P706 Adalimumab drug levels at secondary loss of response in Crohn’s disease; are we aiming high enough? A retrospective, international multi-centre study

A. Swaine1, R. Reynolds2, X. Roblin3, D. Gibson1, C. Martin4, P. Irving2, M. Sparrow1, M. Ward1

1Gastroenterology, Alfred Hospital, Melbourne, Australia, 2Gastroenterology, Guys and St Thomas’ Trust, London, UK, 3Gastroenterology, CHU de St. Etienne, St. Etienne, France, 4Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia

Background

Evidence supporting therapeutic drug monitoring with adalimumab (ADA) in Crohn’s disease (CD) is not as strong as for infliximab. Data examining whether changes in ADA drug exposure after dose intensification are associated with outcomes are lacking. We aimed to explore associations between ADA drug level exposure at loss of response and then at 6 and 12 months and compare these to short term clinical outcomes.

Methods

Retrospective study of adult CD patients who underwent ADA intensification to weekly dosing for secondary loss of response at three tertiary centres between 2013 and 2018. We compared trough ADA drug levels using a drug sensitive ELISA at loss of response and at 6 and 12 months after intensification with paired rates of clinical remission (Harvey Bradshaw Index <5 or Crohn’s Disease Activity Index <150), biochemical remission (C-reactive protein <5 mg/L), objective remission (CRP < 5 mg/L, faecal calprotectin < 150 µg/g or absence of inflammation at endoscopy or imaging) and ADA failure (based on Physicians Global Assessment. We performed comparisons between continuous and categorical data using Fischer’s exact or Mann–Whitney test. A receiver operated curve (ROC) analysis was used to identify target ADA levels associated with outcomes of interest.

Results

In total, 133 CD patients were included; median disease duration 8 years (IQR 4–17), 51% were biologic-exposed and 49% received concomitant immunomodulation. Rates of clinical remission, objective remission and ADA failure were 73.0%, 37.4% and 25.0% at 6 months and 65.8%, 34.0% and 42.8% at 12 months, respectively. Drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders; however increases in drug levels at 6 and 12 months were associated with improved outcomes at these time points (Figure 1). ROC analysis demonstrated that ADA drug levels 6 months after intensification > 8.9, 9.6 and 8.9 µg/ml were associated with clinical remission, objective remission and ADA non-failure respectively. Similar results were demonstrated with ADA drug levels at 12 months after dose intensification (Figure 1).

Conclusion

ADA drug levels at loss of response are not associated with subsequent 6 or 12 month outcomes. However, measurement of subsequent ADA drug levels at 6 and 12 months post escalation demonstrates that higher levels (with a target threshold between 7.7–10.9μg/ml) were associated with favourable outcomes. This study suggests that performing TDM subsequent to dose escalation of ADA has a role in predicting outcomes. Further, prospective studies dosing to target ADA drug levels are therefore needed.