Anti-TNF Re-induction Is as Effective, Simpler, and Cheaper Compared With Dose Interval Shortening for Secondary Loss of Response in Crohn’s Disease

Srinivasan, Ashish; Vasudevan, Abhinav; McFarlane, Anne; Sparrow, Miles P.; Gibson, Peter R.; Langenberg, Daniel R. van

doi:10.1093/ecco-jcc/jjx144

Cited by 25 publications

(50 citation statements)

References 21 publications

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“…Despite ustekinumab’s efficacy in Crohn’s disease (CD), a subset of ustekinumab‐treated patients develop primary or secondary nonresponse that may respond to dose intensification 2‐5 . Unlike other biologic agents, the comparative effectiveness of ustekinumab dose‐intensification strategies such as re‐induction and/or dose interval shortening, has not been reported 6 …”

mentioning

confidence: 99%

Letter: ustekinumab dose intensification for loss of response—should we re‐induce before shortening the dose interval?

Srinivasan

Cruz

Langenberg

2020

Aliment Pharmacol Ther

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mentioning

confidence: 99%

Letter: ustekinumab dose intensification for loss of response—should we re‐induce before shortening the dose interval?

Srinivasan

Cruz

Langenberg

2020

Aliment Pharmacol Ther

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“…One retrospective study 57 (n = 80) compared anti‐TNF reinduction to shortening the dosing interval in a cohort with complex CD (91% stricturing or penetrating) and secondary loss of response. There was no significant difference in the rates of treatment failure within 12 months of reinduction compared to dose escalation (24% vs 15%, P = 0.27) 57 . However, beyond 24 months, rates of treatment failure were higher in the reinduction group compared to the dose escalation group, leading to a higher overall rate of treatment failure after reinduction over the course of the study (48% vs 24%, P = 0.02) 57 …”

Section: Resultsmentioning

confidence: 99%

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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“…Re-induction is an effective strategy in LOR (35). Dose intensification was proposed as a means of overcoming LOR in IBD.…”

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

confidence: 99%

“…Patients and disease phenotypes: Factors predictive of longer time to failure include obesity, smoking, higher baseline serum albumin, male sex, and thiopurine co-therapy. Higher baseline fecal calprotectin is associated with shorter time to failure (21, 34, 35). Elevated body mass index (BMI) is associated with poorer response to IFX and correlates with higher drug levels, but not a higher response rate, suggesting that circulating drug levels do not correlate with tissue levels (36).…”

Section: Difficulties In Predicting Lor To Anti-tnfs In Ra and Ibd Prmentioning

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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Anti-TNF Re-induction Is as Effective, Simpler, and Cheaper Compared With Dose Interval Shortening for Secondary Loss of Response in Crohn’s Disease

Abstract: In patients with CD who develop secondary LOR, re-induction may represent an effective and less expensive first-line strategy, reserving dose intensification strategies such as DIS for non-responders.

Cited by 25 publications

References 21 publications

Letter: ustekinumab dose intensification for loss of response—should we re‐induce before shortening the dose interval?

Letter: ustekinumab dose intensification for loss of response—should we re‐induce before shortening the dose interval?

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

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

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