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PTH-088 Prevalence of low drug levels and anti-drug antibodies in an unscreened population of patients with inflammatory bowel disease receiving infliximab
  1. R Downey,
  2. G Tun,
  3. K Swallow,
  4. G Wild,
  5. K Robinson,
  6. A Wright,
  7. L Marshall,
  8. M Hale,
  9. R Sargur,
  10. AJ Lobo

Abstract

Introduction Infliximab (IFX) is widely used for induction and maintenance of remission in inflammatory bowel disease (IBD). It has been suggested that monitoring drug levels and antibodies to infliximab (ATI) may allow treatment optimisation.

The aim of this study was to examine the initial results, and their potential significance, from a programme of therapeutic drug monitoring (TDM), in a large, single, referral centre.

Method Since May 2016, all IBD patients receiving intravenous IFX for maintenance treatment have undergone TDM. Serum IFX trough levels and ATI were measured by a drug tolerant enzyme-linked immunosorbent assays (Biohit, UK). IFX trough levels were considered as undetectable (<0.8 mg/L), low (0.8–2.9 mg/L), therapeutic: (3–7 mg/L) or supratherapeutic (>7 mg/L). ATI were considered positive if >10 mg/L. Clinical remission was defined as a Harvey Bradshaw Index or Simple Colitis Activity Index≤4.

Results Initial screening of 162 maintenance patients (110 Crohn’s disease, 49 ulcerative colitis, 3 IBD-U; median age 36 years (16-82)), is shown in Table 1. Median duration of treatment was 88 weeks (range 12–581). 123/162 (76%) had drug levels that were undetectable (n=48) or low (n=75). Of these, 54/123 (44%) were ATI positive. 118/162 (73%) patients were in clinical remission, of whom 88/118 (75%) had low/undetectable drug levels while 35/44 (80%) patients with active disease had low/undetectable drug levels. Overall, 65 (40%) patients were ATI positive at initial screening. Positive ATI were associated with a lower level of IFX (median 1.4 vs 2.2 mg/L; p=<0.01, OR 2.97 (p<0.01) for undetectable levels).

In those ATI positive, infusion reactions occurred in 3/180 (1.7%) infusions vs 0/342 in those ATI negative (OR of 11.49, p=0.03).

Figure 1 shows the relationship between ATI status and IFX trough levels at initial TDM screening.

Conclusion In an unscreened population, 17% of patients have undetectable drug levels and positive ATI, and therefore, may derive no benefit from continued treatment, although 61% of those were in clinical remission. The high overall prevalence of sub-therapeutic drug levels is important in planning strategies to optimise dosing in a clinic setting. Although ATI detected by this assay are associated with a low risk of infusion reactions, these were more common than when ATI were negative.

Disclosure of Interest None Declared

  • Infliximab

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