Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn’s Perianal Fistulas

Gregorio, Michael De; Lee, Tanya; Krishnaprasad, Krupa; Amos, Gregory; An, Yoon‐Kyo; Bastian-Jordan, Matthew; Borok, Nira; Brown, Dougal; Cheung, Wa; Connor, Susan J.; Gerstenmaier, Jan; Gilbert, L; Gilmore, Robert; Kutaiba, Numan; Lee, Allan; Mahy, Gillian; Srinivasan, Ashish; Thin, Lena; Thompson, Alexander; Welman, C.; Yong, Eric; Cruz, Peter P De; Langenberg, Daniel R. van; Sparrow, Miles P.; Ding, Nik S.

doi:10.1016/j.cgh.2021.07.053

Cited by 20 publications

(8 citation statements)

References 19 publications

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“…In doing so, it is important to acknowledge the relationship between objective endpoints such as biomarker normalization, radiologic healing, and endoscopic remission and higher infliximab levels, compared with clinical endpoints alone. [16][17][18][19] Here, we showed that higher infliximab levels both at week 6 (18.45 vs 5.36 ug/mL, P < 0.01) and 12 (8.94 vs 5.96 ug/mL, P = 0.02) were achieved following re-induction. Also, a higher proportion of patients achieved immediate treat-to-target success at week 12 following re-induction (49%) than 6-weekly (37%) dose interval shortening, although these findings were not statistically significant (P = 0.38).…”

Section: Discussionmentioning

confidence: 51%

Dose intensification strategy influences infliximab pharmacokinetics but not clinical response after the same number of doses

Srinivasan

Cruz

Sam

et al. 2023

J of Gastro and Hepatol

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Background The optimal infliximab dose intensification strategy to address secondary loss of response (LOR) remains unclear. This study aimed to compare clinical and pharmacokinetic outcomes following (i) upfront infliximab re‐induction with (ii) ongoing 6‐weekly dose interval shortening (DIS), after the same number of doses. Methods A prospective parallel cohort study of inflammatory bowel disease patients who required infliximab dose intensification for secondary LOR using (i) re‐induction (i.e., repeat 5 mg/kg 0, 2, 6‐week dosing) followed by 8‐weekly maintenance or (ii) 6‐weekly 5 mg/kg DIS was undertaken. Week 32 clinical response was the primary outcome, with secondary evaluation of infliximab pharmacokinetics and predictors of response. Results Of 104 patients, 54 underwent re‐induction, and 50 underwent 6‐weekly DIS; 43 per cohort had clinically active disease, with comparable baseline infliximab levels (2.03 vs 2.02 ug/mL, P = 0.83). Clinical response was similar across re‐induction and DIS cohorts at weeks 12 (69.8 vs 65.1%) and 32 (53.5 vs 62.8%, each P > 0.50); however, both strategies demonstrated distinct pharmacokinetic profiles at weeks 6 (18.45 vs 5.36 ug/mL, P < 0.01), 12 (8.94 vs 5.96 ug/mL, P = 0.02) and 30 (3.89 vs 6.35 ug/mL, P = .0.02). In multivariable analyses, objectively verified active disease at baseline (OR 12.92, 95% CI [1.84–90.84], P = 0.01), subtherapeutic week 6 infliximab levels (OR 0.12, 95% CI [0.01, 0.99], P = 0.049) and week 12 clinical response (OR 5.44, 95% CI [1.20–19.97], P = 0.04) were associated with week 32 response, as were week 2 infliximab levels (OR 1.34, 95% CI [1.02–1.47], P = 0.04) following re‐induction. Following re‐induction, week 2 infliximab levels <15.6 ug/mL (AUROC 0.76, 95% CI [0.54–0.99], P < 0.05) predicted nonresponse at week 32. Conclusion Dose intensification strategy impacted immediate and sustained infliximab levels but not clinical response. Upfront intensification was associated with short‐term pharmacokinetic advantages, including predictors of response, that diminished with time. Hence, when applying upfront dose intensification, clinicians should consider continuing intensified dosing to sustain early pharmacokinetic advantages based on predictors of (non)response.

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Section: Discussionmentioning

confidence: 51%

Dose intensification strategy influences infliximab pharmacokinetics but not clinical response after the same number of doses

Srinivasan

Cruz

Sam

et al. 2023

J of Gastro and Hepatol

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“…However, there is evidence that prolonged IFX therapy in patients with pfCD may increase the benefit [29]. Additional evidence suggests that dose monitoring and higher serum concentrations are associated with better clinical outcomes [27,30,31]. Similarly, drug concentration monitoring and dosing optimization could be expected to be equally beneficial for the outcome of patients with lfCD, but in our study, concentration monitoring did not improve nonsurgical survival, possibly due to the tendency of multidisciplinary teams to promote surgical procedures in clinical decision-making for patients with suboptimal drug concentrations, leading to inconsistent conclusions.…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn’s disease

Zhang

Liu

et al. 2023

BMC Gastroenterol

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Background Enteric fistula is one of the penetrating features in Crohn’s disease (CD). This study aimed to clarify the prognostic factors for the efficacy of infliximab (IFX) treatment in luminal fistulizing CD patients. Methods We retrospectively included 26 cases diagnosed with luminal fistulizing CD hospitalized in our medical center from 2013 to 2021. The primary outcome of our research was defined as death from all causes and undergoing of any relevant abdominal surgery. Kaplan–Meier survival curves were used to describe overall survival. Univariate and multivariate analyses were used to identify prognostic factors. A predictive model was constructed using Cox proportional hazard model. Results The median follow-up time was 17.5 months (range 6–124 months). The 1- and 2-year surgery-free survival rates were 68.1% and 63.2%, respectively. In the univariate analysis, the efficacy of IFX treatment at 6 months after initiation (P < 0.001, HR 0.23, 95% CI 0.01–0.72) and the existence of complex fistula (P = 0.047, HR 4.11, 95% CI 1.01–16.71) was found significantly related to the overall surgery-free survival, while disease activity at baseline (P = 0.099) also showed predictive potential. The multivariate analysis showed that efficacy at 6 months (P = 0.010) was an independent prognostic factor. The C-index of the model for surgery-free survival was 0.923 (P < 0.001), indicating an acceptable predictive effect. Conclusion Prognostic model including the existence of complex fistula, disease activity at baseline and efficacy of IFX at 6 months may be useful to predict long-term outcome of luminal fistulizing CD patients.

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“…Interestingly, a recent analysis using magnetic resonance images from patients with CD identified surprisingly low IFX thresholds of 4.0 mg/mL and 6.5 mg/mL for radiologic healing and remission, respectively. 56 These data remind us that there is no universal cutoff for biologic serum concentrations and that they almost certainly vary between individuals and also between studies due to other factors such as interassay variability.…”

Section: Perianal Crohn's Diseasementioning

confidence: 96%

Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

Irving

Gecse

2022

Gastroenterology

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Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn’s Perianal Fistulas

Cited by 20 publications

References 19 publications

Dose intensification strategy influences infliximab pharmacokinetics but not clinical response after the same number of doses

Dose intensification strategy influences infliximab pharmacokinetics but not clinical response after the same number of doses

Prognostic factors for the efficacy of infliximab in patients with luminal fistulizing Crohn’s disease

Optimizing Therapies Using Therapeutic Drug Monitoring: Current Strategies and Future Perspectives

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