Loss of Infliximab Into Feces Is Associated With Lack of Response to Therapy in Patients With Severe Ulcerative Colitis

Brandse, Johannan F.; Brink, Gijs R. van den; Wildenberg, Manon E.; Kleij, Desirée van der; Rispens, Theo; Jansen, Jeroen M.; Mathôt, Ron A. A.; Ponsioen, Cyriel Y.; Löwenberg, Mark; D’Haens, Geert R.

doi:10.1053/j.gastro.2015.04.016

Cited by 345 publications

(267 citation statements)

References 31 publications

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“…Antibody formation against anti‐TNFα can lead to reduced trough levels of anti‐TNFα, which can lead to increased disease activity 5. In addition, there is evidence particularly for acute severe ulcerative colitis (UC) that the inflamed, ulcerated gut can act as a sink for anti‐TNFα, with greater loss of anti‐TNFα in stool and subsequent suboptimal response 6, 7…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…A high inflammatory burden also contributes to low serum drug levels [29,30]. Drug clearance is influenced by high tissue TNFa concentrations, low serum albumin concentration, and infliximab loss into the stool [31][32][33][34]. In response to these findings, proactive drug monitoring became a subject of intense investigation; for example, accelerated infliximab dosing for acute, severe ulcerative colitis can reduce short-term colectomy rates [35].…”

Section: Development Of Infliximabmentioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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“…Maintenance therapy aft er induction with IFX is now the standard of care and concurrent thiopurine therapy has been shown to enhance remission rates ( 9 ). In SR-ASUC, both a severely infl amed colon and hypoalbuminemia lower circulating IFX levels ( 10,11 ). Hence, clinicians have initiated unproven approaches to IFX use in SR-ASUC such as initiating doses with 10 mg/kg or repeated dosing over a short period if there is an inadequate response to the initial dose.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

Yes, We Are Still Talking about Cylosporin vs. Infliximab in Steroid Resistant Acute Severe Ulcerative Colitis

Bernstein

Kornbluth

2017

American Journal of Gastroenterology

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The Spanish IBD Registry (ENEIDA) is reporting in this issue of the Journal on a retrospective assessment of outcomes of cyclosporine use and infl iximab use to treat steroid refractory acute severe ulcerative colitis (SR-ASUC) between 1989 and 2013. Overall, they found similar outcomes in terms of 3 month and 1 year colectomy rates. Serious adverse events were lower in cyclosporine users. While this study does not meet the standard of a prospective randomized controlled trial, it does remind us that cyclosporine can be effective in (SR-ASUC) and should be considered in those who have already failed antibody to tumor necrosis factor therapy or as a bridge to immunomodulators that have a slower onset of action.

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Loss of Infliximab Into Feces Is Associated With Lack of Response to Therapy in Patients With Severe Ulcerative Colitis

Cited by 345 publications

References 31 publications

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

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

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Yes, We Are Still Talking about Cylosporin vs. Infliximab in Steroid Resistant Acute Severe Ulcerative Colitis

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