Corrigendum to: Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients with Crohn Disease: Posthoc Analysis of the LOVE-CD Study

Abstract Background Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD. Methods Data were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD < 4). Results Linear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively. Conclusions Model-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.

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Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa301 ◽

2020 ◽

Author(s):

Hyuk Yoon ◽

Sushrut Jangi ◽

Parambir S Dulai ◽

Brigid S Boland ◽

Vipul Jairath ◽

...

Keyword(s):

Treatment Failure ◽

Crohn Disease ◽

Lower Risk ◽

Hazard Analysis ◽

Cumulative Risk ◽

Treatment Optimization ◽

Cox Proportional Hazard ◽

Endoscopic Remission ◽

Risk Of Treatment

Abstract Background Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status. Methods In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis. Results Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity. Conclusions Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.

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Predictors of Long-term Clinical and Endoscopic Remission in Children With Crohn Disease Treated With Infliximab

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0000000000002262 ◽

2019 ◽

Vol 68 (6) ◽

pp. 841-846 ◽

Cited By ~ 3

Author(s):

Giulia D’Arcangelo ◽

Salvatore Oliva ◽

Anna Dilillo ◽

Franca Viola ◽

Fortunata Civitelli ◽

...

Keyword(s):

Crohn Disease ◽

Endoscopic Remission

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Imatinib in Refractory Crohn Disease: A Series of 6 Cases

Crohn's & Colitis 360 ◽

10.1093/crocol/otz034 ◽

2019 ◽

Vol 1 (3) ◽

Author(s):

Anna Boctor ◽

Jean-Pierre Hugot ◽

Thierry Leblanc ◽

Christine Martinez-Vinson ◽

Matthieu Allez ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase Inhibitor ◽

Crohn Disease ◽

Myeloid Leukemia ◽

Digestive Disease ◽

Kinase Inhibitor ◽

Positive Impact ◽

Therapeutic Options ◽

Loss Of Response ◽

Endoscopic Remission

Abstract Biologics have revolutionized Crohn disease (CD) treatment. Nevertheless, absence or loss of response is frequent and alternative therapeutic options may be necessary. Imatinib is a tyrosine kinase inhibitor that is used in chronic myeloid leukemia. A positive impact on CD in 2 patients with chronic myeloid leukemia treated with imatinib led us to propose the drug in 4 additional patients with refractory CD. Four out of these 6 patients reached clinical and endoscopic remission at a median time of 3 months. Remission was maintained for 9 months to 7 years. Imatinib may thus be considered as new therapeutic options for refractory CD. We report 6 CD patients treated with imatinib. Two of them because of a leukemia and 4 because of a disease refractory to all medical options. Four patients experienced full and sometimes prolonged remission of their digestive disease.

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