Outcomes After Primary Infliximab Treatment Failure in Inflammatory Bowel Disease

Buhl, Sine; Steenholdt, Casper; Rasmussen, Merete; Borghede, Märta K.; Brynskov, Jørn; Thomsen, Ole Østergaard; Ainsworth, Mark

doi:10.1097/mib.0000000000001117

Cited by 21 publications

(9 citation statements)

References 40 publications

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“…Failures to biologicals are well-known hard-to-treat patients, and treatment responses to any biological in this cohort are expected to be low. 3 54 Along with a low sample size, this might explain the rather high rate of non-responders in the present study. In patients showing partial response to vedolizumab induction therapy, a shortened dosing interval of one or several doses was initiated to ensure adequate drug levels, although these were not measured.…”

Section: Discussionmentioning

confidence: 75%

Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD

Soendergaard

Seidelin

Steenholdt

et al. 2018

BMJ Open Gastroenterol

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ObjectivesCharacterise the circulating inflammatory cytokine pattern among patients failing consecutive anti-tumour necrosis factor (anti-TNF) and anti-integrin treatments to identify predictors of response.MethodsA retrospective single-centre cohort study of 28 patients with inflammatory bowel disease (IBD) receiving anti-integrin therapy (vedolizumab) subsequent to the failure of anti-TNF treatment was conducted. Blood samples were obtained immediately prior to initiation of vedolizumab therapy, and the response to treatment was evaluated after completion of the 14-week induction regimen. Multiplex ELISA was applied to quantify 47 preselected plasma proteins based on their putative involvement in the inflammatory process in IBD.ResultsAnti-TNF and vedolizumab non-responders (n=20) had significantly higher levels of circulating interleukin (IL)-6 than anti-TNF non-responders with subsequent response to vedolizumab (n=8): median 9.5 pg/mL versus 5.9 pg/mL, p<0.05. Following stratification by diagnosis, patients with Crohn’s disease who failed vedolizumab therapy (n=7) had higher soluble CD40 ligand (sCD40L) than responders (n=4): 153.0 pg/mL versus 45.5 pg/mL, p<0.01; sensitivity 100% (95% CI 59% to 100%), specificity 100% (95% CI 40% to 100%). Osteocalcin was higher among patients with ulcerative colitis responding to vedolizumab (n=4) compared with those not responding (n=13): 4219 pg/mL versus 2823 pg/mL, p=0.01; sensitivity 85% (95% CI 55% to 98%), specificity 100% (95% CI 40% to 100%).ConclusionsPatients with IBD failing vedolizumab induction and anti-TNF therapy have persistent IL-6 pathway activity, which could be a potential alternative treatment target. sCD40L, osteocalcin and the IL-6 pathway activity might be predictors for response to vedolizumab.

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Section: Discussionmentioning

confidence: 75%

Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD

Soendergaard

Seidelin

Steenholdt

et al. 2018

BMJ Open Gastroenterol

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“…PNR after the initiation of TNF-α inhibitors need to be assessed early due to their poor prognosis [7]. However, the response rate can gradually increase from the first to the third administration of TNF-α inhibitors [4, 9].…”

Section: Summary Of the Meetingmentioning

confidence: 99%

“…Thus, in clinical settings, there are partial responders (PR) categorized as neither PNR nor responders, who display a partial response without satisfying effects in the induction phase of TNF-α inhibitors. Primary treatment failure of TNF-α inhibitors can be associated with poor long-term outcomes, including a high risk of surgery or sustained active disease despite medical interventions [7]. Patients who failed to obtain an ideal initial response show poor outcome, while Buhl et al [8] reported that the population with deep remission increased to 25% at 2 years after IFX initiation among patients who had partial response after 1 year of IFX treatment.…”

Section: Introductionmentioning

confidence: 99%

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

et al. 2020

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Induction therapy with tumor necrosis factor-α (TNF-α) inhibitors is highly effective for the treatment of Crohn’s disease. However, there are primary nonresponders (PNR) of TNF-α inhibitors without clinical response during the induction period. In addition, there are partial responders (PR), who show some efficacy, but clinical remission is not achieved by induction therapy. To date, the definition and clinical management of PNR and PR have not been established. This report summarizes the opinions of 36 Japanese experts attending the Japan Round Table Discussion on IBD Meeting regarding how to determine PNR and PR of TNF-α inhibitors and how to manage these patients in clinical practice. PNR, who do not show any initial improvement of clinical symptoms and serum C-reactive protein (CRP) levels, require re-assessment of intestinal complications. PR can be determined either by clinical symptoms, serum CRP levels, or imaging results. PR need intensification of the treatment with TNF-α inhibitors either with or without optimization of immunomodulators. Optimization of initial TNF-α inhibitor therapy may improve long-term outcomes, but more evidence is required to improve the use of TNF-α inhibitors for the prevention and management of PNR and PR.

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“…Importantly, patients with primary failure of IFX often had no response to the second-line biologic drugs, thus leading to prolonged disease activity (Roblin et al, 2018;Roblin et al, 2020). So far, there is no international consensus on how to handle IBD patients with failure of anti-TNF (Allez et al, 2010;Papamichael et al, 2015;Buhl et al, 2017). Appropriately choosing other therapies after anti-TNF failure was a common challenge to clinicians, yet little is known about the prognosis after the failure in the long term (Hanauer et al, 2002;Allez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn’s Disease

Ding

Liu

et al. 2021

Front. Pharmacol.

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Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn’s disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation.Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The “one-hour FMT protocol” was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis.Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43–6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001–0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002).Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD.Clinical Trial Registration:https://clinicaltrials.gov, identifier NCT01793831

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Outcomes After Primary Infliximab Treatment Failure in Inflammatory Bowel Disease

Abstract: Primary infliximab treatment failure is associated with poor outcome including high risk of surgery or sustained active disease despite medical interventions.

Cited by 21 publications

References 40 publications

Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD

Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD

Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn’s Disease

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