P339 Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with Inflammatory Bowel Disease

Abstract

Abstract Background The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. Methods Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The cut off of therapeutic TLs for both IFX and ADAs was, 5μg/ml. For anti-drug antibodies the cut off of, 10 AU/ml for IFX and, 3 AU/ml for ADA (as positivity of anti-drug antibodies was defined) was applied. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. Results A total of, 102 IBD patients [mean age (SD), 43.4 (13.8) years, females, 40 (39%), Crohn’s Disease, 85 (84%), under IFX, 50 (49%), under combination therapy with immunomodulator, 36 (35%), median duration of treatment (IQR), 33 (21–81.8) months] were included. Among them, 53 (52%) were ANA positive with, 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity (ANA greater than, 1:80) was found to be correlated with age (P=0.008), female gender (P=0.03), duration of treatment (P=0.06), arthralgias (P=0.04) and TLs (P=0.007). In multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P=0.04 and P=0.003 respectively). Studying separately IFX and ADA treated patients, the median IFX TLs of ANA(+) group (N=28) was, 3.51 (1.2–7.12) μg/ml significantly lower than the median IFX TLs of ANA(-) group [7.38 (4.83–10.3) μg/ml, N=22], P=0.017. The median antibodies to IFX of ANA(+) group was, 2.65 (2.4–3.24) AU/ml, significantly higher than the median antibodies to IFX of ANA(-) group [2.53 (2.11–2.83) AU/ml, P=0.03]. Regarding ADA treated patients, the median TLs of ANA(+) and ANA(-) group was, 7.33 (2.03–9.85) VS, 9.32 (6.17–10.05) μg/m (P=0.14), while antibodies to ADA in ANA(+) and ANA(-) group was, 1.42 (1.40–1.43) VS, 1.41 (1.40–1.43) AU/ml (P=0.52). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. Conclusion In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs, more remarkably with IFX TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.