High-Dose Infliximab Therapy in Crohn’s Disease: Clinical Experience, Safety,
          and Efficacy

Hendler, Steven; Cohen, Benjamin L.; Colombel, Jean–Frédéric; Sands, Bruce E.; Mayer, Lloyd; Agarwal, Shradha

doi:10.1093/ecco-jcc/jju026

Cited by 49 publications

(78 citation statements)

References 26 publications

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“…In one study, the mean duration of persistence with aTNF agents progressively decreased for each subsequent line of therapy (mean: 21.5, 17.4 and 13.2 months with first‐, second‐ and third‐line therapy, respectively) . As expected, one study found that patients who showed early response to treatment (high‐dose IFX) had a statistically longer duration of treatment compared with those who had no response ( P = 0.0006; retrospective single‐centre chart review, 2010‐2012) …”

Section: Resultsmentioning

confidence: 73%

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Real‐world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review

et al. 2019

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Summary What is known and objective The application of biologics to treat inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is well established. Our aim was to characterize the most recent five years of data on rates of adherence, persistence, switching and dose escalations with biologics used to treat IBD in the United States. Methods We systematically reviewed electronic databases MEDLINE, MEDLINE In‐Process, EMBASE and Cochrane Library for 2012‐2017 as well as conference proceedings for 2016‐2017 published in English. Results and discussion Of 449 records identified, 41 met all screening criteria. Published studies varied greatly in methodology, data sources, population studied, follow‐up time and endpoint definitions, preventing meaningful comparisons across studies. Based on studies using a medication possession rate threshold of <80% or <86%, 38%‐77% of patients were found non‐adherent to biologics. Discontinuation within the first 3 months occurred in 0%‐25% of patients in six studies; 7%‐65% discontinued by 12 months in 13 studies. Among all patients who initiated an index biologic, the switch rate to another biologic ranged from 4.5% to 20% in 6 studies. Dose escalations were reported in only four studies; 8%‐35% of patients had their dose escalated within the first year of therapy. What is new and conclusion This study demonstrates variability in study design and methodology to assess adherence, persistence, switching and dose escalation with biologics among adults with IBD in the United States. Our findings suggest that real‐world biologic use may be suboptimal and indicate new therapies and/or additional patient support may be needed.

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Section: Resultsmentioning

confidence: 73%

“…The main reasons for discontinuation were lack or loss of response, followed by adverse events . The main reasons for discontinuation differed by line of therapy.…”

Section: Resultsmentioning

confidence: 99%

Real‐world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review

et al. 2019

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“…(7–12) Dose optimization including dose escalation based on trough concentration monitoring has proved beneficial. (10,13,14) In children with CD, trough concentrations achieved after standard infliximab maintenance dosing are not well characterized. Important predictors of infliximab drug clearance in children with CD have been identified with weight and serum albumin having the largest influence.…”

Section: Introductionmentioning

confidence: 99%

Infliximab Dosing Strategies and Predicted Trough Exposure in Children With Crohn Disease

Frymoyer

Piester

Park

2016

J. pediatr. gastroenterol. nutr.

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Objectives Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn’s disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 μg/ml. Methods A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy. Results Based on the index case of a 10 year old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (IQR) simulated infliximab trough concentration at week 14 was 1.3 (0.5–2.7) μg/ml, and 2.4 (1.0–4.8) μg/ml for albumin levels of 3 and 4 g/dl, respectively. Among 1000 simulated children in the model, trough concentration >3 μg/ml at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dl, respectively. Conclusions Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy.

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“…However, there are only limited data regarding the potential association of supra-therapeutic drug concentrations with increased toxicity or adverse events. Preliminary data suggest that high infliximab dosing [between 10 mg and 22.5 mg/kg every 4 to 7 weeks] may be associated with serious infections, 18 whereas higher anti-TNF concentrations [infliximab >5 µg/ml and adalimumab > 6.6 µg/ml] are associated with an impaired quality of life (based on the Inflammatory Bowel Disease Questionnaire [IBDQ]), particularly regarding systemic symptoms and emotional status. 19 Finally, another study showed that higher preoperative serum anti-TNF drug levels are associated with higher rates of adverse postoperative outcomes in CD, such as postoperative morbidity, infectious complications, or hospital re-admissions.…”

mentioning

confidence: 99%

Higher Adalimumab Drug Levels Are Associated with Mucosal Healing in Patients with Crohn’s Disease

Papamichael

Cheifetz

2016

ECCOJC

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Anti-tumour necrosis factor [TNF] therapy has revolutionised the treatment of patients with inflammatory bowel disease [IBD], both Crohn's disease [CD] and ulcerative colitis [UC]. In addition to steroid-free clinical remission, objective therapeutic outcomes, such as mucosal healing, are emerging as goals of care in IBD, leading to the concept of a treat-to-target therapeutic approach.1 Mucosal healing is associated with favourable therapeutic outcomes in IBD including lower relapse, hospitalisation and surgery rates. Exposure-response studies of anti-TNF therapy, based on therapeutic drug monitoring [TDM], show that favourable therapeutic outcomes, such as mucosal healing, are associated with high serum drug concentrations and undetectable anti-drug antibodies. 3,4,5,6,7,8,9 However, the majority of these studies, as well as two recently published meta-analyses, refer mainly to infliximab. 3,4,5,6,7,8,9,10,11 . Only limited data are available regarding the relationship of adalimumab concentrations, and antibodies to adalimumab [ATA], with favourable clinical outcomes and specifically with mucosal healing. 4,5,6,7 Based on these preliminary data, higher adalimumab levels and absence of ATA during maintenance therapy are associated with mucosal healing in IBD [ Tables 1 and 2 with a combined accuracy of 81.7% when based on the previously described cut-off of 4.9 μg/ml. 4,7 This, along with data from other recent studies, suggests that a threshold of 4.9 μg/ml may not be sufficient to achieve mucosal healing or deep remission. 5,6,7

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High-Dose Infliximab Therapy in Crohn’s Disease: Clinical Experience, Safety, and Efficacy

Cited by 49 publications

References 26 publications

Real‐world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review

Real‐world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review

Infliximab Dosing Strategies and Predicted Trough Exposure in Children With Crohn Disease

Higher Adalimumab Drug Levels Are Associated with Mucosal Healing in Patients with Crohn’s Disease

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