{ "abstract": "Introduction Combining thiopurines (TP) with intravenous (IV) infliximab (IFX) decreases the rate of immunogenicity. Subanalyses of registration studies show that subcutaneous (SC) IFX may be associated with a decreased chance of developing anti-drug antibodies (ADAb). However, there are no randomised controlled trials (RCT) to inform the decision of whether to continue or discontinue TP when switching from IV to SC IFX.Methods We conducted a multicentre, RCT of TP withdrawal in patients switching from IV to SC IFX. Patients with IBD in stable remission (HBI ≤4 or SCCAI ≤2 ) who had been receiving IV IFX for at least 22 weeks at stable doses of up to 5mg/kg q4w or 10mg/kg q8w along with a TP were randomised to continue or discontinue the TP. Patients had therapeutic IFX drug levels (DL) at screening and were stratified by HLA DQA1*05 status. Primary outcome was the proportion of patients who developed free antidrug antibodies (ADAb) at week 24 (ie detectable antibodies in the absence of detectable drug). Using a non-inferiority design to detect a 15% difference, 102 patients were required to meet the target of 88 evaluable patients at week 24.Results 102 patients (63=CD, 39=UC, 5=IBD-U) were randomised. For the primary outcome, detection of free ADAb at 24W, 88 patients were evaluable (2 patients withdrew early, 8 patients attended outside 1 week window for week 24 assessment, 4 patients did not provide week 24 samples). TP withdrawal was non inferior to continuation (difference -2.4 (95% CI: -12.3 to 5.4) P=0.46). 1/41 patients in the stop group developed free ADAb compared with 0/47 in the continue group; a sensitivity analysis including the samples from the early withdrawal patients and the patients who provided late samples at week 24, none of whom developed free ADAb, did not change the outcome. HLA DQA1*05 status did not affect IFX DL, nor free or total ADAb formation. Median IFX levels (ug/ml) at weeks 8, 16 and 24 were 15.5, 17.7 and 18.4 in the continue arm vs 17.0, 15.5 and 15.1 in the stop arm. The proportion of patients with total positive ADAb at the same time points was 21%, 22% and 20% (continue) and 12%, 15% and 18% (stop). There was no difference at week 24 in clinical disease activity (HBI >4, SCCAI>2), biomarker activity (FC >250 ug/g or CRP >5 mg/L) or combined clinical and biomarker activity ( figure 1). One patient reverted to IV IFX (stop group), one patient required admission for pneumonia and one patient developed a basal cell carcinoma (both continue group).Conclusions IBD patients in stable remission on combination therapy with IV IFX and TP can be safely switched to SC IFX without the need for continuation of the thiopurine to prevent ADAb.Abstract O62 Figure 1(A) Primary outcome - non inferiority at week 24, (B) disease activity at week 24, (C) IFX levels at weeks 8,16 and 24 and (D) total antidrug antibodies at weeks 8, 16 and 24", "authors": [ { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom", "King’s College London, London, United Kingdom" ], "name": "Peter Irving" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom" ], "name": "Andrea Centritto" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom" ], "name": "Xin Yi Choon" }, { "affiliations": [ "University College London Hospitals NHS Foundation Trust, London, United Kingdom" ], "name": "Jie Han Yeo" }, { "affiliations": [ "University College London Hospitals NHS Foundation Trust, London, United Kingdom" ], "name": "William Blad" }, { "affiliations": [ "Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom" ], "name": "Alison Talbot" }, { "affiliations": [ "Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom" ], "name": "Abbie-Lei Fitzgerald" }, { "affiliations": [ "Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom" ], "name": "Emma Whitehead" }, { "affiliations": [ "Western General Hospital - NHS Lothian, Edinburgh, United Kingdom" ], "name": "Alex Elford" }, { "affiliations": [ "St George’s University Hospital NHS Foundation Trust, London, United Kingdom" ], "name": "Michael Colwill" }, { "affiliations": [ "St George’s University Hospital NHS Foundation Trust, London, United Kingdom" ], "name": "Samantha Baillie" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom" ], "name": "Rashida Pramanik" }, { "affiliations": [ "King’s College London, London, United Kingdom" ], "name": "Salma Ayis" }, { "affiliations": [ "King’s College London, London, United Kingdom" ], "name": "Aicha Goubar" }, { "affiliations": [ "Synnovis LLP, Purine Research Lab, London, United Kingdom" ], "name": "Monica Arenas-Hernandez" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom" ], "name": "Jessica Cordle" }, { "affiliations": [ "Western General Hospital - NHS Lothian, Edinburgh, United Kingdom", "University of Edinburgh, Edinburgh, United Kingdom" ], "name": "Charlie Lees" }, { "affiliations": [ "St George’s University Hospital NHS Foundation Trust, London, United Kingdom" ], "name": "Richard Pollok" }, { "affiliations": [ "Hull University Teaching Hospitals NHS Trust, Hull, United Kingdom" ], "name": "Shaji Sebastian" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom", "King’s College London, London, United Kingdom" ], "name": "Robin Dart" }, { "affiliations": [ "Guy’s And St Thomas’ Hospital, London, United Kingdom" ], "name": "Mark Samaan" }, { "affiliations": [ "University College London Hospitals NHS Foundation Trust, London, United Kingdom" ], "name": "Paul Harrow" } ], "title": "O62 Randomised controlled trial of withdrawal of thiopurines when switching from intravenous to subcutaneous infliximab: results of the MINIMISE study", "uid": "0fef889f-f8f8-5e96-915c-0056ddb7e8b7" }