Concentrations of 6-Thioguanine Nucleotide Correlate With Trough Levels of Infliximab in Patients With Inflammatory Bowel Disease on Combination Therapy

Yarur, Andrés; Kubiliun, Maddie; Czul, Frank; Sussman, Daniel A.; Quintero, Maria A.; Jain, Anjali; Drake, Katherine; Hauenstein, Scott; Lockton, Steven; Deshpande, Amar R.; Barkin, Jamie S.; Singh, Sharat; Abreu, María T.

doi:10.1016/j.cgh.2014.12.026

Cited by 139 publications

(107 citation statements)

References 30 publications

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“…sufficient to obtain a favourable and sustained pharmacokinetics of IFX as previously described by Yarur et al 5 In this latter work, 6 are improved by lowering the dose of AZA, which is crucial to achieve adherence to treatment.…”

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confidence: 60%

Letter: thiopurines ‐ is less really more? Authors’ reply

Roblin

Paul

Nancey³

et al. 2017

Aliment Pharmacol Ther

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digestive intolerance and myelotoxicity) 6 are improved by lowering the dose of AZA, which is crucial to achieve adherence to treatment.Regarding severe medium-term risks (lymphomas, skin cancers), no data in IBD can be used to correlate 6-TGN levels and side effects.However, data in children with acute leukaemia or in patients with renal grafts and nonmelanoma skin cancer showed that elevated 6-TGN levels were an independent risk factor for these complications. 7,8 In any case, using a lower dose of a treatment resulting in the same efficacy than the full dose is unlikely to increase the risk of its side effects. ACKNOWLEDGEMENTSThe authors' declarations of personal and financial interests are unchanged from those in the original article.

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confidence: 60%

Letter: thiopurines ‐ is less really more? Authors’ reply

Roblin

Paul

Nancey³

et al. 2017

Aliment Pharmacol Ther

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“…6-TG levels less than 125 pmol/8×10 8 RBCs are associated with higher anti-infliximab antibodies and higher 6-TG levels are associated with clinical remission [Osterman et al 2006;Yarur et al 2015].…”

Section: Optimization Of Immunomodulator Dosingmentioning

confidence: 99%

“…In addition, patients on infliximab monotherapy have lower infliximab drug levels than patients on combination therapy with azathioprine. Yarur and colleagues showed that a higher level of serum 6-thioguanine nucleotides positively correlated with serum infliximab level (correlation coefficient 0.52) [Yarur et al 2015].…”

Section: Combination Therapymentioning

confidence: 99%

“…For thiopurine immunomodulators, patients with a 6-thioguanine (6-TG) nucleotide level of less than 125 pmol/8×10 8 red blood cells (RBCs) have a significantly higher likelihood of having detectable anti-infliximab antibodies (odds ratio 13) [Yarur et al 2015]. A methotrexate dose of 15 mg or more weekly in combination with an anti-TNFα biologic was associated with longer duration of clinical remission in a retrospective review of patients with inflammatory bowel disease (IBD) at our institution [Colman and Rubin, 2015].…”

Section: Combination Therapymentioning

confidence: 99%

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Current approaches for optimizing the benefit of biologic therapy in ulcerative colitis

Sofia

Rubin

2016

Therap Adv Gastroenterol

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As biologic-based medication options for ulcerative colitis expand, our understanding of their optimal use in clinical practice is advancing as well. The appropriate use of combination therapy with immunomodulators can reduce the immunogenicity of biologic agents and raise serum drug levels of the biologic. A treat-to-target strategy with objective assessments of disease activity clearly defines the goals of biologic drug treatment. Mucosal healing is an evolving treatment goal and is associated with long-term remission and reduced incidence of colectomy. Furthermore, regular reassessments and therapeutic drug monitoring can allow clinicians to make evidence-based changes in therapy. Biologic drug deescalation or re-initiation are less well developed topics, but are emerging areas of study. We review the evidence underlying these advances and a modern approach to the use of biologic therapy in ulcerative colitis.

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“…This is relevant because of recent reports suggesting that lower doses and 6-TGN concentrations were associated with prevention of immunogenicity. 10 Furthermore, as discussed by the authors, utilisation of drug-tolerant ADA assays may reveal patient populations that may benefit from this strategy as well. Despite its efficacy, safety concerns regarding combination therapy still exist.…”

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confidence: 99%