Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease

Restellini, Sophie; Afif, Waqqas

doi:10.3390/jcm10061242

Cited by 29 publications

(23 citation statements)

References 73 publications

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“…Endoscopic response is established as a surrogate marker for effective control of CD that predicts a better outcome of the disease [29][30][31]. However, there are a limited number of reports on the association of UST trough levels with endoscopic response in CD patients [32]. As for the ndings in the IM-UNITI maintenance study (mix of 8-or 12-week injections) [17], Adedokun et al reported that the endoscopic remission rate at week 44 was signi cantly higher in patients with a UST trough >0.5 mg/mL than those with ≤0.5 mg/mL, and that the proportion of patients with endoscopic remission reached a plateau at a UST level of 0.5> to ≤1.4 mg/mL.…”

Section: Discussionmentioning

confidence: 99%

Ustekinumab Trough Levels Predicting Laboratory and Endoscopic Remission in Patients with Crohn’s Disease

Hirayana

Morita

Imai

et al. 2021

Preprint

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Backgrounds: Optimal concentration of ustekinumab (UST) predicting endoscopic remission has not been fully investigated in Crohn’s disease (CD). We aimed to identify the optimal UST trough levels predicting clinical, laboratory and endoscopic remission in CD patients. Methods: Twenty-eight patients with CD were enrolled and investigated (27 patients by enteroscopy and 1 by colonoscopy). The endoscopic activity was assessed using the modified Rutgeerts scoring system. Serum UST trough levels and anti-UST antibodies (AUAs) levels were determined by in-house immunoassays. Results: Endoscopic activity was negatively correlated with serum UST trough levels (Spearman’s rank correlation coefficient (ρ) = -0.66, P=0.0001) and serum albumin levels (ρ=-0.60, P=0.0007). The endoscopic activity was positively and significantly correlated with CRP (ρ=0.59, P=0.0009) and ESR (ρ=0.44, P=0.033). There was no significant association between the endoscopic score and AUA levels and/or Crohn’s disease activity index (CDAI). Serum UST trough levels and albumin levels were significantly higher in the endoscopic remission group (scores of 0 and 1) than in the non-endoscopic remission group (UST trough, mean 3.3 vs. 1.8μg/mL). No significant difference was observed in AUAs between the endoscopic remission and non-remission groups. Receiver operation curve (ROC) analysis revealed that the optimal cutoff value of UST trough levels predicting normal CRP and serum albumin levels was 1.7μg/mL for each, and the optimal cutoff value predicting endoscopic remission was 2.0μg/mL (AUC: 0.80, 95%-CI: 0.64-0.96). Conclusion: Endoscopic remission requires higher UST trough levels than those needed to normalize CRP and serum albumin levels.

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Section: Discussionmentioning

confidence: 99%

Ustekinumab Trough Levels Predicting Laboratory and Endoscopic Remission in Patients with Crohn’s Disease

Hirayana

Morita

Imai

et al. 2021

Preprint

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“…In comparison with proactive TDM, the utility of reactive TDM has received a greater consensus in guiding therapy for those patients who lost response and where either dose intensification or change to an alternative therapy may be necessary. The utility of reactive TDM have been extended to recently introduced biologics and oral small molecules[ 25 ].…”

Section: To the Editormentioning

confidence: 99%

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place

Truta¹

2022

WJG

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Therapeutic drug monitoring (TDM) was one of most sought-after objective tools to determine therapeutic efficiency of different biologics and its role in the management of patients with inflammatory bowel disease (IBD) was regarded with great anticipation. But implementation of the TDM in clinical practice was challenged by several factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics. While reactive TDM was embraced in clinical practice as a useful tool in assessing lack of response to therapy, the utility of proactive TDM in managing IBD therapy is still challenged by the lack of consistency between evidence. Described here, there are four groups of IBD patients for whom proactive TDM has the potential to greatly impact their therapeutic outcomes: Patients with perianal Crohn’s disease, patients with severe ulcerative colitis, pregnant women with IBD and children. As the future of IBD management moves towards personalizing treatment, TDM will be an important decision node in a machine learning based algorithm predicting the best strategy to maximize treatment results while minimizing the loss of response to therapy.

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“…Ustekinumab (UST) is a monoclonal antibody against IgG that affects the immunity of IBD patients by binding to the P40 subunit common to interleukin 12 and interleukin 23. According to a review published in 2021, serum UST concentrations are associated with clinical, biochemical, and histological remissions in most clinical trials[ 8 ]. A multicenter crosssectional observational trial based on 110 CD patients concluded that there was no association between short-term clinical outcomes and UST concentrations[ 9 ].…”

Section: To the Editormentioning

confidence: 99%

Therapeutic drug monitoring in inflammatory bowel disease treatments

Wang¹,

Zhao²,

Zheng³

et al. 2022

WJG

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Recently, biological drugs have played a leading role in the treatment of inflammatory bowel disease, and therapeutic drug monitoring (TDM) may be useful in maximizing their effectiveness. TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate. We believe that concentration thresholds should be individualized based on patients’ disease severity, extent and phenotype, and therapeutic purposes should also be considered, with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission. Proactive and reactive TDM can help optimize treatment, especially in patients receiving anti-tumour necrosis factor, and guide dose adjustment or drug conversion with lower cost. TDM is a promising approach to achieve precision medicine and targeted medicine in the future.

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Update on TDM (Therapeutic Drug Monitoring) with Ustekinumab, Vedolizumab and Tofacitinib in Inflammatory Bowel Disease

Cited by 29 publications

References 73 publications

Ustekinumab Trough Levels Predicting Laboratory and Endoscopic Remission in Patients with Crohn’s Disease

Ustekinumab Trough Levels Predicting Laboratory and Endoscopic Remission in Patients with Crohn’s Disease

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place

Therapeutic drug monitoring in inflammatory bowel disease treatments

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