Sa1269 Adjunctive Allopurinol in Azathioprine/6-Mercaptopurine Non-Responders Optimises 6-Thioguanine Nucleotide Production and Improves Clinical Outcomes in Inflammatory Bowel Disease: The Prospective, Multicentre, Double Blind, Dose-Ranging AAA Study

Abstract

Background: Infliximab (IFX) treatment failure in patients with Crohn's disease is generally handled by intensifying the IFX regimen. However, an alternative strategy defined by an algorithm based on serum IFX and anti-IFX antibody measurements to identify reasons for failure and corresponding interventions has been proposed. In a randomized controlled trial, we observed substantial cost reductions after 12 weeks when using this algorithm as compared to IFX intensification, and without negative influence on symptom control.(1) The current study primarily investigated long-term cost outcomes at time of the week 20 follow-up study visit and after 1 year. In addition, clinical outcomes were assessed at week 20. Methods: Predefined follow-up from a 12-week, single-blind, clinical trial where Crohn's disease patients with IFX treatment failure (CDAI ≥220 or ≥1 draining perianal fistula) were randomized to IFX intensification (5 mg/kg every 4 weeks) (n=36), or algorithm-defined interventions in form of IFX intensification, change to adalimumab, or use of pharmaceuticals other than TNF-inhibitors (n=33). Patients were treated at the discretion of the physician from week 12 onwards. Blinding was maintained until week 20. Accumulated costs, expressed as mean costs per patient, were based on the Danish National Patient Registry. Data were analyzed in the following populations: intention-to-treat (ITT) (n=69), per protocol (PP) (n=55), per protocol completion at end of trial week 12 (PPCw12) (n=45) or end of followup week 20 (PPCw20) (n=29). NCT00851565. Results: At the scheduled follow-up study visit at week 20, response (CDAI reduction ≥70 point or ≥50% reduction of active fistulas) and remission rates (CDAI ≤150 or closure of all fistulas) were similar in all study populations between patients treated by the algorithm or by IFX intensification (p>0.05). However, the sum of health care costs related to Crohn's disease was substantially lower (31%) for patients randomized to algorithm-based interventions than IFX intensification in the ITT population: $10,815 vs. $15,613; p<0.01. In the PP and PPw12 populations, costs at week 20 were even lower (49% and 50%) in the algorithm group: $7,919 vs. $15,613; p<0.01; and $7,714 vs. $15,455; p<0.01. In the PPCw20 population, costs were reduced by 60% in algorithmtreated patients: $6,391 vs. $16,101; p<0.001. The observed relative cost reductions (i.e. percentages) remained stable from week 20 until reassessment after one year, and were similar also when evaluating total health care costs irrespective of relation to Crohn's disease. Conclusion: Economic benefit of algorithm-based interventions at IFX failure is maintained throughout one year. (1) Steenholdt et al. Gut (2014)