Background Since biologic therapy development, rheumatoid arthritis (RA) prognosis improves dramatically. Tumor necrosis factor alpha (TNF) is a proinflammatory cytokine that plays an important role in RA pathogenesis. Infliximab (IFX, Remicade®), is a human-murine chimerical monoclonal IgG antibody targeting TNF, approved for RA after inadequate response to conventional synthetic disease modifying antirheumatic drugs (csDMARDs).
Clinical improvement is heterogeneous with primary or secondary therapy failure. Furthermore, no factors to predict response are available in the daily practice. Detection of antibody towards IFX (ATI) was described early in the development of this drug. The hypothesis is that ATI reduce IFX concentration associated with a lack of efficacy.
Objectives To evaluate methotrexate effects on tumor necrosis factor alpha (TNF) bioactivity and antibody against infliximab (ATI) development in rheumatoid arthritis (RA) patients treated by infliximab (IFX).
Methods In a longitudinal multicenter study including 39 RA patients requiring IFX therapy, clinical data and blood sample were recorded at the inclusion (W0), at the 6th week (W6), at the 6th month (W22) and at the 12th month (W54) of treatment.
Results IFX trough level increased from W0 to W54 and distribution became heterogeneous at W22 at the time of first ATI detection. From W22, an inverse correlation between IFX trough level and ATI concentrations was observed (p<0.05). ATI concentrations inversely correlated with EULAR response at W22 (p<0.005). TNF bioactivity decreased from W0 to W6, and distribution was heterogeneous from W22. TNF bioactivity correlated with both DAS28 (p<0.05) and ATI concentrations (p<0.001) at W22. Methotrexate therapy was associated with absence of ATI at W22 (p<0.05), and TNF bioactivity was lower than in patients with other synthetic disease modifying antirheumatic drugs (p<0.005).
Conclusions This suggests that methotrexate plays a key role on TNF bioactivity and against ATI development
Disclosure of Interest None declared