Effectiveness of anti-TNFα drugs in patients with Crohn's disease who do not achieve remission with their first anti-TNFα agent

R-Grau, María del Carmen; Chaparro, María; Mesonero, Francisco; Acosta, Manuel Barreiro‐de; Castro, Luísa; Castro, Manuel; Domènech, Eugeni; Manceñido, Noemí; Pérez-Calle, J.L.; Taxonera, Carlos; Barrio, Jesús; Francisco, Ruth de; Fernández-Salgado, Estela; Luzón, Lara; Merino, Olga; Oltra, L.; Saro, Cristina; Bermejo, Fernando; García–Sánchez, Valle; Ginard, Daniel; Gutiérrez, Ana; Vera, Isabel; Antón, Rosario; Ber, Yolanda; Calvet, Xavier; Gisbert, Javier P.

doi:10.1016/j.dld.2016.02.012

Cited by 12 publications

(11 citation statements)

References 37 publications

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“…Sustained clinical response and remission beyond 12 months from the time of dose escalation were reported in 14 studies and ranged from 33% to 90% for response and 28%‐81% for remission 27,31,33‐36,41,42,45‐48,50,51 . Similar rates of loss of response to dose‐escalated treatment (tertiary loss of response) were reported across five studies 27,30,44,45,52 .…”

Section: Resultsmentioning

confidence: 68%

“…The majority of clinical efficacy data were from retrospective studies with subcohorts that underwent empiric dose escalation (without the use of TDM) for loss of response to standard treatment. Twenty studies reported clinical outcomes following empiric escalation of maintenance adalimumab 10,23‐41 . Response rates ranged from 33% to 100% (Figure 2), and remission was achieved in 15% to 83% of patients at any point after treatment escalation 10,23‐41 .…”

Section: Resultsmentioning

confidence: 99%

“…Twenty studies reported clinical outcomes following empiric escalation of maintenance adalimumab 10,23‐41 . Response rates ranged from 33% to 100% (Figure 2), and remission was achieved in 15% to 83% of patients at any point after treatment escalation 10,23‐41 . In 15 of these studies, more than half of the patients regained clinical response after dose escalation 23‐25,27‐32,35‐39,42 .…”

Section: Resultsmentioning

confidence: 99%

“…For infliximab, rates of clinical response and remission following empiric escalation for treatment failure ranged from 34% to 90% and 26% to 81%, respectively, across 12 studies (Figure 3). 28,31‐33,43‐50 In eight of these studies, intensified therapy recaptured response in over 50% of the patients 28,36,45‐50 . In one retrospective study (n = 265), a switch to adalimumab achieved numerically higher rates of clinical response (83.3%) than infliximab dose escalation (42.3%) 32…”

Section: Resultsmentioning

confidence: 99%

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Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Mattoo

Basnayake

Connell

et al. 2021

Aliment Pharmacol Ther

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Summary Background Loss of response to anti‐TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). Aims To perform a systematic review assessing the efficacy of escalated maintenance anti‐TNF therapy in CD. Methods EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full‐text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. Results A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%‐100%) and remission (15%‐83%) after empiric dose escalation for loss of response to standard anti‐TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose‐escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure‐response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end‐points. Strategies including Bayesian dashboard‐dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long‐term outcomes. Conclusions Empiric escalation of maintenance anti‐TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Mattoo

Basnayake

Connell

et al. 2021

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…Indeed, the likelihood of retention of treatment was 60% and 51% at 12 and 24 months after IFX reintroduction (median treatment duration of 16 months), respectively. Another study included 118 patients with CD who received anti-TNF therapy for the first time (median duration of treatment was 5 months), of whom 64 patients showed no response and 54 patients had only a partial response [ 32 ]. After these patients received a second anti-TNF treatment, 44% of the first-time non-responders achieved remission and 59% of the first-time partial responders achieved clinical remission.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Sequencing-Based Validation of T Cell-Associated Diagnostic Model Genes and Drug Response in Crohn’s Disease

Dai

Zhang

et al. 2023

IJMS

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Crohn’s disease is a highly heterogeneous autoimmune disease with a unique inflammatory phenotype of T cells at the lesion site. We aim to further explore the diagnosis of Crohn’s disease and drug prediction of T cell marker gene expression. We obtained single-cell expression profile data from 22 CDs or normal samples and performed cell annotation and cellular communication analysis. Through the intersection of T cell marker genes, differential genes, and WGCNA results, we identified T cell-specific key genes and their immune landscapes and potential pathogenesis, and validated them across multiple datasets and patient tissue samples. We also explored the differentiation characteristics of genes by pseudo-temporal analysis and assessed their diagnostic performance and drug sensitivity by molecular docking. Finally, we extended this study to the prognosis of IBD-associated colon cancer. TNF-centered 5-gene diagnostic model not only has excellent diagnostic efficacy, but is also closely associated with KRAS, P53, and IL6/JAK/STAT3 pathways and physiological processes, such as EMT, coagulation, and apoptosis. In addition, this diagnostic model may have potential synergistic immunotherapeutic effects, with positive correlations with immune checkpoints such as CTLA4, CD86, PDCD1LG2, and CD40. Molecular docking demonstrated that BIRC3 and ANXA1 have strong binding properties to Azathioprine and Glucoocorticoid. Furthermore, the 5-gene model may suggest antagonism to IFX and prognosis for colon cancer associated with inflammatory bowel disease. Single-cell sequencing targeting T cell-related features in patients with Crohn’s disease may aid in new diagnostic decisions, as well as the initial exploration of high-potential therapies.

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Immune rebalancing by oral immunotherapy: A novel method for getting the immune system back on track

Ilan

2018

Journal of Leukocyte Biology

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Immune modulating treatments are often associated with immune suppression or an opposing anti‐inflammatory paradigm. As such, there is a risk of exposing patients to infections and malignancies. Contrarily, eliciting only mild immune modulation can be insufficient for alleviating immune‐mediated damage. Oral immunotherapy is a novel approach that uses the inherent ability of the gut immune system to generate signals that specifically suppress inflammation at affected sites, without inducing generalized immune suppression. Oral immunotherapy is being developed as a method to rebalance systemic immunity and restore balance, getting it back on track, rather than pushing the immune response too much or too little in opposing directions. Here, I review recent preclinical and clinical data examining the technique and describe its primary advantages.

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Effectiveness of anti-TNFα drugs in patients with Crohn's disease who do not achieve remission with their first anti-TNFα agent

Cited by 12 publications

References 37 publications

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Single-Cell Sequencing-Based Validation of T Cell-Associated Diagnostic Model Genes and Drug Response in Crohn’s Disease

Immune rebalancing by oral immunotherapy: A novel method for getting the immune system back on track

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