scholarly journals Effect of vedolizumab dose intensification on serum drug concentrations and regain of response in inflammatory bowel disease patients with secondary loss of response

GastroHep ◽  
2021 ◽  
Author(s):  
A Outtier ◽  
L Wauters ◽  
JF Rahier ◽  
P Bossuyt ◽  
A Colard ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Dose Intensification ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Drug Concentrations ◽  
Inflammatory Bowel

scholarly journals P277 Frequency and effectiveness of empirical anti-TNF dose intensification in Inflammatory Bowel Disease: systematic review with meta-analysis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S309-S309
Author(s):  
L Guberna Blanco ◽  
O P Nyssen ◽  
M Chaparro ◽  
J P Gisbert
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Medical Condition ◽  
Cochrane Library ◽  
Therapeutic Drug ◽  
Dose Intensification ◽  
Loss Of Response ◽  
Subgroup Analyses ◽  
Inflammatory Bowel

Abstract Background Loss of response to anti-TNF (tumor necrosis factor) therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remains unclear. Our aims were: 1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; 2) To evaluate possible variables influencing its requirement; 3) To assess the effectiveness of empirical DI. Methods Bibliographical searches were performed in Pubmed, Embase, the Cochrane Library and CINAHL. Selection: prospective and retrospective studies assessing loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug [infliximab (IFX), adalimumab (ADA), certolizumab or golimumab]. Exclusion criteria: studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data synthesis: Effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (UC vs. CD), anti-TNF drug and follow-up. Subgroup analyses were performed to explore heterogeneity. Results In total, 174 studies (32,031 patients) were included. The overall rate of DI requirement after 12 months follow-up was 27% (95%CI 23-31, I2=96%, 51 studies) in naïve patients and 38% (95%CI 31-46, I2=87%, 18 studies) in non-naïve patients. The rate of DI requirement was higher in patients with prior anti-TNF exposure (c²=6.5, P=0.01) and in UC patients (c²=4.7, P=0.03). The rate of DI requirement in naïve patients after 36 months follow-up was 35% (95%CI 27-43%; I2=98%; 22 studies). The overall short-term response and remission rates to empirical DI in naïve patients were 66% (95%CI 61-71%; I2=81%; 35 studies) and 48% (95%CI 35-62%; I2=97%; 27 studies), respectively. Subgroup analyses are presented in the tables. Conclusion Loss of response to anti-TNF agents ―and consequent DI― occur frequently in IBD (approximately in 1/4 at one year and in 1/3 at 3 years). DI requirement is higher in UC patients and in those with prior anti-TNF exposure. Empirical DI is a relatively effective therapeutic option.

scholarly journals Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease

2018 ◽  
Vol 24 (11) ◽  
pp. 2461-2467 ◽  
Author(s):  
Eugenia Shmidt ◽  
Gursimran Kochhar ◽  
Justin Hartke ◽  
Prianka Chilukuri ◽  
Joseph Meserve ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Bowel Disease ◽  
C Reactive Protein ◽  
Dose Intensification ◽  
Reactive Protein ◽  
Loss Of Response ◽  
Increased Risk ◽  
Tnf Antagonist ◽  
Inflammatory Bowel

Abstract Background We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods Retrospective review (May 2014–December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn’s disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25–2.97] in all patients. For Crohn’s disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01–1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.

P082 ANTI-TNF EFFICACY AFTER PRIMARY VEDOLIZUMAB FAILURE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S71-S72
Author(s):  
Michael Dolinger ◽  
Priya Rolfes ◽  
Becky Phan ◽  
Stephanie Pan ◽  
Marla Dubinsky
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Median Duration ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Inflammatory Bowel ◽  
Pediatric Ibd

Abstract Background Vedolizumab (VDZ) is less effective in Inflammatory Bowel Disease (IBD) when used in anti-Tumor Necrosis Factor (TNF) failures as compared to anti-TNF naïve patients. However, the outcomes of sequencing anti-TNF after VDZ failure remain unknown. We report on the effectiveness and safety of anti-TNF as a second-line biologic after VDZ failure in pediatric IBD patients. Methods Data was collected as part of an ongoing pediatric IBD observational treatment registry and included demographics, disease behavior, location, disease activity (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) or partial Mayo score (pMS) for ulcerative colitis (UC) and IBD-unspecified (IBD-U)), adverse events, treatment and surgical history. Primary outcome was steroid-free clinical remission at last follow up. Secondary outcomes were CRP normalization and adverse events including infusion reactions, infections, hospitalizations, and IBD related surgeries. Descriptive statistics summarized the data (median [interquartile range (IQR)]) and univariate analyses tested associations. Results A total of 21 children and young adults (6 CD:14 UC:1 IBD-U; 19/21 colonic only disease) were treated with VDZ for a median [IQR] duration of 25 [11–59] weeks. VDZ was discontinued due to primary non-response (57%), secondary loss of response (38%), or an adverse event (5%). Nineteen (90%) patients were induced with infliximab (IFX), 1 with adalimumab, and 1 with golimumab and were followed for a median of 100 [35–148] weeks after anti-TNF induction (Table 1). Fifteen (71%) patients remained on anti-TNF therapy at last follow up for a median duration of 53 [34–112] weeks. All 15 patients achieved steroid-free clinical remission, and 9 (60%) patients also had a normal CRP (Figure 1). Remission rates were numerically higher in UC/IBD-U vs. CD (80% vs. 50% P = 0.27). All 6 (28%) patients (3 CD and 3 UC) who discontinued anti-TNF therapy after a median duration of 15 [7–24] weeks initially had a primary non-response to VDZ. Three patents had a primary non-response to anti-TNF, 2 had a secondary loss of response, and 1 had an anaphylactic infusion reaction. No serious adverse events, hospitalizations or serious infections attributable to anti-TNF therapy occurred. Conclusions Our results suggest that anti-TNF therapy is efficacious and safe after primary failure with VDZ in pediatric IBD patients and this was particularly so in patients with colonic disease location, regardless of IBD classification.

scholarly journals P573 Frequency and effectiveness of empirical anti-TNF dose intensification in inflammatory bowel disease: an on-going systematic review with meta-analysis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S482-S483
Author(s):  
L Guberna Blanco ◽  
O P Nyssen ◽  
M Chaparro ◽  
J P Gisbert
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Option ◽  
Random Effect ◽  
Random Effect Model ◽  
Therapeutic Drug ◽  
Dose Intensification ◽  
Loss Of Response ◽  
Inflammatory Bowel

Abstract Background Loss of response to anti-TNF therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remain unclear. Our aims were: (1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; (2) To evaluate possible variables influencing its requirement; (3) To assess the effectiveness of empirical DI. Methods Bibliographical searches were performed until January 2019. Selection: prospective and retrospective studies assessing the loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: Studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data were analyzed by means of the inverse variance method using a random effect model and stratifying by medical baseline condition (UC vs. CD), anti-TNF drug and follow-up. Effectiveness was assessed by intention-to-treat analysis. Results Up to now, 107 studies (11,377 patients) were included. The overall rate of DI requirement for naïve patients after 12 and 36 months of follow-up was 35% (95% CI=26–45%, I2=95%, 15 studies) and 48% (41–55%, I2= 77%, 9 studies); respectively. Frequencies of DI requirement stratified by subgroup analysis are presented in the table (all patients being naïve except CD patients treated with adalimumab (ADA), including naïve and no naïve). The overall short-term response and remission rates to empirical DI were 67% (95% CI: 63–72%; I2=73%; 31 studies) and 45% (95% CI: 35–55%; I2=9%; 23 studies), respectively; subgroup analyses are summarised in the table. Conclusion Loss of response to anti-TNF agents and consequent DI occurs frequently in both UC and CD, with an overall rate of DI requirement of 35% at one year and 48% at 3 years. Empirical DI is a relatively effective therapeutic option. Further data extraction and analysis is necessary to confirm these findings.

scholarly journals Frequency and Effectiveness of Empirical Anti-TNF Dose Intensification in Inflammatory Bowel Disease: Systematic Review with Meta-Analysis

2021 ◽  
Vol 10 (10) ◽  
pp. 2132
Author(s):  
Laura Guberna ◽  
Olga P. Nyssen ◽  
María Chaparro ◽  
Javier P. Gisbert
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Medical Condition ◽  
Therapeutic Drug ◽  
Dose Intensification ◽  
Loss Of Response ◽  
Inflammatory Bowel

Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn’s disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn’s disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn’s disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents―and, consequently, DI―occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option.

Sign in / Sign up

Export Citation Format

Share Document