scholarly journals Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study

2021 ◽  
Vol 10 (13) ◽  
pp. 2914
Author(s):  
Ahmad Albshesh ◽  
Joshua Taylor ◽  
Edoardo V. Savarino ◽  
Marie Truyens ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Therapy Group ◽  
Multicenter Cohort Study ◽  
Biologic Treatment ◽  
Tumor Necrosis Factors ◽  
Group A ◽  
Group B

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

scholarly journals OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S026-S027
Author(s):  
S W Schreiber ◽  
M Ferrante ◽  
R Panaccione ◽  
J F Colombel ◽  
T Hisamatsu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Clinical Remission ◽  
Activity Index ◽  
Unmet Need ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

Mo1896 The Real-Life Experience of Vedolizumab Efficacy and Safety in Crohn's Disease: A Prospective Observational Multicenter Cohort Study

2016 ◽  
Vol 150 (4) ◽  
pp. S810
Author(s):  
Aurelien Amiot ◽  
Jean-charles Grimaud ◽  
Xavier Treton ◽  
Jerome Filippi ◽  
Benjamin Pariente ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Life Experience ◽  
Real Life ◽  
Efficacy And Safety ◽  
Multicenter Cohort Study ◽  
The Real ◽  
Multicenter Cohort

scholarly journals Factors associated with time to clinical remission in pediatric luminal Crohn's disease: A retrospective cohort study

JGH Open ◽  
2021 ◽  
Author(s):  
Samuel Sassine ◽  
Souhila Zekhnine ◽  
Marwa Qaddouri ◽  
Lisa Djani ◽  
Christine Cambron‐Asselin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Retrospective Cohort Study ◽  
Clinical Remission ◽  
Retrospective Cohort ◽  
Factors Associated

scholarly journals Dietary Triggers of Gut Inflammation Following Exclusive Enteral Nutrition in Children with Crohn’s Disease: A Pilot Study

2021 ◽  
Author(s):  
Konstantinos Gkikas ◽  
Michael Logan ◽  
Ben Nichols ◽  
Umer Z. Ijaz ◽  
Clare M. Clark ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Pilot Study ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Processed Meat ◽  
Faecal Calprotectin ◽  
Exclusive Enteral Nutrition ◽  
Group A ◽  
Group B ◽  
Red And Processed Meat

Abstract Objectives:The anti-inflammatory effect of exclusive enteral nutritionon thegut of children with Crohn’s disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition.Methods: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn’s disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. Results:Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B;(median [Q1, Q3], grams; Fibre: 12.1 [11.2, 19.9] vs 9.9 [7.6, 12.1], p=0.03; Red and processed meat: 151 [66.7, 190] vs 63.3[21.7, 67], p=0.02; gluten-containing cereals: 289 [207, 402] vs 203 [61, 232], p=0.035). A diet consisting ofcereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance,were higher in Group A than Group B by 28.4 μmol/g (p=0.015)and 6.4% (p=0.008), respectively.Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. Conclusions:This pilot study identified potential dietary triggers of gut inflammation in children with Crohn’s disease after food reintroduction following treatment with exclusive enteral nutrition.Trial registration: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL:https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered)

scholarly journals P672 A tertiary multicenter cohort of patients with chronic intestinal pseudo-obstruction and Crohn’s disease: a rare association with a high prevalence of monogenic disorders

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S593-S594
Author(s):  
F De castelbajac ◽  
F Charbit-Henrion ◽  
O Goulet ◽  
N Cerf-Bensussan ◽  
X Treton ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Rare Condition ◽  
Intraepithelial Lymphocytes ◽  
Sustained Remission ◽  
Biologic Treatment ◽  
High Prevalence ◽  
Intestinal Pseudo Obstruction ◽  
Immune Defects

Abstract Background Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD). We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD. Methods We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers. Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included. We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies Results Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15–35 umol/l). Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient. Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission. Conclusion Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.

scholarly journals DOP74 Effectiveness of dose escalation in Crohn’s disease patients with insufficient response to standard-dose subcutaneous ustekinumab maintenance therapy: A multicentre international cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S111-S112 ◽  
Author(s):  
U Kopylov ◽  
J Hanzel ◽  
C Liefferinckx ◽  
D De Marco ◽  
N Imperatore ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Median Duration ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Standard Dose ◽  
Dose Interval ◽  
Insufficient Response

Abstract Background Ustekinumab (UST) is an effective agent for induction and maintenance of response and remission in Crohn’s disease (CD). In addition to randomised controlled trials, an abundance of real-world evidence is available as well, suggesting that a substantial proportion of patients will not respond or lose response to UST therapy. To date, there is very little evidence to support the effectiveness of dose-optimisation strategy to manage primary or secondary non-response to ustekinumab. Methods This was a multicentre retrospective cohort study. The protocol was reviewed and approved by the Clinical Committee of ECCO. We included active (HBI≥5; CDAI ≥220) CD patients that received a standard-dose IV induction and at least one SC UST dose of 90 mg. Patients with ostomy were excluded. All patients received dose escalation by either shortening the interval between the doses to q4/6 weeks, intravenous reinduction or a combination of intravenous and subcutaneous escalation. The primary aim of the study was a clinical response (defined as Δ HBI≥3 or Δ CDAI ≥ 70 points) at week 16 after dose escalation. Clinical remission was defined as HBI<5 or CDAI <150. Results Of 140 patients, 83 (59.3%) were females, median age at treatment onset 36 (26–50) years, median duration of disease 9 (5–18) years from 21 centres in 13 countries (12 Europe, 1 Canada) were included. The patients were dose-escalated after a median treatment duration of 30 (20–45) weeks. Thirty-four (24,3%) were previously escalated from q12 to q8 maintenance regimen. Eighty-nine (63.5%) of the patients were escalated from q8 to q4 regimen, 20 (14.3%) – from q8 to q6, 15 (10.7%) received intravenous reinduction and 16 (11.4%) – a combination of intravenous reinduction and subcutaneous dose interval shortening. At week 16 from escalation, 83 (59.3%) responded to treatment, of them 21 (15%) were in clinical remission. Thirty-three (23.6%) of the patients were on systemic corticosteroids upon escalation; 7/33 (21.2%) achieved corticosteroid-free remission at week 16. One hundred and nine patients (77.8%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 75/150 (53.6%) of the patients (median duration of follow-up: 35 (32–54) weeks) from dose escalation. At the last follow-up, 53/75 (70.7%) continued to respond to treatment, including 42 (56%) in clinical remission; 25/75 (33%) discontinued treatment at last follow-up. Conclusion This large multicentre retrospective study demonstrates that intensification of ustekinumab maintenance dosage may be effective in up to 60% of the patients. This strategy should be considered in patients that are non-responsive to q8 ustekinumab maintenance dosing.

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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