Immunomodulator use does not prevent first loss of response to anti‐tumour necrosis factor alpha therapy in inflammatory bowel disease: long‐term outcomes in a real‐world cohort

Varma, Poornima; Rajadurai, Anton; Holt, Darcy; Devonshire, David; Desmond, Chris; Swan, Michael P.; Nathan, Debra; Shelton, Edward; Prideaux, Lani; Sorrell, Catherine; Rusli, Ferry; Crantock, Luke; Dev, Anouk; Ratnam, Dilip; Pianko, Stephen; Moore, Gregory T.

doi:10.1111/imj.14150

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…The median time to LOR was not different between groups. The data suggest that patients treated with anti-TNF monotherapy have similar LOR rates as patients on anti-TNF combination therapy (95). Switching to another anti-TNF may aid 50% of patients with IBD.…”

Section: Current Methods For Overcoming Ineffectiveness Of Anti-tnfs mentioning

confidence: 99%

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Khoury

Ilan

2019

Front. Immunol.

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Primary lack of response and secondary loss of response (LOR) are major obstacles to the use of anti–tumor necrosis factor (TNF)-based therapies in patients with rheumatoid arthritis or inflammatory bowel disease. Here, we review the mechanisms and methods for predicting LOR and the currently used methods for overcoming the ineffectiveness of anti-TNFs. The complex functions of TNF and anti-TNF antibodies, which can promote both pro- or anti-inflammatory actions, and the factors that affect the induction of immune tolerance to their effects are presented. The lack of rules and the continuous dynamics of the immune processes partly underlie the unpredictability of the response to anti-TNFs. Variability is inherent to biological systems, including immune processes, and intra/inter-patient variability has been described in the response to drugs. This variability is viewed as a compensatory adaptation mechanism of the immune system in response to drugs and may contribute to treatment LOR. Dose reductions and drug holidays have been tested in patients treated with anti-TNFs. Regular dose-based regimens may be incompatible with physiological variability, further contributing to treatment inefficacy. We present the concept of overcoming immune system adaptation to anti-TNFs by introducing patient-tailored patterns of variability to treatment regimens.

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Section: Current Methods For Overcoming Ineffectiveness Of Anti-tnfs mentioning

confidence: 99%

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Khoury

Ilan

2019

Front. Immunol.

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“…About 50% of subjects with Crohn’s disease or ulcerative colitis develop LOR to infliximab following an early response to the drug [ 82 ]. There is no difference in time to LOR between subjects treated using regimens comprising several drugs or different anti-TNF agents [ 83 ]. Switching between anti-TNF agents, dose intensification, and adding an immunomodulator to suppress immunogenicity may overcome LOR with moderate success [ 84 , 85 ].…”

Section: Drug Resistance In Common Chronic Diseasesmentioning

confidence: 99%

Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases

Ilan

2022

JPM

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Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. This variability is associated with partial or complete loss of drug effectiveness. Regular drug dosing schedules do not comply with physiological variability and contribute to resistance to chronic therapies. In this review, we describe a three-phase platform for overcoming drug resistance: introducing irregularity for improving drug response; establishing a deep learning, closed-loop algorithm for generating a personalized pattern of irregularity for overcoming drug resistance; and upscaling the algorithm by implementing quantified personal variability patterns along with other individualized genetic and proteomic-based ways. The closed-loop, dynamic, subject-tailored variability-based machinery can improve the efficacy of existing therapies in patients with chronic diseases.

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“…In a study by Billiet et al [7], concomitant with an IMM was not favorable with regards to long-term outcomes for patients with CD. In addition, a recent long-term retrospective cohort study revealed that there is no difference in the development of LOR to anti-TNF agents between monotherapy and combination IMM therapy [8].…”

mentioning

confidence: 99%

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

Hong

Park

Yoon

et al. 2021

Korean J Intern Med

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Background/Aims: Combination therapy with immunomodulators (IMMs) was proposed as a strategy to prevent the development of loss of response (LOR) to anti-tumor necrosis factor (TNF) for patients with inflammatory bowel disease (IBD). However, the effect is unclear in patients already exposed to IMMs. The aim of this study was to evaluate whether combination therapy with IMMs is superior to monotherapy for prevention of LOR to anti-TNF. Methods: This was a retrospective study of patients in Seoul National University Bundang Hospital with IBD between January 2009 and October 2018. LOR was defined as clinical deterioration after maintenance of anti-TNF for at least 6 months. We investigated the difference in incidence of LOR to anti-TNF between the monotherapy and combination groups. We additionally assessed factors affecting LOR development to anti-TNF. Results: A total of 116 patients with IBD were included in this study (monotherapy 61 patients; combination 55 patients). Overall, LOR to anti-TNF occurred in 31 patients during the follow-up period. The combination of an anti-TNF agent and IMM showed no significant difference in the incidence of LOR compared to anti-TNF agent monotherapy (hazard ratio [HR], 1.64; 95% confidence interval [CI], 0.786 to 3.148; p = 0.182). Female sex was significantly associated with the development of LOR to anti-TNF (HR, 3.032; 95% CI, 1.467 to 6.268; p = 0.003). Conclusions: Anti-TNF and IMM combination therapy did not prove efficacious in preventing the development of LOR in IBD patients. Female sex was associated with the development of LOR to anti-TNF; further studies are required to confirm these results.

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Immunomodulator use does not prevent first loss of response to anti‐tumour necrosis factor alpha therapy in inflammatory bowel disease: long‐term outcomes in a real‐world cohort

Cited by 7 publications

References 30 publications

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases

Comparison of loss of response between anti-tumor necrosis factor alone and combined use with immunomodulators in patients with inflammatory bowel disease

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