Infliximab exposure, clinical response, and inflammatory biomarkers in
patients with rheumatoid arthritis: a descriptive study
Abstract
Aim: The anti-TNF antibody Infliximab (IFX) has therapeutic efficacy in
rheumatoid arthritis (RA). However, some patients do not respond. We
aimed to identify factors associated with IFX exposure, of clinical
response, and of the response at immunologic level. Methods: We
performed a prospective observational study of repeated measures in
patients with RA treated with IFX from July 2014 to August 2020 at
Bellvitge University Hospital. For IFX exposure, we measured IFX trough
concentrations (Cmin), and antibodies towards IFX (ATI). For the
clinical response we evaluated the Disease Activity Score-28 for
Rheumatoid Arthritis using erythrocyte sedimentation rate (ESR)
(DAS28-ESR) and C-reactive protein (CRP) (DAS28-CRP). For the
immunologic response, we determined total serum concentration of TNF,
and IL-6. Finally, we performed a mixed-effects analysis to determine
factors associated with IFX Cmin, clinical response and IL-6 and TNF
concentrations. Results: We collected a total of 120 samples
cor-responding to 22 patients. IFX Cmin were associated with ATI
presence and serum IL-6. DAS28-ESR was associated with sex, ESR, CRP,
and serum IL-6 influenced DAS28-ESR. Finally, IL-6 concentration was
associated with ESR and CRP, and TNF concentration with CRP, IFX Cmin,
and IL-6 concentration. Conclusions: IFX Cmin was highly associated with
the presence of ATI. IFX Cmin significantly contributed to TNF serum
concentrations in patients with undetectable ATI and IL-6 concentration,
which in turn was associated with serum TNF and DAS28-ESR score.
Additional population pharmacockinetic analysis with rich sampling are
warranted to confirm our results.