Mo1850 - Lower Need for Adalimumab Dose Intensification in Inflammatory Bowel Disease Patients with Combined Immune Suppression Compared with Adalimumab Monotherapy

2018 ◽  
Vol 154 (6) ◽  
pp. S-825
Author(s):  
Jan Kovacs ◽  
Barbora Kadleckova ◽  
Laura Gombosova ◽  
Lucia Novotna ◽  
Erika Barlova ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Suppression ◽  
Bowel Disease ◽  
Dose Intensification ◽  
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.

scholarly journals Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response

2019 ◽  
Vol 11 (3) ◽  
pp. 188-193 ◽  
Author(s):  
Mark A Samaan ◽  
Siddharth Birdi ◽  
Maria Sierra Morales ◽  
Sailish Honap ◽  
Aravind Gokul Tamilarasan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Activity Index ◽  
Univariate Analysis ◽  
C Reactive Protein ◽  
Dose Intensification ◽  
Reactive Protein ◽  
Predictors Of Response ◽  
Proven Efficacy ◽  
Inflammatory Bowel

BackgroundDespite the proven efficacy of vedolizumab (VDZ) for ulcerative colitis (UC) and Crohn’s disease (CD), suboptimal response is commonly encountered. However, data regarding the effectiveness of dose intensification (by interval shortening) to achieve response are limited.ObjectivesWe evaluated the effectiveness of dose intensification at achieving response in patients with a previously suboptimal response to VDZ. Additionally, we aimed to identify predictors of response to this strategy.MethodsWe performed a retrospective cohort study of patients who underwent VDZ dose intensification for suboptimal response. Clinical disease activity was evaluated at the point of dose intensification (baseline) and at weeks 12 and 24. Response was defined as Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) reduction of ≥3, and remission as HBI <5 or SCCAI <3.ResultsA total of 36 patients received dose intensification to 4-weekly infusions: 18 CD, 14 UC and 4 inflammatory bowel disease-unclassified (analysed in the UC group). Median SCCAI scores fell from 6 (range 0–11) at baseline to 4 (0–6, p=0.008) at week 24, while HBI scores did not change significantly (4 (0–27) and 3 (0–8), p=0.092). Overall median C reactive protein (CRP) fell from 6 mg/L (1–23) to 2 mg/L (1–17, p=0.011). Of 20 patients with clinically active disease at baseline, 10 (50%) responded, of whom 4 (20%) achieved remission at week 24. Univariate analysis demonstrated low baseline CRP (p=0.045) and response at week 12 (0.020) were associated with week 24 response.ConclusionsOur findings demonstrate VDZ dose intensification to be effective at achieving clinical response in half of patients. Low baseline CRP and response at week 12 are potential predictors of week 24 response.

scholarly journals PTU-073 Dose Intensification with Anti-TNF Agents in Inflammatory Bowel Disease- a Secondary Care Experience

Gut ◽  
2013 ◽  
Vol 62 (Suppl 1) ◽  
pp. A74.2-A75
Author(s):  
G Kothegal Marimahadevappa ◽  
J K Limdi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Secondary Care ◽  
Dose Intensification ◽  
Care Experience ◽  
Inflammatory Bowel

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 Low Risk of Pneumonia From Pneumocystis jirovecii Infection in Patients With Inflammatory Bowel Disease Receiving Immune Suppression

2017 ◽  
Vol 15 (6) ◽  
pp. 850-856 ◽  
Author(s):  
Thomas G. Cotter ◽  
Nicola Gathaiya ◽  
Jelena Catania ◽  
Edward V. Loftus ◽  
William J. Tremaine ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Suppression ◽  
Bowel Disease ◽  
Low Risk ◽  
Pneumocystis Jirovecii ◽  
Inflammatory Bowel

scholarly journals COVID-19—from mucosal immunology to IBD patients

2021 ◽  
Author(s):  
Carl Weidinger ◽  
Ahmed Nabil Hegazy ◽  
Rainer Glauben ◽  
Britta Siegmund
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Immune Suppression ◽  
Bowel Disease ◽  
Digestive System ◽  
Viral Infections ◽  
Intestinal Epithelial Cells ◽  
Mucosal Immunology ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

AbstractViral infections with SARS-CoV-2 can cause a multi-facetted disease, which is not only characterized by pneumonia and overwhelming systemic inflammatory immune responses, but which can also directly affect the digestive system and infect intestinal epithelial cells. Here, we review the current understanding of intestinal tropism of SARS-CoV-2 infection, its impact on mucosal function and immunology and summarize the effect of immune-suppression in patients with inflammatory bowel disease (IBD) on disease outcome of COVID-19 and discuss IBD-relevant implications for the clinical management of SARS-CoV-2 infected individuals.

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.

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