The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab

Ungar, Bella; Chowers, Yehuda; Yavzori, Miri; Picard, Orit; Fudim, Ella; Har-Noy, Ofir; Kopylov, Uri; Eliakim, Rami; Ben‐Horin, Shomron

doi:10.1136/gutjnl-2013-305259

Cited by 274 publications

(197 citation statements)

References 31 publications

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“…Anti‐TNFα trough and antibodies were measured at the end of induction therapy between weeks 10 and 12 as follows: Drug levels were assayed using a protocol adapted from Ungar et al 14. Briefly, ELISA plates (Thermo Scientific NUNC, Basingstoke, UK) were coated with 500 ng/mL recombinant human TNFα (Peprotech, London, UK) overnight at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Positive relationship between infliximab and adalimumab trough levels at completion of induction therapy with clinical response rates, at a tertiary referral center

et al. 2017

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Background and AimAnti‐tumor necrosis factor alpha (TNFα) therapies have improved outcomes for patients with inflammatory bowel disease. The aim of this study was to explore the relationship between infliximab (IFX) and adalimumab (ADL) trough and antibody levels with clinical response rates at the end of induction.MethodsThis was a prospective, single‐center study. Patients were recruited from July 2015 to August 2016. Inclusion criteria were all inflammatory bowel disease patients older than 17 years who started treatment with IFX or ADL. Baseline clinical disease activity indexes were performed. Clinical response was defined as HBI ≤3 or partial Mayo score ≤4% or <30% reduction from baseline. Anti‐TNFα trough and antibody levels were measured using standard ELISA techniques.ResultsThirty‐five patients were recruited, of whom 23 had Crohn's disease and 12 had ulcerative colitis. Eighteen were treated with ADL and 17 with IFX. The mean age of the cohort was 40.3 years, 62.9% were females, 34.3% were on concomitant thiopurines, and 25.7% had prior anti‐TNFα exposure. Overall response rate was 51.4%, 33.3% for ADL and 70.6% for IFX.Mean trough levels were 12.5 μg/mL for IFX and 4.4 μg/mL for ADL. There was a clear link between higher anti‐TNFα trough levels at the end of induction with clinical response rates. For IFX, mean trough level was 16.4 μg/mL for responders versus 5.3 μg/mL for non‐responders (P = 0.026). Area under the curve for association of IFX level at induction with clinical response was 0.864 (P = 0.0001). Similar link was present between higher ADL levels with clinical response, although not statistically significant.ConclusionHigher trough levels at the end of induction are associated with improved response. Ongoing work will define optimal targets at this key timeframe.

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Section: Methodsmentioning

confidence: 99%

“…Anti‐drug antibody levels were assayed using a protocol adapted from Ungar et al 14. ELISA plates (Thermo Scientific NUNC) were coated overnight with 500 ng/mL TNFα (Peprotech) as outlined above.…”

Section: Methodsmentioning

confidence: 99%

Positive relationship between infliximab and adalimumab trough levels at completion of induction therapy with clinical response rates, at a tertiary referral center

et al. 2017

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“…Moreover, serum anti-TNF levels and ATI most likely represent a continuous process, which may frequently start with low-titer antibodies that do not hamper the serum levels of the drug signifi cantly, progressing to hightiter antibodies leading to a complete elimination of the drug. Frequently detection of ATI will precede the development of LOR by several weeks, or alternatively, will be detected aft er LOR has developed [31]. Moreover, transient (appearing on a single measurement without recurrence) ATI are a frequent phenomenon, described in up to 28% of patients [32].…”

Section: Antibodiesmentioning

confidence: 99%

“…Moreover, transient (appearing on a single measurement without recurrence) ATI are a frequent phenomenon, described in up to 28% of patients [32]. In contrast to persistent ATI that rarely (<10%) appear aft er 1 year of treatment, these transient antibodies may be detected at any point during the treatment without a signifi cant impact on LORfree survival [31]. Th e risk of ATI formation has been repeatedly demonstrated to be lower in patients receiving concomitant immunomodulatory therapy [11,12,30].…”

Section: Antibodiesmentioning

confidence: 99%

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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“…Applying an immunomodulator to salvage anti-TNF therapy in patients with LOR has been reported previously for both infliximab and adalimumab, 7,8 with up to 48%…”

mentioning

confidence: 99%