Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn’s Disease

Papamichael, Konstantinos; Rakowsky, Shana; Rivera, Claudio; Cheifetz, Adam S.; Osterman, Mark T.

doi:10.1093/ibd/izy132

Cited by 77 publications

(54 citation statements)

References 24 publications

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“…43 healing. An optimal trough >9.7 µg/mL was observed for patients with CD, 45 and >7.5 µg/mL in a cohort of 56 patients who had moderate to severe UC 46 at the time of infliximab rescue. The discrepancy between the ideal cut-off for CD between the last two studies may relate to varying time-points from drug initiation being used for the more recent study, as opposed to a fixed time point of week 30.…”

Section: Mucosal Healingmentioning

confidence: 89%

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease

Gibson

Ward

Rentsch

et al. 2020

Aliment Pharmacol Ther

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Background Clinical application of therapeutic drug monitoring (TDM) to optimise anti‐TNF therapies in patients with IBD depends upon target ranges. Aims To review methodology used to determine therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab. Methods A systematic review was performed, and relevant literature was summarised and critically examined. Results Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area‐under‐receiver‐operator‐curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end‐points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8‐5.7 µg/mL are reported depending upon end‐points used, with consistent AUROC 0.68‐0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9‐11.8 µg/mL (AUROC 0.66‐0.83) in some studies, but no cut‐off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design. Conclusions Evidence for exposure‐response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.

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Section: Mucosal Healingmentioning

confidence: 89%

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease

Gibson

Ward

Rentsch

et al. 2020

Aliment Pharmacol Ther

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“…During maintenance the minimum trough concentration for adalimumab for patients in Figure 1. (A) Infliximab 13,17,20,[40][41][42][43]45,46,53,55,[59][60][61]64,67 and (B) adalimumab 9,[11][12][13]15,16,[18][19][20][21][22][23]30,31 concentration thresholds associated with biological (based on CRP), biochemical (based on FC), endoscopic, or histologic remission in inflammatory bowel disease. Box whisker plots show the median (solid line within box), interquartile range (upper and lower box boundaries), and lower and upper extreme (whiskers).…”

Section: The Minimum Drug Concentration At Week 4 Formentioning

confidence: 99%

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

Papamichael

Cheifetz

Melmed

et al. 2019

Clinical Gastroenterology and Hepatology

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256

248

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BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 [ strongly disagree and 10 [ strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ‡7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. RESULTS: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. CONCLUSION: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

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“…Most of these data come from observational and/or retrospective studies and suggest that the higher the level of a certain agent, the greater the chance of response. [28][29][30] In contrast, the lower the level is observed, the greater is the chance of nonresponse and/or immunogenicity to biological therapy, mainly driven by the development of antibodies to the drug. 31 There are 2 different strategies for the use of TDM in IBD.…”

Section: Tdm In Ibd: Concepts and Applicationsmentioning

confidence: 99%

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review

2021

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overall CD patients 3 and more than 90% of patients with rectal involvement. 4 The management of PFCD is multidisciplinary, with intensive medical therapy associated to multiple surgical procedures. This usually results in significant physical and psychological impact in patients' lives. There are significant limitations of conventional medical treatment in PFCD (corticosteroids, immunosuppressants, and antibiotics). Fistula healing rates are low with this strategy and recurrence is frequent. 5 Some prospective studies have demonstrated the efficacy of biologics in controlling perianal fistulas in CD. Present et al., 6 in the first randomized controlled study with biologics for the treatment of fistulizing CD, demonstrated the effectiveness of infliximab (IFX) in closing abdominal and perianal fistulas. Sands et al., 7 in the ACCENT 2 study, demonstrated the better efficacy of IFX as compared to

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Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn’s Disease

Abstract: This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.

Cited by 77 publications

References 24 publications

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review

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