Risk of subsequent anti-TNF antibodies

March 29, 2022

Issue 06

Clinical Question

Are patients who develop antibodies to one anti-TNF prone to develop antibodies to a subsequent anti-TNF?

Editor’s Bottom Line

Patients who are sensitized to an anti-TNF monoclonal antibody are significantly more likely to develop antibodies against their next anti-TNF agent. Strategies to reduce their risk of sensitization should be considered.

Reference

Casteele NV, Abreu MT, Flier S, et al. Patients with Low Drug Levels or Antibodies to a Prior Anti–Tumor Necrosis Factor Are More Likely to Develop Antibodies to a Subsequent Anti–Tumor Necrosis Factor. Clin Gastroenterol Hepatol. 2022;20(20):465–67.e2; https://www.cghjournal.org/article/fulltext

Synopsis

This retrospective case-control study included 3,616 patients with IBD treated with infliximab and then switched to adalimumab. Sixty percent of these patients had antibodies to infliximab before switching. The analysis also included 2,212 IBD patients who underwent initial treatment with adalimumab and then switched to infliximab. Thirty-six percent of these patients had antibodies to adalimumab before switching to infliximab. Most patients in both groups had Crohn’s disease.

Therapeutic drug monitoring revealed that 28.5% of those treated with infliximab first who had antibodies to infliximab subsequently developed antibodies to adalimumab. In contrast, 12.4% of those who did not have antibodies to infliximab subsequently developed antibodies to adalimumab (Odds Ratio [OR], 2.8; 95% Confidence Interval [CI], 2.4–3.4; p<0.0001). Among patients who received adalimumab before infliximab, 39.1% of patients with antibodies to adalimumab subsequently developed antibodies to infliximab, while 15.8% of those who did not initially have antibodies to adalimumab subsequently developed antibodies to infliximab (OR, 3.43; 95% CI, 2.8–4.2; p<0.0001).  

Results showed that 31.2% of those with anti-infliximab antibody concentrations ≥10 U/mL developed antibodies to adalimumab after switching to the latter drug, compared to 21.5% of those whose antibody-to-infliximab concentrations were <10 U/mL before switching to adalimumab (p<0.0001). Higher anti-adalimumab antibody concentrations were not correlated with a higher risk of developing antibodies to infliximab when adalimumab was administered before infliximab.

Serum infliximab concentrations ≤5 μg/mL were associated with subsequent development of antibodies to adalimumab (p<0.0001) and adalimumab concentrations ≤7.5 μg/mL were associated with formation of antibodies to subsequent infliximab treatment (p<0.0001).

Details

Study Design: Retrospective case-control

Funding: Therapeutic drug monitoring testing was performed by Prometheus Biosciences

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2b