Oral (15W173)

Evaluation of the clinical efficacy of Anti-TNF-a drug trough and antibody levels in an Irish Inflammatory bowel disease cohort

Author(s)

Donal Tighe, Shivashini Kirthi Jeyarajah, Barry Hall, Sinead Smith, Deirdre McNamara

Department(s)/Institutions

Donal Tighe, Shivashini Kirthi Jeyarajah, Barry Hall, Sinead Smith, Deirdre McNamara

Introduction

Anti-TNF-α therapies have resulted in improved IBD care. Variations in trough levels, associated with several factors including antibody status may impact outcome. Although correlation with clinical activity at a single time point is lacking, lower trough levels are associated with loss of response and clinical relapse overtime while higher trough levels are needed to achieve mucosal healing and alter disease course. As yet optimal anti-TNF trough levels are unknown and Irish data is lacking

Aims/Background

Correlate anti-TNF-α trough and antibody levels with clinical outcome over 1 year in a cohort of Irish IBD patients.

Method

In an IBD cohort with previous random anti-TNF trough and antibody levels using ELISA we performed a retrospective follow-up to assess clinical outcomes. Poor outcome was defined as; need for steroids, dose intensification, treatment discontinuation, hospitalisation and surgery. CRP was recorded. Low trough <1ug/ml, high trough 3ug/ml Infliximab and >5ug/ml Adalimumab were documented. Cut-off’s for Infliximab and Adalimumab antibodies were 2.5ug/ml and 0.45ug/ml respectively. Trough and antibody status was correlated with outcome, a p value of < 0.05 was considered significant.

Results

In all 74 patients were included, 50% (n=37) male, mean age 41 years, 57% (n=42) received Infliximab, 82.4% (n=61) had Crohn’s, mean baseline CRP 4.03. Disappointingly 27% (n=20) overall had a poor outcome, with a similar proportion in each group 24% (n=10) Infliximab and 31% (n=10) Adaluminab. A low trough occurred in only 11% (n= 8), 14.2% (n=6) Infliximab versus 6% (n=2) Adaluminab. Adalimumab antibody prevalence was greater (62.5%, n=20, versus 14.3%, n=6, p<0.001, 95% CI -0.62 to -0.22). Only 9% of Adalimumab antibodies were strongly positive. There was no difference in mean trough according to outcome (4.9ug/ml poor versus 5.4ug/ml good). Antibody positivity did not correlate with low trough levels (16.6% versus 83.3%). While 72% (n=31) on Infliximab achieved a recommended trough >3ug/ml, none on Adaluminab reached a target of >5ug/ml, p<0.0001, 95% CI 0.58- 0.90. A higher Infliximab trough was not associated with better outcomes, 3/10 poor versus 8/ 32 good response. Low infliximab trough levels did correlate with high CRP and response, mean CRP 6.66 (n=3) low trough and poor response versus 2.0 (n=24) high trough and good response (p=0.009, 95% CI -0.78 to -0.12).

Conclusions

Our study confirms loss of response is a real problem with anti-TNF therapy (27%). Our data suggests testing in relation to clinical events rather than baseline measurements may be required to optimise therapeutic monitoring.