Infliximab Antibodies Formation Differs in Children with Uveitis, Refractory Arthritis

In adults with rheumatic disease, development of antibodies to the tumor necrosis factor-α-inhibitor infliximab (Remicade/Janssen) is associated with infusion reactions, as well as absence of clinical response. However, in children with rheumatic disease, few data have been available on the immunogenicity of infliximab or the clinical features associated with its immunogenicity.

To fill this data gap, a team of Swiss researchers evaluated 62 children with arthritis, uveitis, or both refractory to standard treatment and, therefore, treated with infliximab at the Department of Rheumatology at University Children’s Hospital in Zurich, Switzerland, between August 2009 and August 2012.

The team collected blood samples from patients six months before initiation of infliximab infusions and every six months thereafter. They then tested the samples for anti-infliximab antibodies by using a radioimmunoassay.

In addition, the researchers retrospectively reviewed patients’ charts for clinical features that could be associated with infliximab immunogenicity and determined whether those features correlated with the presence of anti-infliximab antibodies in the samples.

After a mean treatment period of 1,084 days (range: 73 to 3,498 days), the researchers found anti-infliximab antibodies in 14 of 62 children (23%). However, during continued infliximab treatment, anti-infliximab antibodies disappeared in seven of 14 children (50%). The investigators noted infusion reactions in 10 of the 62 patients (16%) during continued treatment with infliximab.

Not surprisingly, bivariate analysis revealed a particularly strong association between the development of anti-infliximab antibodies and infusion reactions (Odds Ratio (OR), 15). The analysis also revealed that the development of anti-infliximab antibodies was associated with being younger when infliximab therapy was started (7 years old vs. 10 years old, P = 0.003).

In contrast, anti-infliximab antibodies were less likely to develop in patients with uveitis as a treatment indication than in those with arthritis as a treatment indication (OR, 0.17). This association probably resulted because higher doses of infliximab were used for arthritis than for uveitis, according to the team.

After multivariate logistic regression analysis, the associations between the development of anti-infliximab antibodies and all three covariates were still highly significant.

These findings led the team to conclude that anti-infliximab antibodies were associated with infusion reactions, younger age at initiation of infliximab treatment, and arthritis as a treatment indication. They also concluded that anti-infliximab antibodies were common findings at any time during infliximab treatment. Such antibodies were present in nearly one-quarter of patients at some point during the course of the treatment.

The study, “Prevalence of anti-infliximab antibodies and their associated co-factors in children with refractory arthritis and/or uveitis: a retrospective longitudinal cohort study,” was published in the January 2017 issue of The Journal of Rheumatology.

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