scholarly journals P375 A simulation study to evaluate the performance of a multiple imputation method to address missing data in an analysis of clinical effectiveness using the ImproveCareNow Registry of pediatric patients with Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S391-S391
Author(s):  
N Zhang ◽  
C Liu ◽  
E King ◽  
S Chen ◽  
K Olano ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Missing Data ◽  
Crohn's Disease ◽  
Multiple Imputation ◽  
Clinical Remission ◽  
Pediatric Patients ◽  
Remission Rate ◽  
Base Case ◽  
Clinical Remission Rate ◽  
Complete Dataset

Abstract Background Patient registries are a source of real-world data (RWD) that are increasingly used to generate real-world evidence (RWE) for the safety and effectiveness of medical therapies. However, in registries, outcome data typically collected in clinical trials may be missing in some patients, creating a major challenge in evaluating RWD reliably. Clinical remission in pediatric Crohn’s disease (PCD), defined by the Short Pediatric Crohn’s disease Activity Index (sPCDAI) <10, is routinely collected in the ImproveCareNow (ICN) Registry, the world’s largest registry of pediatric patients with inflammatory bowel disease (IBD). A feasibility analysis of ICN as a RWD source to estimate the efficacy of therapies in PCD found about one-third of patients were missing at least 1 of the 6 components needed to calculate the sPCDAI scores at Week 52. We conducted a simulation study to evaluate the performance of the multiple imputation (MI) method in addressing the missing data issue. Methods A Starting Dataset from the ICN registry included CD patients age 2 to <18 yr when beginning treatment with a biologic agent other than ustekinumab during 2014 to 2019, who had a baseline visit and a “Week 52” visit. A Complete Dataset included only patients in the Starting Dataset who had all components required to calculate a sPCDAI score at the Week 52 visit. The true remission rate was calculated for the Complete Dataset. For the simulation, missing data patterns for individual sPCDAI components that were observed in the Starting Dataset were randomly imposed in the Complete Dataset. Variables that were predictive of sPCDAI scores, its components, and sPCDAI missingness were included. Ten thousand datasets were simulated for each of three scenarios: base case of the observed missingness in the Starting Dataset, 1.5 times the base case and 2 times the base case. The MI method was applied to the simulated datasets to estimate the remission rate. MI performance was measured by bias and coverage of the true remission rate from the Complete Dataset. Results The Starting and Complete Datasets included 1,458 and 1,212 patients, respectively. The true clinical remission rate in the Complete Dataset was 75.1% (95% CI: 72.6%-77.5%). Analysis without MI for the missing sPCDAI data resulted in underestimation of clinical remission rate, with bias about -2% to -5% (Table 1). The MI method eliminated the bias and had 100% coverage in all simulation scenarios by using a large number of independent predictors. Conclusion The MI method improved the validity, reliability, and efficiency of using RWD for estimating clinical remission in pediatric patients with CD and could be valuable in other registry studies.

scholarly journals DOP80 Effectiveness of ustekinumab and vedolizumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: A multi-centre comparative study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S118-S120 ◽  
Author(s):  
H Alric ◽  
A Amiot ◽  
J Kirchgesner ◽  
X Tréton ◽  
M Allez ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Propensity Scores ◽  
Remission Rate ◽  
University Hospitals ◽  
Clinical Remission Rate ◽  
Paris Area ◽  
History Of

Abstract Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn’s disease (CD) refractory to anti-TNF. In France between May 2014 and November 2016, vedolizumab (and not ustekinumab) was reimbursed for patients who had failed anti-TNF. Then, between December 2016 and August 2018, ustekinumab (and not vedolizumab) was reimbursed for this category of patients. Since September 2018, both ustekinumab and vedolizumab are reimbursed in patients who are refractory to anti-TNF. The aim of this study was to compare effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. Methods We studied all consecutive patients with active CD who were refractory to at least one anti-TNF, and were treated either with vedolizumab or ustekinumab, in five university hospitals of the Paris area, between May 2014 and August 2018. The primary endpoint was clinical remission rate at week 48. Adjustment according to propensity scores with inverse probability of treatment weighting was performed. Results 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. After propensity scoring with IPTW, there was no difference between the two groups (Figure 1). At week 48, the clinical remission rate was higher with ustekinumab than with vedolizumab (54.4% vs. 38.3%; OR =1.92, 95% CI [1.09–3.39]). At week 48, corticosteroid-free remission rate tended to be numerically higher with ustekinumab than with vedolizumab (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]). Treatment persistence was significantly more frequent in the ustekinumab group (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62]). The dose optimisation rate at week 48 was higher with vedolizumab than with ustekinumab (53.5% vs. 30.1%; OR = 0.37, 95% Cl [0.21–0.67]). Subgroup analyses showed that ustekinumab was associated with higher clinical remission rates at week 48 in patients with ileal CD (OR = 3.49; 95% CI [1.33–9.17]), a penetrating phenotype (OR = 6.58; 95% CI [1.91–22.68]) and a history of perianal disease (OR = 2.48; 95% CI [1.04–5.93]). Regardless of treatment group, combotherapy was associated with a higher clinical remission rate at week 48 (OR = 1.93; 95% CI [1.09–3.43]). Conclusion This study suggests that, after 1 year of follow-up, ustekinumab is associated with a higher rate of clinical remission than vedolizumab in CD patients refractory to anti-TNF, particularly in those with ileal and penetrating disease.

scholarly journals OP35 Effect of maintenance ustekinumab on corticosteroid-free endoscopic and clinical outcomes in patients with Crohn’s Disease - Week 48 analysis of the STARDUST trial

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S032-S033
Author(s):  
S Danese ◽  
S Vermeire ◽  
G D’Haens ◽  
J Panés ◽  
A Dignass ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Primary Endpoint ◽  
Clinical Remission ◽  
Response Rate ◽  
Remission Rate ◽  
Standard Of Care ◽  
Treat To Target ◽  
Clinical Remission Rate ◽  
Endoscopic Score

Abstract Background The STARDUST study demonstrated that ustekinumab (UST), using either a treat-to-target (T2T) or standard of care (SoC) strategy, may induce and maintain endoscopic and clinical response and remission in Crohn’s disease (CD). Primary endpoint, safety, and efficacy have been reported previously.1 Because corticosteroid (CS) sparing is an important aim of CD management, we compared the efficacy of UST T2T vs SoC in achieving CS-free clinical remission and endoscopic response. Methods Adult patients (pts) with moderate–severely active CD who were CDAI 70 responders after 16 weeks (W) of induction, comprising a single dose of UST 6 mg/kg iv followed by UST 90 mg SC at W8, were randomized to either T2T or SoC arms. In the T2T arm, choice of UST maintenance dosage (q12w or q8w) was based on endoscopic improvement at W16, followed by clinical and biomarker-directed dose escalation up to q4w; in the SoC arm, UST q12w or q8w dosage was based on EU SmPC. Primary endpoint was endoscopic response (Simple Endoscopic Score in CD [SES-CD] decrease from baseline [BL] ≥50%) at W48. For pts on CS at W16, CS tapering was mandatory. At W48, CS-free clinical remission (CDAI <150 and no CS for ≥30 days) and CS-free endoscopic response (reduction from BL in SES-CD ≥50% and no CS for ≥30 days) were evaluated. Results Of 500 pts enrolled, 441 achieved a CDAI 70 response at W16 and were randomized to T2T (n=220) or SoC (n=221); 79.1% and 87.3%, respectively, completed W48. Among clinical remitters and responders at W16 (start of CS tapering), in both T2T and SoC arms more than 70% were still in remission or response at W48 (Figure 1). CS use throughout 48 weeks of treatment is summarized in Table 1. At W48, in T2T and SoC arms similar rates were noted for CS-free endoscopic response (33.6% and 28.5%, respectively) and CS-free clinical remission (56.4% and 63.3%, respectively). Notably, in T2T and SoC arms the CS-free clinical remission rate among pts on CS at BL was 44.1% and 45.1%, respectively (Figure 2). Among W48 endoscopic responders (T2T, n=83; SoC, n=66), CS-free endoscopic response rate was 89.2% and 95.5%, respectively; among W48 clinical remitters (T2T, n=135; SoC, n=154), CS-free clinical remission rate was 91.9% and 90.9%, in T2T and SoC arms, respectively. Conclusion Pts treated with UST under T2T or SoC strategies achieved similar rates of CS-free clinical remission and endoscopic response over 48 weeks. Overall for pts on CS at BL, UST reduced the need for CS while achieving response/remission. Most (>89%) pts with endoscopic response/clinical remission at W48 were also CS-free responders/remitters. Reference

Sa1210 Relationship Between Adalimumab Concentration and Efficacy for the Induction of Clinical Remission in Pediatric Patients With Moderate to Severe Crohn's Disease

2013 ◽  
Vol 144 (5) ◽  
pp. S-230-S-231 ◽  
Author(s):  
Rajendra S. Pradhan ◽  
Shringi Sharma ◽  
Roopal Thakkar ◽  
Anne Robinson ◽  
Jeffrey S. Hyams ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Pediatric Patients

Sa1212 Relationship Between Adalimumab Concentration and Efficacy for the Maintenance of Clinical Remission in Pediatric Patients With Moderate to Severe Crohn's Disease

2013 ◽  
Vol 144 (5) ◽  
pp. S-231
Author(s):  
Shringi Sharma ◽  
Rajendra S. Pradhan ◽  
Roopal Thakkar ◽  
Anne Robinson ◽  
Jeffrey S. Hyams ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Pediatric Patients

scholarly journals A229 USTEKINUMAB FOR THE TREATMENT OF REFRACTORY PEDIATRIC CROHN’S DISEASE: A SINGLE CENTRE EXPERIENCE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 104-106
Author(s):  
A Cohen ◽  
A Sant’Anna ◽  
N Ahmed
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
The Other ◽  
Secondary Loss ◽  
Loss Of Response

Abstract Background Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population. Aims We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission. Methods We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score. Results Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders. Conclusions These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy. Funding Agencies None

Influence of Vitamin D3 Supplementation on Infliximab Efficacy in Chinese Patients With Crohn’s Disease: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Sheng-long Xia ◽  
Quan-jia Min ◽  
Xiao-xiao Shao ◽  
Dao-po Lin ◽  
Guo-long Ma ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Remission Rate ◽  
Chinese Patients ◽  
Cytokine Profiles ◽  
Clinical Remission Rate ◽  
Tnf Α ◽  
Vitamin D3 Supplementation ◽  
The Mean

Abstract Background: It remains uncertain whether vitD3 supplementation is beneficial for remission of Crohn’s disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) efficacy was retrospectively analyzed in Chinese CD patients.Methods: Patients with moderate-to-severe CD, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks were recorded. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention.Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (P<0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (P=0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (P=0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (P=0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3, but not in non-deficient vitD3. In non-D3-patients, the decreases of IL-6 and TNF-α at 54-week were more obvious than at baseline (both P<0.05). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P=0.037).Conclusions: VitD3 supplementation could not only improve IFX efficacy, especially for patients with vitD3 deficiency, but also affected the cytokine profiles in CD patients. (Clinical Trials. Gov NCT04606017)

scholarly journals The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn’s Disease: Experience from a Tertiary Medical Center in China

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Tianyu Zhang ◽  
Zhengting Wang ◽  
Rong Fan ◽  
Maochen Zhang ◽  
Yun Lin ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Remission Rate ◽  
Therapy Group ◽  
Sequential Therapy ◽  
Sequential Treatment ◽  
Monotherapy Group ◽  
Endoscopic Remission ◽  
Remission Rates

Objective.To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn’s disease (CD) patients.Methods.Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups.Results.A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P=0.004and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P>0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P>0.05).Conclusion.IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen.

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