Higher Postinduction Infliximab Concentrations Are Associated With Improved Clinical Outcomes in Fistulizing Crohn's Disease: An ACCENT-II Post Hoc Analysis

Papamichael, Konstantinos; Casteele, Niels Vande; Jeyarajah, Jenny; Jairath, Vipul; Osterman, Mark T.; Cheifetz, Adam S.

doi:10.14309/ajg.0000000000001111

Cited by 46 publications

(34 citation statements)

References 36 publications

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“…A post hoc analysis of ACCENT-II RCT (282 patients after induction therapy and 139 patients on maintenance therapy) recently published by Papamichael et al [ 48 ] demonstrated that higher concentrations of IFX at week 14 were independently associated with composite remission defined as complete fistula closure and CRP normalization at week 14 (OR: 2.32; 95% CI: 1.55–3.49; p < 0.001) and week 54 (OR: 2.05; 95% CI: 1.10–3.82; p = 0.023). IFX concentrations predictive of composite remission were ≥20.2 μg/mL, ≥15 μg/mL and ≥7.2 μg/mL at weeks 2, 6, and 14, respectively.…”

Section: Tdm and Perianal Fistulizing CDmentioning

confidence: 99%

Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient

Nones

Fleshner

Queiroz

et al. 2021

JCM

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Despite significant development in the pharmacological treatment of inflammatory bowel diseases (IBD) along with the evolution of therapeutic targets and treatment strategies, a significant subset of patients still requires surgery during the course of the disease. As IBD patients are frequently exposed to biologics at the time of abdominal and perianal surgery, it is crucial to identify any potential impact of biological agents in the perioperative period. Even though detectable serum concentrations of biologics do not seem to increase postoperative complications after abdominal procedures in IBD, there is increasing evidence on the role of therapeutic drug monitoring (TDM) in the perioperative setting. This review aims to provide a comprehensive summary of published studies reporting the association of drug concentrations and postoperative outcomes, postoperative recurrence (POR) after an ileocolonic resection for Crohn’s disease (CD), colectomy rates in ulcerative colitis (UC), and perianal fistulizing CD outcomes in patients treated with biologics. Current data suggest that serum concentrations of biologics are not associated with an increased risk in postoperative complications following abdominal procedures in IBD. Moreover, higher concentrations of anti-TNF agents are associated with a reduction in colectomy rates in UC. Finally, higher serum drug concentrations are associated with reduced rates of POR after ileocolonic resections and increased rates of perianal fistula healing in CD. TDM is being increasingly used to guide clinical decision making with favorable outcomes in many clinical scenarios. However, given the lack of high quality data deriving mostly from retrospective studies, the evidence supporting the systematic application of TDM in the perioperative setting is still inconclusive.

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Section: Tdm and Perianal Fistulizing CDmentioning

confidence: 99%

Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient

Nones

Fleshner

Queiroz

et al. 2021

JCM

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“…In iximab was the rst proved effective biologics in promoting and maintaining CD-related stula closure, supported by high-quality randomized controlled trials (RCTs) with the primary endpoint as stula closure 5,10 . According to a multicenter, double-blind RCT conducted by Daniel and his colleagues 5 , 40% of patients had complete stula response at week 54 after scheduled in iximab administration.…”

Section: Discussionmentioning

confidence: 99%

“…Adalimumab is effective in treating stulizing CD with lower grade evidence though 11 . A majority of studies, prospective or retrospective, reported 30-50% of patients achieved clinical stula remission after long-term anti-TNF therapies 5,10,12 . Our results showed that a relatively lower percentage (23%) of patients presented stula closure.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Ustekinumab on perianal fistulizing Crohn’s disease: a retrospective single-center real-world analysis

Mao

Yao

Zhang

et al. 2022

Preprint

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Aim: Data of Ustekinumab (UST) in treating perianal fistulizing Crohn’s disease (CD) are limited in China. We aimed to evaluate the efficacy of UST in the real-world setting. Methods: We retrospectively analyzed patients with perianal fistulizing CD and receiving UST treatment from March 1, 2020 to October 30, 2021. Patients’ characteristics, biomarker, and imaging were extracted from digital databases. Results: Twenty patients were eligible (18 males; mean age of 29.4±2.6 years; mean disease duration of 6.3±0.9 years; 45.0% diagnosed as complex fistula; mean baseline Van Assche score of 7.7±1.1). Perianal Crohn’s disease activity index (5.4±1.0 vs 8.7±1.0, P=0.027) and Crohn’s anal fistula quality of life (29.4±4.8 vs 38.9±4.2, P=0.011) reduced significantly. Clinical remission appeared in 60.0% and clinical response in 85.0%; clinical fistula remission in 30.0%, clinical fistula response in 35.0%, and no response in 35.0% of patients. Eight patients received post-treatment MRI. Healing, partial response, no change, and deterioration appeared in 37.5%, 25.0%, 12.5% and 25.0% of the patients, respectively. The cut-off UST trough concentration predicting clinical fistula remission was 2.6 μg/ml (an area under the curve of 0.821, sensitivity 66.7%, specificity 85.7%). Conclusions: UST is efficacious in promoting clinical and radiological fistula remission in patients with CD.

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“…Although the infliximab cut-off differed from one study to another, it appears that the target level should be higher for pCD than for luminal CD. A recent subgroup analysis of the ACCENT II trial showed that a higher infliximab concentration at week 14 was associated with a fistula response (odds ratio (OR) [95%CI]: 1.16 [1.02–1.32]; p = 0.019) and a composite remission outcome (defined as complete fistula response plus the normalization of C-reactive protein (CRP) levels; OR: 2.32 [1.55–3.49]; p < 0.001) at week 14 ( Papamichael et al., 2021 ). Higher infliximab concentrations at week 14 were also associated with the composite remission outcome at week 54 (OR: 2.05 [1.10–3.82]; p = 0.023).…”

Section: Confirm the Failure Of Anti-tnf Treatmentmentioning

confidence: 99%

Managing complex perianal disease after anti-TNF failure: Where to go next?

Yzet

Brazier

Sabbagh

et al. 2022

Current Research in Pharmacology and Drug Discovery

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Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.

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Higher Postinduction Infliximab Concentrations Are Associated With Improved Clinical Outcomes in Fistulizing Crohn's Disease: An ACCENT-II Post Hoc Analysis

Cited by 46 publications

References 36 publications

Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient

Therapeutic Drug Monitoring of Biologics in IBD: Essentials for the Surgical Patient

Efficacy of Ustekinumab on perianal fistulizing Crohn’s disease: a retrospective single-center real-world analysis

Managing complex perianal disease after anti-TNF failure: Where to go next?

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