P083 VALIDATION OF A NEW PHYSICIAN GLOBAL ASSESSMENT COLONOSCOPY SCORE (PGA-CS) FOR PEDIATRIC CROHN’S DISEASE

2019 ◽  
Vol 25 (Supplement_1) ◽  
pp. S39-S39
Author(s):  
Jeremy Adler ◽  
Acham Gebremariam ◽  
Sally J Eder ◽  
Kelley R French ◽  
Andrew A Singer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Global Assessment ◽  
Physician Global Assessment

P083 VALIDATION OF A NEW PHYSICIAN GLOBAL ASSESSMENT COLONOSCOPY SCORE (PGA-CS) FOR PEDIATRIC CROHN’S DISEASE

2019 ◽  
Vol 156 (3) ◽  
pp. S56-S57
Author(s):  
Jeremy Adler ◽  
Acham Gebremariam ◽  
Sally J. Eder ◽  
Kelley R. French ◽  
Andrew A. Singer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Global Assessment ◽  
Physician Global Assessment

scholarly journals A228 EVOLUTION OF MRE FINDINGS IN PAEDIATRIC PATIENTS WITH SMALL BOWEL CROHN’S DISEASE ON MAINTENANCE METHOTREXATE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 103-104
Author(s):  
A Kellar ◽  
N Carmen ◽  
M Greer ◽  
T Walters ◽  
A Griffiths ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Global Assessment ◽  
Activity Index ◽  
Severe Disease ◽  
Clinical Findings ◽  
Mild Disease ◽  
Surgical History

Abstract Background Observational data in children and RCT data in adults indicate that methotrexate (MTX) is associated with induction and maintenance of clinical remission in luminal Crohn’s disease, but efficacy in achieving intestinal healing has not been examined. Aims To examine the evolution of MRE signs of inflammation in children treated with MTX. Methods In this retrospective cohort study, we reviewed paediatric CD patients on maintenance MTX monotherapy for >4 months who underwent serial MREs between July 2010 and October 2015. MREs were reviewed by a radiologist blind to clinical data. Overall inflammatory activity on each MRE was scored as minimal, mild, moderate or severe, informed by the presence of bowel wall thickness, wall enhancement, T2 hyperintensity, comb sign, mesenteric edema, penetrating disease, stricturing, diffusion restriction and motility. The radiologist’s global assessment of change from MRE 1 to MRE 2 was scored as improved, unchanged or worsened. Clinical findings, disease activity (assessed by weighted paediatric CD activity index [wPCDAI]) and surgical history were also extracted from medical records by a clinician blind to MRE results. Results Thirty-five patients were included (median age at diagnosis 12 [IQR 11–14] years; 77% male; 60% inflammatory (B1), 17% stricturing (B2), 23% penetrating (B3) disease). Between baseline and follow-up MRE, wPCDAI (median 15 [IQR 7–43] decreased to 8 [IQR 0–18]; p=0.006) and CRP (median 9 [IQR 2–36] decreased to 5 [IQR 5–9]; p=0.013) and 74% (N=26) were in clinical remission (wPCDAI < 12.5) at MRE 2. MRE features that significantly improved from MRE 1 to 2 were comb sign from 63% (N=37) to 38% (N=14) (p=0.02) and penetrating disease from 14% (N=8) to 0 (p=0.03). After a median of 17 months (IQR 13–23), 51% (N=18) of patients improved, 29% (N=10) worsened and 20% (N=7) had no change based on the radiologist’s global assessment. Of the 21 patients with moderate/severe disease at MRE 1, 33% (N=7) had minimal/mild disease by MRE 2. 66% (N=14/21) continued to have moderate/severe disease at MRE 2. Additionally, a further 14% (N=2/14) of those with minimal/mild disease at baseline MRE progressed to moderate/severe disease at MRE 2. Complete details of change between MRE 1 and MRE 2 are displayed in Figure 1. Conclusions Despite signs of clinical improvement, many paediatric CD patients on maintenance MTX therapy for >4 months have unchanged or worsened MRE findings. This underscores the need for follow-up imaging in these cases. Funding Agencies None

scholarly journals P352 A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn’s disease. The Cross Pennine study II

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S372-S373
Author(s):  
M V Lenti ◽  
V Dolby ◽  
T Clark ◽  
V Hall ◽  
S Tattersall ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Propensity Score ◽  
Adverse Events ◽  
Clinical Response ◽  
Real World ◽  
Propensity Score Analysis ◽  
Physician Global Assessment ◽  
Real World Data ◽  
The Difference

Abstract Background The best choice of biological agents after failure to an anti-tumour necrosis factor (TNF)α agent in patients with Crohn’s disease (CD) is yet to be defined. Real-world data dealing with this issue are still emerging. Methods This is a multicentre retrospective study including eight UK hospitals (August 2014-April 2020). We retrospectively collected data of patients treated with ustekinumab. Clinical response and remission at 14 and 52 weeks evaluated through Physician Global Assessment (PGA) and adverse events were recorded. Predictors of clinical response were examined, and a propensity score-matched analysis with a cohort of patients treated with vedolizumab was performed. Results Overall, 282 patients (mean age 40±15, F:M ratio 1.7:1) treated with ustekinumab were included. Clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and by 162/259 patients (62.5%) at 52 weeks. The most common reason for discontinuation was either primary failure or loss of response, followed by the occurrence of adverse events and by the need for surgery. The rate of non-adherence was rather low (1.4%). Current smoking (OR 2.48, 95% CI 1.13-5.44; p=0.02), baseline PGA (OR 2.4, 95% CI 1.55-3.69, p<0.001), and use of steroids (OR 2.42, 95% CI 1.26-4.65, p=0.008) were associated with 52-week treatment failure. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without anti-TNFα exposure prior to starting ustekinumab or vedolizumab and exclusion of patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) from the ustekinumab cohort and 118/135 patients (87.4%) from the vedolizumab cohort. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25-50%; p<0.001) more likely to achieve a clinical remission, while at 52 weeks, the difference of 9% (95% CI -15-33%; p=0.462) was not significant. Conclusion Ustekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-week follow-up, we found no statistically significant differences in outcomes at 52 weeks.

scholarly journals P312 Erythrocyte methotrexate polyglutamate concentrations in patients with Crohn’s Disease: towards a new therapeutic drug monitoring tool

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S339-S339
Author(s):  
M Van de Meeberg ◽  
M Lin ◽  
M Seinen ◽  
H Fidder ◽  
B Oldenburg ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Drug Monitoring ◽  
Cross Sectional Study ◽  
Individual Species ◽  
Therapeutic Drug ◽  
Physician Global Assessment ◽  
Cross Sectional ◽  
Large Variability

Abstract Background Methotrexate (MTX) is an immunomodulatory drug for patients with Crohn’s Disease (CD), used as first-line therapy, as a second-line in case of failure to thiopurine, and concomitantly with anti-TNFα agents to decrease production of anti-drug antibodies. Nevertheless, MTX is underutilised in the treatment of CD, despite its proven efficacy and good safety profile. This is for a large part due to the lack of therapeutic drug monitoring (TDM) of MTX because no stable plasma MTX levels are reached. Intracellular MTX-polyglutamates (MTX-PGs), formed after folylpolyglutamate synthetase attaches glutamate residues to MTX, could be used as a TDM tool as MTX-PG is thought to mediate MTX’s efficacy. We present the results of our cross-sectional study in CD patients, aiming to gain insight into erythrocyte MTX-PG levels. Methods CD adults on MTX treatment who visited the outpatient clinic of Amsterdam UMC between May 2019 and February 2020 were included consecutively. An established LC-ESI-MS/MS method1 was used to measure erythrocyte MTX-PGs. Results Nineteen patients were included. Mean disease duration was 17 years (SD±13.7). Montreal disease location and behaviour were as follows (n=): L1 = 2, L2 = 4, L3 = 13; B1 = 11, B2 = 5, B3 = 3. Only 4 patients had a flare according to Physician Global Assessment. Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant anti-TNFα agents. The mean dose of MTX was 15.5 mg (SD±2.8) and 12 (63%) patients had subcutaneous (sc.) MTX. We successfully measured MTX-PG2-5 in 18 patients, showing substantial variability in measured concentrations of total MTX-PG(tot) and the individual species. The median MTX-PGtot was 117.1 nmol/L [min:46.4-max:358.7] with preferential accumulation of MTX-PG3 (43.1 [15.3-96.1]); the least predominant species being MTX-PG5 (9.4 [1.1-24.1]). Patients on sc. compared to oral MTX had higher MTX-PGtot levels (177.8 [58.8-358.7] vs. 93.2 [46.4-120.8] nmol/L, p=0.067) and significantly higher long-chain MTX-PG4-5 levels (55 [3.7-84.3] vs. 8.9 [2.4-15.0] nmol/L, p=0.010); see figure. Conclusion We showed that erythrocyte MTX-PGs can be measured in CD patients by tandem MS. Large variability in concentrations was demonstrated, similar to our previously published results in rheumatoid and juvenile arthritis2,3 which is a pre-requisite for MTX-PG use as a TDM tool. We showed for the first time that MTX-PG accumulation was higher in sc. MTX vs. oral MTX treatment. This work provides the first step towards establishing TDM for MTX in CD, a goal we aim to realize in our upcoming longitudinal study. References

scholarly journals Lengthening adalimumab dosing interval in quiescent Crohn’s disease patients: protocol for the pragmatic randomised non-inferiority LADI study

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e035326
Author(s):  
L J T Smits ◽  
R W M Pauwels ◽  
W Kievit ◽  
D J de Jong ◽  
A C de Vries ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Cost Effectiveness ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Disease Activity ◽  
Cumulative Incidence ◽  
Control Group ◽  
Physician Global Assessment ◽  
Dosing Interval

IntroductionAdalimumab is effective for maintenance of remission in patients with Crohn’s disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW).Methods and analysisThe Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness.Ethics and disseminationThe study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences.Trial registration numbersEudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).

scholarly journals Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

2020 ◽  
Vol 13 ◽  
pp. 175628482095924
Author(s):  
Syedreza A. Haider ◽  
Abhijeet Yadav ◽  
Courtney Perry ◽  
Leon Su ◽  
Olalekan Akanbi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dose Escalation ◽  
Disease Duration ◽  
Biologic Therapy ◽  
Physician Global Assessment ◽  
Standard Dosage ◽  
Time Period ◽  
Label Dose ◽  
Clinical Responses

Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 ( p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL ( p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

scholarly journals P575 Real-world effectiveness and safety of ustekinumab for the treatment of refractory Crohn’s disease: The Scottish ustekinumab cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S484-S484
Author(s):  
N PLEVRIS ◽  
A Robertson ◽  
J Fulforth ◽  
R Hall ◽  
I Campbell ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Mucosal Inflammation ◽  
Physician Global Assessment ◽  
Serious Adverse Events ◽  
Objective Evidence

Abstract Background Ustekinumab (UST) is an anti-IL12/23 biologic licensed for the treatment of moderate to severe Crohn’s disease (CD). The aims of this study were to establish the long-term real-world effectiveness and safety of UST for the treatment of CD in a large UK cohort. Methods This was a multicentre retrospective cohort study , including 7 NHS health-boards in Scotland. Patients treated with UST between November 2015 and June 2019 were identified. Inclusion criteria included: a diagnosis of CD; active symptoms attributed to CD with objective evidence of mucosal inflammation (CRP &gt;5mg/l or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/ MRI); and completion of induction with a minimum of 8 weeks follow-up. Clinical assessments were performed based on physician global assessment (response was defined as ≥50% reduction in CD-related symptoms and remission defined as complete resolution of all CD-related symptoms). Mucosal healing was defined as the absence of ulceration/erosions on ileo-colonoscopy or no inflammation on MRI if ileo-colonoscopy was not possible (eg. B2 disease). Deep remission was defined as clinical remission plus mucosal healing. Rates of serious adverse events (discontinuation of UST, hospitalisation or death) during follow-up were described quantitively. Results A total of 207 patients (43% male; median age 39.2 years, IQR 28.9–51.4; median disease duration 10.0 years, IQR 5.7–16.6) with a median follow-up of 34.6 weeks (IQR 16.9–52.1) were included. The majority of patients had ileocolonic disease (L1, 19.3%; L2, 23.7%; L3, 57%) and an inflammatory phenotype (B1, 43.0%; B2, 41.1%; B3, 15.9%). A total of 98.6% of patients had previously been exposed to a biologic and 55.1 % had undergone previous surgery. Seventy-one per cent of patients received Q8 maintenance dosing, whilst 25.6% and 42.0% of patients were also receiving an immunomodulator (IMM) and steroids at initiation, respectively. At week 8, clinical response and remission rates were 51.7% and 5.8%, respectively. Twelve-month cumulative rates of clinical remission, mucosal healing (n = 116) and deep remission (n = 116) were 29.8%, 35.3% and 17.9%, respectively (Figure 1). During 155 patient-years of follow-up (PYF), 11 patients experienced a serious adverse event (7.1 per 100 PYF). Conclusion We have shown in a large real-world cohort of complex, treatment-refractory CD patients that UST is a safe and effective treatment option.

Sign in / Sign up

Export Citation Format

Share Document