Drug Modulation Can Resolve Low-Level Anti-TNF Drug Antibodies in IBD

Low-level anti-tumor necrosis factor (TNF) anti-drug antibodies (ADAs) in patients with inflammatory bowel disease (IBD) may be overcome by dose escalation and/or addition of an immunomodulator, which can allow for clinical improvement in disease status, according to a retrospective case series of 12 patients with IBD published in the World Journal of Gastrointestinal Pharmacology and Therapeutics.

Writing in an editorial in the journal, Mansi M. Kothari, MD, and colleagues said their experience suggests that dose escalation and immunomodulation may be a viable strategy for preserving the use of an anti-TNF drug. Therapeutic drug monitoring is an important tool to guide this strategy, the researchers noted.

Their case series discusses 12 patients with IBD (8 patients had Crohn’s disease and 4 had ulcerative colitis) who had detectable but low-level ADAs after treatment with infliximab (n = 7) or adalimumab (n = 5). Disease activity in all patients was moderate to severe; median duration of disease was 8 years (range, 1 to 30). Median duration of treatment on the patients’ respective anti-TNF treatments was 18.5 months, (range, 4 to over 120).

After the presence of low-level antibodies was noted, 11 patients underwent dose escalation of the anti-TNF drug in the form of either an increase in drug frequency or dosage, and 1 patient had an immunomodulator (methotrexate) added to the treatment regimen. The researchers discussed the addition of an immunomodulator with all patients who were not already treated with one, but most patients declined because of concerns about side effects. Those who were already on immunomodulator therapy were continued on dual therapy.

Follow-up drug-level testing demonstrated resolution of ADAs in 8 patients (75%). These patients were found to have an increase in drug level (median drug levels increased to 20.2 µg/mL and 7.9 µg/mL for infliximab and adalimumab, respectively). These patients also had improvement in disease activity (decreased inflammatory markers and/or symptomatic improvement). Four patients did not have resolution of ADAs after dose escalation, and were switched to an alternate IBD therapy. These 4 patients had Crohn’s disease; it is unclear whether this fact is significant because of the small size of the study.

Prevention of immunogenicity is regarded as an important consideration in the approach to using a TNF inhibitor. “Based on this literature and our own experience as described, we believe that in certain patients, low-level anti-TNF drug antibodies can be overcome by dose escalation and/or addition of an immunomodulatory [agent], and can allow for clinical improvement in disease status,” the researchers concluded. “As the efficacy of subsequent anti-TNF drugs generally diminishes in comparison to the initial anti-TNF drug, drug manipulation to overcome low-level antibodies may be a valuable strategy to preserve the use of anti-TNFs in IBD. Therapeutic drug monitoring, which allows for measurement of drug levels and drug antibodies, is an instrumental tool to assess success or failure of this approach.”