788 Higher 6-Thioguanine Nucleotide Concentrations Are Associated With Higher Trough Levels of Infliximab in Patients on Combination Therapy

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

doi:10.1016/s0016-5085(14)60476-5

Cited by 3 publications

(4 citation statements)

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“…The drug metabolism of patients with lower TPMT activity is shifted toward an increased production of active compounds (6-TGN), responsible for the therapeutic effects of the drug. 20 Among patients with early rheumatoid arthritis, a recent prospective randomized controlled trial performed in 395 patients assigned patient to receive adalimumab in association with methotrexate at 2.5, 5, 10, or 20 mg. 21 Patients with low dose of methotrexate at 2.5 and 5 mg developed more antibodies toward infliximab (ATI) and had lower trough concentrations as compared with patients with higher dose of 10 and 30 mg of methotrexate. We were not able to assess this relationship in the SONIC trial because 6-TGN concentrations were not measured.…”

Section: Discussionmentioning

confidence: 99%

Change in Erythrocyte Mean Corpuscular Volume During Combination Therapy with Azathioprine and Infliximab Is Associated with Mucosal Healing

Bouguen

Sninsky

Tang

et al. 2015

Inflammatory Bowel Diseases

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Section: Discussionmentioning

confidence: 99%

Change in Erythrocyte Mean Corpuscular Volume During Combination Therapy with Azathioprine and Infliximab Is Associated with Mucosal Healing

Bouguen

Sninsky

Tang

et al. 2015

Inflammatory Bowel Diseases

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“…AZA and 6MP when used in combination with anti-TNF have been found to consistently decrease anti-TNF antibody formation and increase drug levels [Dulai et al 2014]. As monotherapy, 6-MP has been found to have its optimal therapeutic effect in achieving clinical remission at a cutoff concentration of 230-260 pmol/8 × 10 8 red blood cells (RBC) and is thus the suggested target level, rather than the former weight-based dosing [Dubinsky et al 2000;Osterman et al 2006] However, a recent study by Yaryr and colleagues found that a cutoff 6-TG level of 125 pmol/8 × 10 8 RBC may be sufficient at promoting higher anti-TNF levels, and this lower target may maximize infliximab levels while minimizing toxicity in IBD patients on combination therapy [Yaryr et al 2014]. It is possible that the addition of thiopurines may deplete antigen-specific T cells, or drug-specific memory clones, thus reducing the titers of ATIs and ADAs [Yaryr et al 2014].…”

Section: Reducing Immunogenicity With Combination Therapymentioning

confidence: 99%

“…2000; Osterman et al . 2006] However, a recent study by Yaryr and colleagues found that a cutoff 6-TG level of 125 pmol/8 × 10 8 RBC may be sufficient at promoting higher anti-TNF levels, and this lower target may maximize infliximab levels while minimizing toxicity in IBD patients on combination therapy [Yaryr et al . 2014].…”

Section: Reducing Immunogenicity With Combination Therapymentioning

confidence: 99%

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Optimizing the use of anti-tumor necrosis factor in the management of patients with Crohn’s disease

Nguyen

Flores

Sassi

et al. 2015

Therapeutic Advances in Chronic Disease

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Abstract:Since the approval of the first anti-tumor necrosis factor (anti-TNF) therapy in late 1998, the treatment for Crohn's disease (CD) has been revolutionized. Anti-TNF therapy has been consistently shown in numerous clinical trials to be effective for patients with more aggressive perianal, internal penetrating, and fistulizing CD. However, the loss of clinical remission is frequent and only one-third of patients remain in clinical remission at 1 year. The pharmacokinetics of anti-TNF is highly variable among patients and could be influenced by many factors including serum albumin, gender, body weight, systemic inflammation and route of administration. The main factor impacting anti-TNF pharmacokinetics and efficacy is the development of immunogenicity where antidrug antibodies accelerate anti-TNF drug clearance. In this review paper, we evaluate the role of combination therapy with anti-TNF drugs and immunomodulators, the role of therapeutic drug monitoring, and strategies to recapture loss of clinical response in order to improve both short-and long-term outcomes in CD patients.

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Therapeutic Drug Monitoring of Anti-tumor Necrosis Factor Agents in Patients with Inflammatory Bowel Diseases

Yarur

Rubin

2015

Inflammatory Bowel Diseases

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Anti-tumor necrosis factor (TNF) agents have radically changed the treatment of inflammatory bowel diseases. Although a significant amount of patients respond to therapy, others experience only a partial response or do not benefit at all. Although, in some cases, the mechanistic action of the anti-TNF therapy may explain such findings, we have now learned that many patients may instead suffer from inadequate dosing and drug exposure. Such heterogeneity in how patients respond to therapy may be explained by multiple pharmacodynamic variables, such as factors that alter drug clearance, including the level of systemic inflammation, the presence of antidrug antibodies, and concomitant use of immunomodulators. Multiple studies have found that low-serum anti-TNF levels are associated with active disease and that adjusting the dose in these cases may offer a therapeutic benefit. In this review, we discuss the most recent evidence on therapeutic drug monitoring in patients with inflammatory bowel disease receiving anti-TNF biological therapies.

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788 Higher 6-Thioguanine Nucleotide Concentrations Are Associated With Higher Trough Levels of Infliximab in Patients on Combination Therapy

Cited by 3 publications

References 0 publications

Change in Erythrocyte Mean Corpuscular Volume During Combination Therapy with Azathioprine and Infliximab Is Associated with Mucosal Healing

Change in Erythrocyte Mean Corpuscular Volume During Combination Therapy with Azathioprine and Infliximab Is Associated with Mucosal Healing

Optimizing the use of anti-tumor necrosis factor in the management of patients with Crohn’s disease

Therapeutic Drug Monitoring of Anti-tumor Necrosis Factor Agents in Patients with Inflammatory Bowel Diseases

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