Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease

Purpose 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 correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. Results One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity 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 = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. Conclusions In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

Automated summary

This study investigated the association of serum antinuclear antibodies (ANA) with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in patients with inflammatory bowel disease (IBD) receiving IFX or ADA therapy. The results showed that ANA positivity was associated with lower TLs in IBD patients receiving anti-TNF therapy, but no significant association was found with the development of cutaneous or rheumatological manifestations.