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

Int J Colorectal Dis. 2022 Mar;37(3):639-646. doi: 10.1007/s00384-021-04091-6. Epub 2022 Jan 11.

Abstract

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.

Keywords: Anti-TNF therapy; Antinuclear antibodies; Crohn’s disease; Pharmacokinetics; Ulcerative colitis.

MeSH terms

  • Adalimumab / therapeutic use
  • Antibodies, Antinuclear* / therapeutic use
  • Female
  • Humans
  • Inflammatory Bowel Diseases* / complications
  • Infliximab / therapeutic use
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha

Substances

  • Antibodies, Antinuclear
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab