6ER-013 Analysis of biological treatments as possible therapeutic alternatives in refractory anti-tnf patients in crohn’s disease

Background At the moment the main treatment goals in Crohn’s desease (CD) are to induce and maintain remission, controlling inflammatory activity to keep the patient free of symptoms and avoid complications. Purpose To establish whether vedolizumab and ustekinumab can be declared equivalent therapeutic alternatives (ETA) in patients pretreated with anti-TNF in CD through indirect comparisons (IC) using a common comparator. Material and methods A search was done to identify phase III clinical trial (CT) with biological treatments on CD, similar population, duration and same primary endpoint. CT included were: double-blind, randomised, placebo-controlled, patients with refractory CD, with induction and maintenance phase. Primary endpoint was the clinical response in the induction phase and clinical remission in the maintenance phase, defined by the Mayo score. An IC was done using the Bucher method (ITC calculator, IndirectTreatmentComparisons, from the CanadianAgency forHealth Technology Assessment). As a delta value (Δ), maximum acceptable difference as a clinical criterion of no-inferiority was settles in 15%. However, given the reduced efficacy of the reference drug, vedolizumab (16.9%), it seemed appropriate to rate 8.5% as a limit to ensure half the efficacy. Both drugs were compared because of its indication in patients refractory to anti-TNF. Positioning was established following the ETA Guide. Results Five CT (three induction and two maintenance) were reviewed but adjusted indirect comparison was only possible in the induction phase (vedolizumab=16.9%–95% CI: 6.8 to 26.9), (ustekinumab=12.35%, 95% CI: 4.5 to 20.1). Using the Bucher method, a response difference of −4.6% was calculated (95% CI: −17 to 8, p>0,05). The IC exceeds the equivalence margin. With the method of Shakespeare et al., the probability of a difference in response between both drugs was found to be less than 8.5% or 15%, respectively, by 73% or 95%. Conclusion Both drugs have shown modest efficacy in the induction phase. We can state that there is a probable clinical equivalence between both drugs, as there is uncertainty about whether there is a real difference, as it is not statistically significant. In order to classify it as ETA, the potential consequences for the patient are assessed and as failure does not cause serious/irreversible harm to the patient, meeting both criteria for clinical response in the induction phase. References and/or Acknowledgements 1. European Public Asessment Report. (Accessed: 13 October 2016). Disponible:http://www.ema.europa.eu/docs/es_ES/document_library/EPAR__Product_Information/human/002782/WC500168528.pdf No conflict of interest