ABSTRACT
BACKGROUND & AIMS: Vedolizumab is used to treat patients with ulcerative colitis (UC), although there is a delay before it is effective. Induction therapy with a calcineurin inhibitor (cyclosporine or tacrolimus) in combination with vedolizumab as maintenance therapy could be an option for patients with an active steroid-refractory UC. We assessed the efficacy and safety of this combination. METHODS: We performed a retrospective observational study, collecting data from 12 referral centers in France that were included in the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif. We collected information on 39 patients with an active steroid-refractory UC (31 with active severe UC and 36 failed by treatment with a tumor necrosis factor antagonist) who received a calcineurin inhibitor as induction therapy along with vedolizumab as maintenance therapy. Inclusion date was the first vedolizumab infusion. The outcomes were survival without colectomy, survival without vedolizumab discontinuation, and safety. RESULTS: After a median follow-up period of 11 months, 11 patients (28%) underwent colectomy. At 12 months, 68% of the patients survived without colectomy (95% CI, 53%-84%) and 44% survived without vedolizumab discontinuation (95% CI, 27%-61%). No deaths occurred and 4 severe adverse events were observed. CONCLUSIONS: In a retrospective analysis of 39 patients with an active steroid-refractory UC (most refractory to a tumor necrosis factor antagonist), we found that initial treatment with a calcineurin inhibitor in combination with vedolizumab allowed more than two thirds of patients to avoid colectomy. Further studies are needed to assess the safety of this strategy.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Calcineurin Inhibitors/administration & dosage , Colitis, Ulcerative/drug therapy , Drug Therapy, Combination/methods , Gastrointestinal Agents/administration & dosage , Induction Chemotherapy/methods , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Calcineurin Inhibitors/adverse effects , Drug Therapy, Combination/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , France , Gastrointestinal Agents/adverse effects , Humans , Induction Chemotherapy/adverse effects , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer in the world and the third leading cause of death. Unfortunately, when diagnosed two thirds of patients have an advanced disease for which only palliative treatment can be proposed and most likely systemic therapy. Areas covered: As of today only one systemic therapy is validated in the treatment of advanced HCC, a tyrosine kinase inhibitor (TKI): Sorafenib. Treatment options are therefore lacking. With the advent of Sorafenib other TKIs have been studied with some disappointing results. Many explanations can be found to the failure of these tested TKIs such as the underlying cirrhosis leading to rapidly serious adverse events, or trial design imperfections. Expert opinion: Taking into account these failures, new trials with more appropriate designs have led to recent success with multi-target TKIs (Regorafenib and Lenvatinib). This multi-target approach allows to overcome the molecular heterogeneity of advanced HCC which is associated with multiple simultaneously dysregulated signaling pathways. On the contrary, another lead is to study target a specific TKI such as c-MET inhibitors or TGFßR inhibitors in HCC sub-populations with promising results in early phase trials. These results will have to be validated in the ongoing phase III trials.
