Efficacy of Vedolizumab as Induction Therapy in Refractory IBD Patients

Abstract

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials.

Crohn’s Disease Biologic Therapies Advances: A current review

“…An adverse event was seen in 10.5% of patients, five of whom were worsening arthropathy and one a new pyoderma gangrenosum (see [22]. VDZ led to a clinical improvement in the majority of IBD patients and was well tolerated, however, the adverse events were higher than expected [15,22].…”

“…The integrins α4β1, α4β7, αEβ7 and αLβ2 are the main receivers who contribute to this infiltration [12]. The α4β7 integrin, expressed in auxiliary and memory T cells, bind in mucosal vascular addressin cell adhesion molecular 1 (MAdCAM-1) expressed on the endothelial cells, playing an important role in the coupling of the T cells to the membrane [15]. Anti-integrin therapy modulates the inflammation by binding some of these integrins, which has an overall effect of preventing inflammation in the gut through inhibition of leukocyte migration into the mucosa.…”

“…Those who do not respond to the first anti-TNF-α have lower response rates to the second or third with this kind of therapy. Several studies demonstrated that anti-TNF therapy is associated with side effects that include serious infections and malignancies [15]. New drug options with alternative actions were created, including Natalizumab, Vedolizumab (VDZ), Ustekinumab, Secukinumab, among others [11].…”

Recent trends and future directions for the medical treatment of ulcerative colitis

“…Thus, vedolizumab may be useful for patients who are not responsive to anti-TNF treatment. Other cohort studies also indicated a relatively high clinical response (50-53 % at week 14) [52,53] or marked decreases in the partial Mayo score at week 6 [54], which was observed although the patients had not been randomized. The adverse effects were comparable between the vedolizumab group and placebo group in most studies.…”

Immunephenotype Predicts Response to Vedolizumab: Integrating Clinical and Biochemical Biomarkers in the Treatment of Inflammatory Bowel Diseases

“…Nevertheless, similar to anti-TNFα agents, a significant proportion of patients (≈ 40%) failed to reach or to maintain remission in response to vedolizumab. In real-word cohorts, the primary response rate to vedolizumab is effectively similar in UC and CD patients, 40-60% of patients [5,6]. Lack of response or need for dose optimization occurs in 40-60% of IBD patients during the maintenance phase [7,8].…”