scholarly journals Vedolizumab in Combination With Corticosteroids for Induction Therapy in Crohn’s Disease: A Post Hoc Analysis of GEMINI 2 and 3

2019 ◽  
Vol 25 (8) ◽  
pp. 1375-1382 ◽  
Author(s):  
Bruce E Sands ◽  
Gert Van Assche ◽  
David Tudor ◽  
Gamar Akhundova-Unadkat ◽  
Rebecca I Curtis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Activity Index ◽  
Combined Therapy ◽  
Disease Activity Index ◽  
Efficacy And Safety ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background Combined therapy with vedolizumab and corticosteroids may improve clinical response or remission in Crohn’s disease. The aim of this study is to assess efficacy and safety/tolerability of vedolizumab plus stable doses of corticosteroids at baseline during induction therapy in moderately to severely active Crohn’s disease. Methods A post hoc exploratory analysis was performed on data from GEMINI 2 (NCT00783692) and GEMINI 3 (NCT01224171), which assessed outcomes following induction therapy over 6- and 10-week periods, respectively. Patients receiving vedolizumab or placebo were stratified by corticosteroid use at baseline. Efficacy endpoints were clinical remission (CR; Crohn’s Disease Activity Index [CDAI] score ≤150 points) and enhanced clinical response (ECR; decrease of ≥100 points in CDAI score from baseline), assessed at week 6 (GEMINI 2 and GEMINI 3) and week 10 (GEMINI 3). Safety endpoints included the incidence of adverse events. Results Vedolizumab plus corticosteroids resulted in higher CR rates than placebo plus corticosteroids at week 6 in GEMINI 2 and at week 6 and week 10 in GEMINI 3. More patients receiving vedolizumab plus corticosteroids achieved CR at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Vedolizumab plus corticosteroids also resulted in significantly higher ECR rates than placebo plus corticosteroids at all timepoints in both studies. More patients receiving vedolizumab plus corticosteroids achieved higher ECR rates at week 6 in GEMINI 2 and at week 10 in GEMINI 3 than patients receiving vedolizumab alone. Adverse event incidence was similar across groups. Conclusions Vedolizumab in combination with stable doses of corticosteroids at baseline may improve induction of clinical response or remission in moderately to severely active Crohn’s disease. Trial registration numbers NCT00783692, NCT01224171.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] <150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score <3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

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

Body Mass Index Does Not Impact Clinical Efficacy of Ustekinumab in Crohn’s Disease: A Post Hoc Analysis of the IM-UNITI Trial

2020 ◽  
Author(s):  
Emily C L Wong ◽  
John K Marshall ◽  
Walter Reinisch ◽  
Neeraj Narula
Keyword(s):  
Body Mass Index ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Body Mass ◽  
Clinical Efficacy ◽  
Activity Index ◽  
Linear Trend ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Impact

Abstract Background This post hoc analysis aimed to evaluate the impact of BMI on the efficacy of ustekinumab in the IM-UNITI study. Methods The relationship between body mass index (BMI) and efficacy of ustekinumab was evaluated using data from a 44-week maintenance study of ustekinumab in Crohn’s disease (IM-UNITI, NCT01369355, YODA #2019–4105). The primary endpoints of interest were clinical remission (CR), defined as Crohn’s disease activity index <150 and corticosteroid-free CR at week 44. Patients were stratified into the following subgroups according to their BMI at study entry: underweight <18.5 kg/m2, normal 18.5 to 25 kg/m2, overweight 25 to <30 kg/m2, and obese ≥30 kg/m2. The χ 2 test of linear trend was conducted for comparisons of frequencies between the 3 cohorts. Multivariate regression analyses evaluated possible association between BMI and efficacy outcomes of CR and corticosteroid-free CR, with adjustment for variables found significant on univariate analyses. Results are presented as odds ratios with 95% confidence intervals. Data were analyzed using Stata/IC 15. Results A total of 254 patients treated with ustekinumab were included in this analysis. At week 44 of IM-UNITI, rates of CR did not differ among those whose BMI was underweight (67.9%%; 19 of 28 patients), normal (51.3%; 60 of 117), overweight (45.1%; 32 of 71), or obese (55.3%; 21 of 38; P = 0.89). Multivariate logistic analysis did not find BMI to be a significant predictor of CR when adjusted for covariates. Ustekinumab drug level at week 44 was significantly lower in obese patients (median level 2.98 mcg/mL; interquartile range [IQR], 2.86) compared with patients who were overweight (4.84 mcg/mL; IQR, 3.51; P = 0.021) or had underweight or normal BMI (4.43 mcg/m;, IQR, 2.82; P = 0.014). Conclusions Although BMI impacts ustekinumab drug levels, there was no impact of BMI on clinical efficacy. Further studies of the pharmacodynamic effects of ustekinumab in patients with high BMI are needed.

scholarly journals Induction of Remission in Pediatric Crohn’s Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index

2021 ◽  
Vol 10 (23) ◽  
pp. 5613
Author(s):  
Roma Herman ◽  
Paulina Dumnicka ◽  
Stanisław Pieczarkowski ◽  
Krzysztof Fyderek
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Induction Therapy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Fecal Calprotectin ◽  
Mucosal Healing ◽  
Mucosal Inflammation ◽  
Exclusive Enteral Nutrition

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

scholarly journals OP36 Risankizumab therapy induces improvements in endoscopic endpoints in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S033-S034
Author(s):  
P Bossuyt ◽  
M Ferrante ◽  
F Baert ◽  
S Danese ◽  
B G Feagan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Induction Therapy ◽  
Activity Index ◽  
Inadequate Response ◽  
Biologic Treatment ◽  
Double Blind ◽  
Clinical Endpoints ◽  
Endoscopic Remission

Abstract Background Endoscopic healing has become a critical treatment target in Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin 23, is being investigated as a treatment for moderate-to-severe CD. This analysis assessed different endoscopic endpoints in patients treated with RZB induction therapy in two double-blind, randomised, 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 demonstrated prior inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE) or to biologic treatment (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous (IV) RZB 600 mg, RZB 1200 mg, or PBO at weeks 0, 4, and 8. This analysis evaluated the proportion of patients who achieved endoscopic remission ulcer-free endoscopy (ie, absence of ulcers), and composite endpoints of CDAI clinical response and endoscopic response, and enhanced clinical response and endoscopic response at week 12 (endpoints defined in Figure 1 footnotes). All endoscopies were centrally read by a blinded reviewer. Safety was assessed throughout the studies. Results In ADVANCE and MOTIVATE, 850 and 569 patients, respectively, were randomised and included in the intent-to-treat population for this analysis. At week 12 greater proportions of RZB- vs PBO-treated patients in both studies achieved endoscopic remission (P ≤ .001), ulcer-free endoscopy (P ≤ .01), CDAI clinical response and endoscopic response (P ≤ .001), and enhanced clinical response and endoscopic response (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 IV RZB 600 mg or 1200 mg resulted in improved outcomes at week 12 compared with PBO as assessed by endoscopy and by composite endoscopic-clinical endpoints in patients with moderate-to-severe CD. References

scholarly journals DOP019 Effect of vedolizumab treatment on extraintestinal manifestations in patients with Crohn’s disease: a GEMINI 2 post hoc analysis

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S36-S38
Author(s):  
B.G. Feagan ◽  
W.J. Sandborn ◽  
J.-F. Colombel ◽  
S. O’Byrne ◽  
J.M. Khalid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extraintestinal Manifestations ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn’s disease: a retrospective study

2021 ◽  
Vol 14 ◽  
pp. 175628482110430
Author(s):  
Hee Seung Hong ◽  
Kyuwon Kim ◽  
Kyunghwan Oh ◽  
Jae Yong Lee ◽  
Seung Wook Hong ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Oral Administration ◽  
Clinical Response ◽  
Activity Index ◽  
Medical Center ◽  
Retrospective Chart Review ◽  
Asian Population ◽  
Aminosalicylic Acid ◽  
Parenteral Injection

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn’s disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn’s disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX ( p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration.

Sign in / Sign up

Export Citation Format

Share Document