Immunogenicity of antitumor necrosis factor therapy in patients with spondyloarthritis

Abstract

ObjectivesTo evaluate the serum dosage of the biomedicine (DBM) and the incidence of antidrug antibody (ADA) against antitumor necrosis factor (TNF) in spondyloarthritis, and to demonstrate the influence of these parameters on the clinical efficiency.MethodsWe conducted a cross-sectional multicentric study including patients with spondylarthritis (SpA) under antiTNF (infliximab [INF], etanercept [ETA] and adalimumab [ADL]) for at least 6 months. A dosage of the ADA and DBM were practiced by the immuno-enzymatic essay.ResultSeventy one patients were recruited. Disease modifying antirheumatic drugs (DMARDs) were associated with anti-TNF in 30%. ADA was positive in 54% for INF, 33% for ADL and 0% for ETA with a significant difference(p<0.0001). Immunogenicity was correlated to a bad therapeutic response (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]≥4)(p=0.04). The DBM was inversely correlated with the rate of ADA for patients treated with INF(p<0.0001) and ADL(p<0.0001). The DBM was also inversely correlated with BASDAI of INF(p=0.03) and ADL (p=0.01). ADA was significantly associated with an anterior switch of anti TNF(p=0.04), the use of INF(p=0.002), presence of coxitis(p=0.01) and higher body mass index (BMI)(p=0.007). DMARDs associated with anti TNF were not a protective factor for positive ADA. In a multivariate study, only INF and BMI were independent factors of positive ADA.ConclusionThe ADA formation lowered the DBM and favored the therapeutic failure.

No correlation between anti-drug antibodies and therapeutic response in Tunisian patients with chronic inflammatory diseases treated by TNF blockers

“…In the different group of our study, RA, SpA and CD, the presence of ADAbs was inversely correlated to the trough levels of IFX and ADA. Similar data have been reported in a large number of studies in the literature [1,3,17,[23][24][25][26][27][28][29][30][31][32][33].…”

“…Our results showed that IFX was the most immunogenic biologic (40%) compared to ADA (25%), without a statistically significant difference. Several authors agree that IFX is more immunogenic than ADA [16,17]. This could be explained by the fact that ADA, being a human antibody, is less likely to form ADAbs than IFX which is a chimeric antibody [4].…”

Treatment Strategies for Patients With Immune-Mediated Inflammatory Diseases

“…TDM may help improve the effectiveness of infliximab, a murine monoclonal antibody for which development of ADAs is relatively common. ADAs may develop in 15% to 50% of patients . ADAs may contribute to infusion reactions, subtherapeutic drug levels, and reduced effectiveness …”

“…In the study by Syversen et al, at 30-week follow-up, the primary end point of clinical remission was achieved in 50.5% (100/198) of patients in the TDM group and in 53% (106/200) of patients in the standard therapy group, with no significant difference between groups. ADA formation in this cohort of patients with mixed disease indications was relatively low (17%-18%), in contrast to other studies in which it was as high as 50% in patients with RA and axial spondyloarthritis, especially among those who did not receive concomitant immunomodulators such as methotrexate …”