Vedolizumab is a gut selective monoclonal antibody specific to the a4B7 integrin and had been studied for the induction and maintenance of response and remission in adult patients with moderate to severely active Crohn's disease (CD) in the GEMIMI clinical trials. Vedolizumab was FDA approved in May 2014 for adult patients with CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator (IMM); or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. Many patients with severe and aggressive CD in our research practice have been declared unresponsive and/or intolerant to anti-TNF and IMM therapy, failed experimental clinical trials utilizing other mechanisms, and have undergone extensive surgical interventions throughout the course of their disease. There is limited data about the outcomes of patients who have been treated with both high dose (monthly) vedolizumab and IMM therapies in combination. Our goal was to present a case series of these aggressive patient types evaluated retrospectively after receiving a year of combination therapy. By utilizing anti-integrin therapy in combination with an IMM, we sought an alternative medical approach for aggressive CD patients with limited other options for treatment.Methods:
Four patients, 1 male, 3 females, with long-standing aggressive CD were evaluated retrospectively. All had failed multiple prior therapies ranging from conventional treatments, multiple anti-TNF trials, and other experimental biologic therapies (anti-IL 12/23) All patients had predictors of poor outcomes with extended disease duration, inflammatory fistulous disease, recurrent surgeries, and lower albumin levels. These at-risk patients received monthly infusions of vedolizumab (300 mg) in combination with high dose IMM and were followed closely.Results:
All 4 patients were evaluated after 1 year of combination therapy; one of 4 patients achieved clinical remission, one patient is a partial responder and remains on combination therapy, and 2 patients were discontinued from vedolizumab. Both of the non-responders had previously failed off-label use of ustekinumab and had undergone surgical resection within 1 year preceding treatment and had documentation of recurrent post-surgical disease. One of the 2 non-responders was placed back on combination therapy with infliximab, and one is currently undergoing surgical evaluation. None of the 4 patients reported a serious adverse event.Conclusions:
Combination therapy with monthly vedolizumab and IMM for severe, treatment resistant CD can potentially induce remission in patients with prior loss of response to the anti-TNF mechanism. The role of IMM is unclear, but likely contributes to suppression of immunogenicity. Vedolizumab drug and antibody assays were not commercially available during the course of this study, but utilization of these levels levels may be helpful in guiding future therapy and in understanding potentiating effects IMM may have on vedolizumab. Blinded, placebo controlled trials are warranted to better understand combination therapy and its use in aggressive, treatment exposed CD patients.