Anti-Drug Antibody Incidence Risk in RA Increases Over Time With Adalimumab, Infliximab

syringe and a couple vials
syringe and a couple vials
Longer disease duration, higher baseline disease activity, and lifetime smoking were risk factors for anti-drug antibody development against adalimumab or infliximab.

In patients with rheumatoid arthritis (RA) treated with adalimumab or infliximab with methotrexate, the risk for anti-drug antibody occurrences increases over time, according to results published in Seminars in Arthritis and Rheumatism.

The results also indicated that disease duration, disease activity, and lifetime smoking were predictors of anti-drug antibody development among patients with RA.

The study included retrospective cohorts from the ABRISK database. Participants with RA (n=366) were treated with adalimumab (n=240) or infliximab (n=126); 92.4% had never been treated with anti-tumor necrosis factor (n=328) and 96.6% were co-treated with methotrexate (n=341).

The researchers used enzyme-linked immunosorbent assay to measure anti-drug antibody positivity. They estimated the cumulative incidence of anti-drug antibody and investigated potential clinical factors using Cox regression models.

Within 18 months, the researchers detected anti-drug antibodies in 19.2% (n=46) of participants treated with adalimumab and 29.4% (n=37) of those treated with infliximab.

The researchers found that the cumulative incidence of anti-drug antibody increased over time. In the adalimumab group, the incidence was 15.4% at 3 months, 17.6% at 6 months, 17.7% at 12 months, 50.0% at 15 months, and 50.0% at 18 months. For the infliximab group, the incidence was 0% at 3 months, 0% at 6 months, 34.1% at 12 months, 37.5% at 15 months, and 66.7% at 18 months.

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The researchers identified several risk factors associated with a higher risk for anti-drug antibody development, including longer disease duration (1 to 3 years vs <1 year: hazard ratio [HR] for adalimumab, 3.0; 95% CI, 1.0-8.7; HR for infliximab, 2.7; 95% CI, 1.1-6.8), moderate disease activity (28-joint Disease Activity Score 3.2-5.1 vs <3.2: HR for adalimumab, 6.6; 95% CI, 1.3-33.7), and lifetime smoking (HR for infliximab, 2.7; 95% CI, 1.2-6.3).

“Since [anti-drug antibodies] have a negative impact on clinical response and vary inversely with drug serum levels, these factors could be taken into account to tailor therapeutic drug monitoring to each patient,” the researchers wrote.

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Quistrebert J, Hassler S, Bachelet D, et al. Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: a European retrospective multicohort analysis [published online October 12, 2018]. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2018.10.006