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OC-001 Clinical Factors that Determine Primary Non-Response (PNR) to anti-TNF Drugs in Patients with Active Luminal Crohn’s Disease (CD)
  1. GA Heap1,2,
  2. T Ahmad1,2,
  3. on behalf of Pants Consortium
  1. 1Department of Gastroenterology, Royal Devon & Exeter Hospital
  2. 2Precision Medicine Exeter, University of Exeter, Exeter, UK


Introduction 10–40% of patients with CD fail to respond to anti-TNF induction therapy at 10–14 weeks. The mechanisms underlying PNR are uncertain but a better understanding of these factors might allow more cost-effective, individualised anti-TNF treatment. We present an interim analysis of PNR in the PANTS cohort.

Methods The PANTS study is a UK wide, multi-centre 3 year prospective, observational cohort study investigating PNR to Infliximab (IFX) and Adalimumab (ADA). Serial collection of clinical data and sampling of DNA, RNA, serum and stool will allow down-stream multi-omic studies. Inclusion criteria include active luminal Crohn’s disease supported by raised CRP or Calprotectin and no prior exposure to anti-TNF therapy. PNR was defined as failure of HBI to fall by ≥3 points or to ≤4 AND failure of CRP to fall by ≥50% or to ≤3  mg/dL OR failed steroid withdrawal. Drug and anti-drug antibody levels were measured using Immunodiagnostic drug tolerant assays.

Results 1176 (568 male) patients aged 4.0–77.2 years have been recruited from 106 sites and reached 14 weeks after quality control. Patients were treated with IFX (695, 59.1%) or ADA (481, 40.9%). At entry 39.7% of patients had an HBI of ≤4, 32.14% ≥ 8, and 29.4% of patients had a CRP ≤ 3, 42.4% had a CRP ≥ 10. Concomitant drugs at entry included steroids 18.5%, azathioprine 39.2%, mercaptopurine 7.40%, methotrexate 5.4%. PNR could be assessed at week 14 for 1090 (92.7%) patients. PNR was observed in 16.9% and 23.7% of the IFX and ADA treated patients respectively. This difference was not significant once adjusted for baseline disease activity (P = 0.2). To date only 2 patients who met the week 14 PNR criteria achieved remission on anti-TNF at 1 year (sensitivity 0.99, specificity 0.4). A multivariate regression identified albumin (P = 0.0036) as associated with PNR at Week 14 in the IFX group and drug level (P = 0.00035), calprotectin (P = 0.033), albumin (P = 0.037) and anti-drug antibody level (P = 0.024) in the ADA group. In combined analysis BMI (P = 0.017) and drug level (P = 0.024) were associated with PNR. 75 IFX and 36 ADA patients had anti-drug antibodies at week 14, of which 33 and 6 patients had no detectable drug. Development of anti-drug antibodies in the first 14 weeks was associated with monotherapy (P = 0.00021) and was seen more commonly in patients with early infusion reactions (P = 2x10−16).

Conclusion The PANTS study has provided a real world estimate of PNR and associated risk factors in a large prospective cohort using a simple clinical and biochemical definition at week 14 that predicts non-remission at week 54. Low drug level and immunogenicity are associated with PNR, infusion reactions and monotherapy suggesting early measurement might help prevent and manage PNR.

Disclosure of Interest G. Heap Conflict with: Abbvie, T. Ahmad Grant/research support from: Abbvie, MSD, Hospira, Inflectra, Conflict with: Abbvie, MSD

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