Antidrug antibodies may contribute to TNF inhibitor failure in arthritis patients
medwireNews: The development of antidrug antibodies against adalimumab or infliximab, but not etanercept, may play a role in the development of secondary treatment failure among patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA), researchers report.
Secondary failure – when patients stop responding to treatment following an initial response – occurs in up to 30% of patients with inflammatory arthritis, and may happen due to “the development of anti-drug antibodies, which can neutralize the drug or decrease the serum drug concentrations to sub-therapeutic levels,” explain Alejandro Balsa (Hospital Universitario La Paz, Madrid, Spain) and study co-authors.
The team carried out a cross-sectional study of 570 patients with inflammatory arthritis (276 with RA and 294 with SpA) who experienced secondary treatment failure during tumor necrosis factor (TNF) inhibitor therapy. In all, 38.1% of participants were treated with adalimumab, while 33.0% and 28.9% received infliximab and etanercept, respectively.
A fifth of all patients developed antidrug antibodies, with 29.3% testing positive for antibodies to adalimumab and 27.3% having antibodies to infliximab. However, none of the etanercept-treated patients had antidrug antibodies.
The majority of patients who had antidrug antibodies had no detectable drug levels in the serum, at 82.5% for adalimumab-treated patients, and 78.4% of those with secondary failure to infliximab.
“The development of [antidrug antibodies], therefore, appears to be a major contributor to reduced serum drug concentrations and, consequently, secondary treatment failure in this population,” write Balsa and colleagues in Rheumatology.
The researchers also found that a significantly lower proportion of patients who received DMARDs alongside TNF inhibitors developed antidrug antibodies compared with those receiving TNF inhibitor monotherapy, at 16.5% versus 26.4%.
And a significantly higher proportion of patients with SpA compared with RA had antidrug antibodies (23.8 vs 15.9%). The study authors say that the reason for this difference is “unclear,” but note that over half of the patients with SpA who had antidrug antibodies were given infliximab monotherapy, whereas the RA patients all received concomitant DMARDs, which could have influenced the results.
Although the study findings suggest that antidrug antibodies are a factor contributing to treatment failure, they are “not the only one,” remark Balsa and team.
“Other factors contributing to secondary failure potentially include compliance, obesity and monotherapy with biologics; however, these were beyond the scope of the present study and, consequently, not evaluated,” they add.
And the researchers conclude: “Further investigations could help to determine all possible causes of failure of anti-TNF therapy.”
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