Systematic Review and Meta-Analysis: Serum Infliximab Levels During Maintenance Therapy and Outcomes in Inflammatory Bowel Disease

Moore, Clare; Corbett, Gillian; Moss, Alan C.

doi:10.1093/ecco-jcc/jjw007

Cited by 105 publications

(63 citation statements)

References 38 publications

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“…Studies have found that responders have higher infliximab levels than nonresponders . Several have defined an infliximab therapeutic cut‐off or range that is associated with a specific endpoint . In a retrospective study of secondary loss‐of‐response in IBD, a pre‐dose intensification infliximab trough of ≥3.4 μg/mL was 90% specific for failure to recapture response .…”

Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

245

207

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Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

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Section: Resultsmentioning

confidence: 99%

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Mitrev¹,

Casteele

Seow³

et al. 2017

Aliment Pharmacol Ther

245

207

View full text Add to dashboard Cite

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“…The majority of the published literature is with IFX and in general it is accepted (depending on the assay used as a reference) that a trough level of >3 μg/mL is associated with response in patients with luminal CD 35. However, a debate arises whether patients with PFCD would benefit from higher drug levels.…”

Section: Conventional Non-biologic Medical Therapy Biologics and Permentioning

confidence: 99%

Modern management of perianal fistulas in Crohn’s disease: future directions

Kotze

Shen

Lightner

et al. 2018

Gut

142

104

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Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

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“…These patients typically have low infliximab trough levels, suggesting a pharmacokinetic issue . Conversely, high trough levels have been associated with clinical and biochemical remission, C‐reactive protein and faecal calprotectin normalisation, mucosal healing and even fistula healing . Consequently, different strategies have been developed to tackle low trough levels, such as adding azathioprine to infliximab during the most vulnerable period of 6‐12 months after its initiation, a strategy known as combination treatment .…”

Section: Introductionmentioning

confidence: 99%

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

Drobne

Kurent

Golob

et al. 2019

Aliment Pharmacol Ther

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Background: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a potentially safer but under-studied alternative.Aim: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies.Methods: We studied the clinical success and infliximab consumption with both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation.Results: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no significant differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions:In this study, optimised infliximab monotherapy was as clinically effective as combination therapy, but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.

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Systematic Review and Meta-Analysis: Serum Infliximab Levels During Maintenance Therapy and Outcomes in Inflammatory Bowel Disease

Abstract: There is a significant difference between serum infliximab levels in patients with IBD in remission, compared with those who relapse. A trough threshold during maintenance > 2 µg/ml is associated with a greater probability of clinical remission and mucosal healing.

Cited by 105 publications

References 38 publications

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Review article: consensus statements on therapeutic drug monitoring of anti‐tumour necrosis factor therapy in inflammatory bowel diseases

Modern management of perianal fistulas in Crohn’s disease: future directions

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease

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