2932.1) mg/g and disease duration 9.4 (8.7) years; 58.4% previously failed 1 biologic. At W16, 79.4% of patients had a clinical response and 66.6% were in clinical remission. About half of the patients showed ≥50% improvement in FCal and CRP levels, which normalised in about 1/3 of patients. Results were similar irrespective of previous biologic (Table 1); 84% of patients in response at W16 were in clinical remission. Statistically significant changes from BL in CDAI, FCal, and CRP were observed at W8, and in IBDQ scores at W16 (Table 2). In the T2T set (n = 220; CDAI 70 responders), BL characteristics were similar to the full analysis set; SES-CD score was 13.4 (8.8). At W16, 36.8% and 11.4% of patients in the T2T set achieved endoscopic response and remission, respectively. The endoscopic response was independent of BL SES-CD score and disease duration, but numerically better for colonic vs. ileal disease. No new safety signals were reported. Conclusion STARDUST is the first T2T trial in CD patients. After 16 W following induction with UST, 2/3 of patients achieved clinical remission. Thirty-seven per cent of those randomised to the T2T arm (CDAI 70 responders) showed endoscopic response by central reading at W16. Results were similar irrespective of being bio-naïve or failing 1 biologic.

scholarly journals DOP14 Modelling of the relationship between infliximab exposure, faecal calprotectin, and endoscopic remission in patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S052-S053 ◽  
Author(s):  
E Dreesen ◽  
S Berends ◽  
D Laharie ◽  
G D’Haens ◽  
S Vermeire ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Simulated Patients ◽  
Dose Escalation Study ◽  
Faecal Calprotectin ◽  
Indirect Response ◽  
Flat Dose ◽  
Biomarker Response ◽  
Endoscopic Remission

Abstract Background Less than 50% of patients with Crohn’s disease (CD) starting infliximab (IFX) therapy achieve endoscopic remission (ER). Evidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the IFX dose-exposure-biomarker-response (faecal calprotectin [fCal] and ER) relationship in patients with CD. Methods Analyses were performed using data of a phase 4 dose-escalation study (TAILORIX). Patients started standard 5 mg/kg IFX induction therapy at weeks [w]0, 2 and 6. From w14 through w54, the IFX dose could be irreversibly doubled based on one of the three monitoring algorithms.1 Endoscopies were performed at w0, 12 and 54. Three sequential models were developed: A 2-compartment popPK model linking IFX dose to exposure, an indirect response popPK-PD model describing the inhibitory effect of IFX exposure on fCal, and a first-order Markov popPD model linking fCal to transitions between states of ER (CD endoscopic index of severity &lt;3), no ER and dropout (Figure 1). All modelling and simulation were performed using NONMEM 7.4. Results The study included 116/122 (95%) patients with CD enrolled in TAILORIX who had ≥1 detectable IFX serum concentration. In the developed models, it was shown that IFX clearance increased with increasing fCal, decreasing albumin, increasing CD activity index and presence of antibodies to IFX (transiently). Baseline fCal increased with increasing CRP and decreasing platelet count. Lower fCal increased probability of attaining ER and decreased probability of losing ER. Probability of dropping out given an earlier state of absence of ER increased with elapsing time. Simulations of 150 000 patients receiving 5, 7.5 or 10 mg/kg IFX (1:1:1) resulted in a flat dose–response curve due to large interindividual variability in PK and PD (Figure 2, top panels). The predicted fraction of patients achieving ER at w12 was 45.1% [30.3–60.5] (median [IQR]) when on 5 mg/kg IFX (~46.4% observed in data). However, simulations of 10 mg/kg IFX induction doses predicted only a slight increase in the fraction of patients achieving ER at w12 to 47.5% [32.0–62.6]. This minor benefit at the population level argues against systematic 10 mg/kg induction dosing in all patients. A similar observation was done during maintenance therapy, where 70.8% [62.6–75.5] of all simulated patients maintained ER at w54 (~72.2% observed in data) (Figure 2, right panels). Conclusion Model-informed infliximab dose optimisation towards a predefined fCal concentration—while accounting for PK and PD variability—may improve the effectiveness of infliximab therapy (eg. 64% chance of ER at w12 ~100 μg/g fCal at w6). Reference

scholarly journals The Assessment of Plasma Fatty Acid Profiles in Newly Diagnosed Treatment-Naïve Paediatric Crohn’s Disease

2021 ◽  
pp. 799-808
Author(s):  
J SCHWARZ ◽  
M VECKA ◽  
F STOŽICKÝ ◽  
R POMAHAČOVÁ ◽  
B STAŇKOVÁ ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Fatty Acid ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Methyl Esters ◽  
Newly Diagnosed ◽  
Treatment Naïve

Fatty acid (FA) profiles as potentially relevant components of Crohn’s disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn’s Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naïve newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

scholarly journals P655 Pharmacokinetics of ustekinumab in children and adolescents with moderately to severely active Crohn’s disease: Results from UniStar, a phase 1 study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S539-S540
Author(s):  
O Adedokun ◽  
J Hyams ◽  
D Turner ◽  
A Griffiths ◽  
N Terry ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dose Group ◽  
Activity Index ◽  
Phase 1 ◽  
Double Blind Study ◽  
Double Blind ◽  
Faecal Calprotectin ◽  
Adequate Treatment ◽  
The Impact

Abstract Background Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD) or ulcerative colitis. In the UniStar study, the pharmacokinetics (PK) of UST and its relationship with efficacy was evaluated in children who failed prior therapy. UniStar consisted of a PK portion (week 0–16) and extension (week 16–216); we report data through week 16. Methods UniStar is a multicentre, double-blind study (NCT02968108) designed to assess the PK, safety, and efficacy of UST in children (2–&lt;18 years) with moderately to severely active CD, Paediatric CD Activity Index (PCDAI) score &gt;30, and evidence of inflammation as measured by C-reactive protein &gt;3.0 mg/l or faecal calprotectin &gt;250 µg/g or ulcerations on ileocolonoscopy despite adequate treatment with corticosteroids and/or immunomodulators and/or anti-TNF therapies. Patients were randomised (1:1) and stratified by body weight (BW) and prior anti-TNF use for induction to one of 2 weight range-based IV doses: 130mg vs. 390 mg if BW ≥40 kg and 3mg/kg vs. 9 mg/kg if BW &lt;40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW &lt;40 kg. UST PK outcomes were assessed and compared with adult Phase 3 CD trials. Results 44 patients (59% ≥40 kg; &gt;90% anti-TNF exposed) were randomised and treated with UST (n = 23 lower dose; n = 21 higher dose). Baseline demographics were generally similar between treatment groups. Most patients (67%) had a severe CD (PCDAI &gt;40). At weeks 0 (1 h after infusion), 3, 6, and 8, mean serum UST concentrations (SUC) in the lower- (51.3, 7.7, 3.0, 1.6 μg/ml) and higher-dose groups (149.0, 23.7, 9.1, 4.8 μg/ml) were generally dose proportional (Figure 1a). Following SC UST at week 8, the impact of the difference in induction doses had diminished by week 16 when mean SUC was 1.5 µg/ml in the lower-dose group vs. 1.8 µg/ml in the higher-dose group. In the overall paediatric population (combined doses), serum UST concentrations were comparable to those in the reference adult CD studies (Figure 1b and c). In the higher dose group, we observed a pattern toward lower mean serum UST concentrations in patients weighing &lt;40 kg vs. those weighing ≥40 kg; thus, UST should be dosed higher in patients &lt;40 kg. Overall at week 8 and week 16, more patients achieved clinical response (PCDAI reduction ≥15) and biomarker improvement with higher UST concentrations, although this pattern was not observed for clinical remission (PCDAI ≤10; Figure 2). Conclusion Overall, UST PK was generally comparable between paediatric and adult patients with CD. A trend towards better efficacy outcomes with higher UST concentrations was observed in children similar to adults with CD.

scholarly journals Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1012
Author(s):  
Melinda Moriczi ◽  
Gemma Pujol-Muncunill ◽  
Rafael Martín-Masot ◽  
Santiago Jiménez Treviño ◽  
Oscar Segarra Cantón ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Disease Activity ◽  
Clinical Remission ◽  
Activity Index ◽  
Newly Diagnosed ◽  
Faecal Calprotectin ◽  
Exclusive Enteral Nutrition ◽  
Paediatric Crohn’S Disease

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014–2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6–8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn’s Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (μg/g) decreased significantly after EEN (830 [IQR 500–1800] to 256 [IQR 120–585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 μg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6–8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn’s disease regardless of the location of disease and disease activity.

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