Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

Roblin, Xavier; Marotte, Hubert; Rinaudo, M.; Tedesco, Émilie Del; Moreau, A; Phelip, Jean Marc; Genin, Christian; Peyrin–Biroulet, Laurent; Paul, Stéphane

doi:10.1016/j.cgh.2013.07.010

Cited by 252 publications

(195 citation statements)

References 14 publications

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“…A recent French study evaluated the correlation between ADA levels and mucosal healing, demonstrating that a level of up to 4.9 μg/ml was found to be associated with an absence of mucosal healing with a positive predictive value of 88% and negative predictive value of 51% [Roblin et al 2014]. In a recent study from Israel, a cutoff drug level of 5.85 µg/ml yielded optimal sensitivity, specificity and a positive likelihood ratio for prediction of clinical response [Mazor et al 2013].…”

Section: Immunopharmacological Predictorsmentioning

confidence: 99%

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

Kopylov

Seidman

2016

Therap Adv Gastroenterol

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Monoclonal antibodies to tumor necrosis factor (TNF) have become a mainstay of the therapeutic armamentarium in inflammatory bowel disease (IBD) over the last 15 years. Although highly effective, primary and secondary nonresponse are common and associated with poor clinical outcomes and significant costs. Multiple clinical, genetic and immunopharmacological factors may impact the response to anti-TNFs. Early stratification of IBD patients by the expected risk of therapeutic failure during the induction and maintenance phases of treatment may allow for treatment optimization and potentially optimal short-and long-term outcomes. The aim of this review is to summarize the current data concerning the potential predictors of therapeutic success and failure of anti-TNFs in IBD.

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Section: Immunopharmacological Predictorsmentioning

confidence: 99%

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

Kopylov

Seidman

2016

Therap Adv Gastroenterol

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“…Several further studies also demonstrated that patients who have detectable trough infl iximab levels are likely to remain in remission compared with those with undetectable trough infl iximab levels ( 58,73,74 ). Similar studies have demonstrated the predictive value of adalimumab drug levels ( 75 ).…”

Section: Anti-tnf and Anti-integrin Therapymentioning

confidence: 68%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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“…Seow and colleagues similarly showed that the presence of a detectable infliximab trough was significantly associated with higher likelihood of remission and reduced risk for colectomy [Seow et al 2010]. Similarly, Roblin and colleagues found that higher trough levels of adalimumab were significantly associated with a higher likelihood of mucosal healing in a cohort of patients with UC and Crohn's disease [Roblin et al 2014]. …”

Section: Serum Drug Levels Optimal Serum Targetsmentioning

confidence: 91%

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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Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

Cited by 252 publications

References 14 publications

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

Predicting durable response or resistance to antitumor necrosis factor therapy in inflammatory bowel disease

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

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

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