Association Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease

Colombel, Jean–Frédéric; Sandborn, William J.; Allez, Matthieu; Dupas, Jean‐Louis; Dewit, Olivier; D’Haens, Geert R.; Bouhnik, Yoram; Parker, Gerald W.; Pierre-Louis, Bosny; Hébuterne, Xavier

doi:10.1016/j.cgh.2013.10.025

Cited by 111 publications

(56 citation statements)

References 24 publications

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“…When considering TNF-antagonists, mucosal healing rates at 12 months with adalimumab and certolizumab have been reported to be in the range of 20-25%, with endoscopic remission being achieved in up to 50% of patients ( 23,24 ). With infl iximab, ~30% of individuals achieved mucosal healing by 6 months with rates increasing to 45% when using concomitant immunosuppressive therapy ( 4,25 ).…”

Section: Safetymentioning

confidence: 95%

The Real-World Effectiveness and Safety of Vedolizumab for Moderate–Severe Crohn’s Disease: Results From the US VICTORY Consortium

Dulai

Singh

Jiang

et al. 2016

American Journal of Gastroenterology

276

237

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Section: Safetymentioning

confidence: 95%

The Real-World Effectiveness and Safety of Vedolizumab for Moderate–Severe Crohn’s Disease: Results From the US VICTORY Consortium

Dulai

Singh

Jiang

et al. 2016

American Journal of Gastroenterology

276

237

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“…Maser et al [49] described the association of detectable infliximab trough levels with improved clinical, endoscopic and biomarker outcomes in CD patients. Subsequently, multiple studies have confirmed the positive association between anti-TNF trough levels (infliximab [5] , adalimumab [50] and certolizumab pegol [51] ) and efficacy outcomes as well as the negative association between ADA and response in IBD patients. Colectomy rates among UC patients are increased significantly in patients having undetectable trough drug levels during maintenance therapy with infliximab [5] .…”

Section: Clearancementioning

confidence: 98%

The Pharmacokinetics of Biologics: A Primer

Mould¹

2015

Dig Dis

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Monoclonal antibodies (MAbs) exhibit complex pharmacokinetics (PK) and pharmacodynamics (PD, response) against tumor necrosis factor (TNF). Many factors impact anti-TNF MAb PK, altering MAb clearance and therefore the half-life: albumin, weight (particularly, obesity), disease (severity, stage and co-morbidities) and concomitant administration of immunosuppressants (e.g. methotrexate). These factors can alter MAb exposure, impacting on the likelihood of clinical response. Formation of anti-drug antibodies (ADAs) is another potential factor that can affect MAb PK. Factors impacting the likelihood of developing ADA are classified as patient-related (concomitant immunosuppressants, prior ADA against other anti-TNF MAb) or product-related (structure, manufacturing process, aggregate formation, route of administration and dosing regimen). Repeated episodic exposure can induce ADAs, shortening the effective treatment interval. Avoiding intervals where anti-TNF MAbs are non-measurable is important for efficacy and may delay onset of ADAs. Thus, patients whose factors predispose them to having faster clearance (or short half-life) such as severe disease, low albumin or high body weight may need shorter dose intervals to reduce the likelihood of intermittent exposure. ADAs can have no effect or can impact efficacy through MAb binding, thus inhibiting its function or potentially causing hypersensitivity reactions (PD). ADA can also increase MAb clearance (PK). Because of their impact on MAb clearance, ADAs have been linked to lower serum drug concentrations, potentially negatively impacting clinical response. ADAs have been reported for biologics in most therapeutic areas. ADAs are well documented in clinical studies due to the Food and Drug Administration and the European Medicines Agency recommendations regarding testing and impact of immunogenicity. Lastly, the dose metrics (e.g. mg vs. mg/kg) can cause issues as well. MAbs such as infliximab are dosed on a mg/kg basis, which commonly results in low concentrations in patients with low body weight. Conversely MAbs such as adalimumab are administered as a flat (mg) dose, which can result in low concentrations in high weight patients.

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“…Multiple studies have confi rmed a correlation between clinical response and trough serum levels of anti-TNF medications [13][14][15][16][17]. Moreover, such correlation was recently established not only for clinical response but for endoscopic outcomes (mucosal healing) and decline of infl ammation markers [18][19][20][21].…”

Section: Risk Factors For Secondary Lormentioning

confidence: 97%

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

2017

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Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn's disease and ulcerative colitis. A signifi cant proportion of patients loses response to these agents or develops adverse eff ects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients. Th is review summarizes the current knowledge on the clinical implications of therapeutic drug monitoring in infl ammatory bowel disease patients treated with TNF-α inhibitors and thiopurines.

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Association Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease

Cited by 111 publications

References 24 publications

The Real-World Effectiveness and Safety of Vedolizumab for Moderate–Severe Crohn’s Disease: Results From the US VICTORY Consortium

The Real-World Effectiveness and Safety of Vedolizumab for Moderate–Severe Crohn’s Disease: Results From the US VICTORY Consortium

The Pharmacokinetics of Biologics: A Primer

Therapeutic Drug Monitoring in Inflammatory Bowel Disease

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