Anti-Drug Antibodies May Affect RA Treatment

Physicians commonly prescribe different tumor necrosis factor (TNF) inhibitors to treat rheumatoid arthritis (RA). Etanercept is a soluble TNF receptor; whereas, adalimumab and infliximab are anti-TNF monoclonal antibodies. New research performed by Robert J. Moots, PhD, FRCP, a professor of rheumatology at the University of Liverpool in the U.K., and colleagues has found anti-drug antibodies (ADAs) in adalimumab- and infliximab-treated patients, but not in etanercept-treated patients. The findings were published online April 27 in Plos One.¹

The multi-national study had a cross-sectional design and did not include interventions. It focused on patients with RA who received treatment for 6–24 months and recruited only those who were still responding reasonably well to a given drug treatment and, thus, were still being prescribed that treatment.

“To our knowledge, this was the first time that [ADA] levels [for] etanercept, adalimumab and infliximab were assessed in a single study using clinical samples from the same patient population, the same methodology, the same laboratory and the same clinical data to evaluate information from a real-world clinical practice setting,” write the authors in their discussion. “This is important to ensure accurate and meaningful comparison of responses [to] the individual therapeutic agents.”

The study included 595 patients (etanercept=200, adalimumab=199 and infliximab=196), all with similar baseline demographics. The mean duration of treatment was 14.6 months (etanercept), 13.5 months (adalimumab) and 13.1 months (infliximab). The treatment doses for all of the drugs were within the approved prescribing ranges.

Patients tolerated all three TNF inhibitors, and only patients receiving the anti-TNF monoclonal antibodies tested positive for ADA. Although none of the patients treated with etanercept had detectable ADA levels, 24.4% of patients in the pooled adalimumab/infliximab group had detectable ADA levels. Specifically, 31.2% of patients treated with adalimumab and 17.4% of patients treated with infliximab tested positive for ADAs.

When the investigators pooled data from all three TNF inhibitors, they found that 61.1% of patients were in low disease activity (LDA) and 44.1% of patients were in remission. A significantly higher proportion of patients without detectable ADAs (46.7%) than those with detectable ADAs (30.9%) were in remission. Additionally, in the adalimumab- and infliximab-treated groups, patients with detectable ADAs had significantly lower serum trough drug concentrations—80.5% lower in patients treated with adalimumab and 98% lower in patients treated with infliximab. Patients with detectable ADAs also had higher serum levels of the inflammation markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In addition, the investigators tested composite efficacy measures of Disease Activity Scores (DAS) based on 28-joint count (DAS28) combined with CRP (DAS28-CRP), as well as DAS28-ESR. They found a statistically negative correlation of serum trough drug concentration and these composite efficacy measures, as well as the single efficacy measures of 28 tender joint count, ESR and CRP concentrations in adalimumab-treated patients. Thus, patients without ADAs tended to have a numerically better clinical outcome than those with ADAs.

The researchers then examined patient-reported outcomes and, surprisingly, found no differences between serum trough drug concentration and those outcomes in patients treated with etanercept or infliximab. However, patients treated with adalimumab did have a statistically significant negative correlation between serum trough drug concentration and Health Assessment Questionnaire Disability Index. The investigators suggested that these finding may be a reflection of their study design, in which patients were recruited only if they were satisfied with their given treatment.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Moots RJ, Xavier RM, Mok CC, et al. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study. PLoS One. 2017 Apr 27;12(4):e0175207. doi: 10.1371/journal.pone.0175207. eCollection 2017.