Therapeutic drug monitoring of vedolizumab therapy in inflammatory bowel disease.

BACKGROUND: Therapeutic drug monitoring is effective for optimizing anti-tumor necrosis factor therapies in inflammatory bowel disease, but for vedolizumab, a gut-selective leucocyte migration inhibitor, data are scarce. METHODS: Observational cohort study including 116 bio-experienced inflammatory bowel disease patients treated with vedolizumab for active luminal disease. Biobanked trough blood samples (n = 676) covering 96% of patients were analyzed using a drug-binding immunofluorometric assay. Steroid-free treatment outcomes were classified by clinical disease activity indices and objective findings, primarily endoscopy. RESULTS: Patients with clinical remission to vedolizumab induction therapy (37%) had significantly higher trough levels than those without at weeks 6 (mean 34.1 vs 28.0 µg/mL, P = 0.03) and 10 (34.8 vs 27.5 µg/mL, P = 0.01). Optimal thresholds for discrimination were 32.4 µg/mL (AUCROC 0.66, P = 0.04) and 23.5 (AUCROC 0.67, P = 0.01), respectively. This positive association persisted during maintenance phase with 11.9 µg/mL (AUCROC 0.69, P < 0.01) associated with clinical remission (37%) and 15.3 (AUCROC 0.74, P < 0.001) for objective remission (46%). Stratification by temporal evolution of treatment effects revealed higher induction and maintenance vedolizumab levels in persistent and slow responders as compared to secondary or persistent failures. Pharmacokinetics was influenced by rare formation of anti-vedolizumab antibodies (2%), and to a lesser extent gender and albumin during induction, but not disease severity, concomitant steroids, or thiopurine metabolites. Switching to subcutaneous administrations resulted in 2.3-fold increase in steady-state trough levels. CONCLUSION: Our study supports maintaining adequate drug exposure being essential for sustained positive outcomes of vedolizumab and emphasizes individualized, therapeutic drug monitoring-based treatment regimens. Controlled trials and pharmacokinetic modeling are, however, needed.

Trajectories of health-related quality of life and fatigue during vedolizumab therapy in inflammatory bowel disease.

BACKGROUND AND AIM: Normalizing health-related quality of life (QoL) and fatigue are important long-term treatment targets in inflammatory bowel disease (IBD). We examined their evolution in relation to changes in disease activity during vedolizumab therapy. METHODS: Cohort study of biologically refractory IBD patients treated with vedolizumab. Patients were prospectively evaluated at all infusions by Short Health Scale (SHS) (QoL questionnaire covering four health dimensions) (n = 79), visual analogous scale for fatigue (VAS-F) (n = 30), and clinical disease activity. Objective disease assessment was carried out after 1 year or at treatment failure. RESULTS: Patients in steroid-free clinical remission at end of induction improved significantly in all SHS items already from week 2 with full implementation by week 14 ("Symptoms" 59% improvement, P < 0.001; "Function" 63%, P < 0.001; "Worries" 59%, P < 0.001; "Well-being" 40%, P < 0.01). Then, SHS remained stable at background levels (< 20) for 1 year (improvements 67%; 65%; 62%; 57%; P < 0.001). Combined clinical-objective remission at 1 year was associated with highest SHS improvements (64-72%; P < 0.001). Of note, early SHS improvements preceded manifestation of clinical remission in most patients (22 of 33; 67%). Clinical response materialized into late (week 6 or later) and minor SHS improvements (31-46%, P < 0.001). Fatigue improved steadily over 6 months to background levels (VAS-F < 4) among patients in clinical remission (45% decrease) or clinical-objective remission (41%). SHS and VAS-F impairment remained elevated in patients without effect of therapy. CONCLUSION: QoL rapidly improves and predicts later significant clinical-objective efficacies of vedolizumab at end of induction and 1 year. Fatigue improves slowly after remission is attained.