Correction to: Vedolizumab Concentrations Are Associated with Long-Term Endoscopic Remission in Patients with Inflammatory Bowel Diseases.

The original version of the article unfortunately contained a couple of errors. In 'methods' section, in 'Outcomes' subsection, the sentence 'Endoscopic remission was defined as an SESCD ≤ 2 in patients with CD and an EMS ≤ 2 in UC patients while off corticosteroids.'

Vedolizumab Concentrations Are Associated with Long-Term Endoscopic Remission in Patients with Inflammatory Bowel Diseases.

BACKGROUND: The aim of this study was to assess the relationship of serum vedolizumab concentrations (SVC) during induction and endoscopic remission in patients with inflammatory bowel diseases (IBD) after 52 weeks of therapy with vedolizumab. We also sought to assess the incidence of antibody to vedolizumab (ATV) formation, the effect of ATV on drug pharmacokinetics and efficacy, and identify variables associated with SVC through the first 30 weeks of treatment. METHODS: This is a prospective cohort study of patients with active IBD initiating standard therapy with vedolizumab. Collected variables included demographics, clinical disease activity, biomarkers, pre-infusion SVC, and ATV measured at weeks 2, 6, 14, 22, and 30. Primary outcome was steroid-free endoscopic remission at week 52. RESULTS: Fifty-five patients were included. Patients that achieved steroid-free endoscopic remission by week 52 had higher SVC at weeks 2, 6, 14, 22, and 30, but only achieved statistical significance at weeks 2 and 6. Only 3 out of the 55 study subjects (5.5%) had detectable ATV through the follow-up. Overall, there were a positive correlation between SVC and serum albumin and a negative correlation with C-reactive protein, fecal calprotectin, and body mass. Vedolizumab concentrations ≥ 23.2 mcg/ml at week 2 were associated with endoscopic remission at week 52 (OR 8.8 [95% CI 2.6-29.7], p < 0.001). CONCLUSIONS: Vedolizumab concentrations during induction were associated with endoscopic remission at week 52. Interventional studies looking into improved efficacy with higher drug exposure are warranted.

Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity.

BACKGROUND: Chronic rejection is a major cause of graft loss in kidney transplant recipients. Nonadherence to drug therapy is a well-recognized cause of chronic rejection leading to long-term graft dysfunction and failure for transplant recipients. Immunosuppressive medications with short half-lives that require frequent dosing, such as tacrolimus, complicate transplant regimens and may increase noncompliance. Regimens could be simplified using drugs with long half-lives requiring once-daily administration, such as sirolimus. The impact of missing doses of single agents has not been studied extensively. Erratic compliance or temporary discontinuation of immunosuppressive drugs may have significant implications for chronic rejection. METHODS: Our study evaluated the impact of single drug withdrawal of commonly used immunosuppressive agents (sirolimus and tacrolimus) on lymphocyte responses. We analyzed lymphocyte proliferation, cytokine secretion, and adenosine triphosphate generation using a crossover study design with normal healthy patients. Lymphocyte proliferation was assessed using 5-bromo-2-deoxyuridine incorporation, and T cell function was analyzed by examining adenosine triphosphate generation. RESULTS: Our results indicate that sirolimus exerts prolonged suppression of lymphocyte proliferation and decreased interleukin 17A that lasts up to 48 h after drug withdrawal. In comparison, tacrolimus did not have a similar effect on lymphocyte proliferation or interleukin 17A secretion. CONCLUSION: Future analysis of sirolimus in diverse transplantation populations merits investigation.

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Vedolizumab is an anti-α4ß7 biologic approved for ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission. METHODS: We performed a cross-sectional multi-centre study of inflammatory bowel disease [IBD] patients on maintenance vedolizumab. A homogeneous mobility shift assay [HMSA] was used to determine trough serum concentrations of vedolizumab and anti-drug antibodies [ATVs]. The primary outcome was corticosteroid-free clinical and biochemical remission defined as a composite of clinical remission, normalized C-reactive protein [CRP] and no corticosteroid use in 4 weeks. Secondary outcomes included corticosteroid-free endoscopic and deep remission. Vedolizumab concentrations were compared between patients in remission and with active disease. Logistic regression, adjusting for confounders, assessed the association between concentrations and remission. RESULTS: In total, 258 IBD patients were included [55% CD and 45% UC]. Patients in clinical and biochemical remission had significantly higher vedolizumab concentrations [12.7 µg/mL vs 10.1 µg/mL, p = 0.002]. Concentrations were also higher among patients in endoscopic and deep remission [14.2 µg/mL vs 8.5 µg/mL, p = 0.003 and 14.8 µg/mL vs 10.1 µg/mL, p = 0.01, respectively]. After controlling for potential confounders, IBD patients with vedolizumab concentrations >11.5 µg/mL were nearly 2.4 times more likely to be in corticosteroid-free clinical and biochemical remission. Only 1.6% of patients had ATVs. CONCLUSIONS: In a large real-world cohort of vedolizumab maintenance concentrations, IBD patients with remission defined by objective measures [CRP and endoscopy] had significantly higher trough vedolizumab concentrations and immunogenicity was uncommon.