Anti-drug antibodies (ADAs) to biologic therapies contribute to the loss of response and infusion reactions to anti-TNF drugs in patients with inflammatory bowel disease (IBD).
The reasons behind this immunogenicity are complex, and have not been the focus of a dedicated review for prescribers.
Dr Moss and colleagues from Massachusetts, USA provided an overview of the patient, product and prescriber factors, which have been associated with the immunogenicity of anti-TNF therapy, and draw conclusions for clinical practice.
Review of representative observational studies and clinical trials from the IBD and other literature, which report associations with ADA development, with a focus on infliximab and adalimumab.
|Drug mishandling can induce immunogenic protein aggregates|
|Alimentary Pharmacology & Therapeutics|
ADAs develop in 10–20% of patients receiving anti-TNF maintenance therapy, and these patients are 3 times more likely to lose response as ADA-negative patients.
The research team found that patient genotype plays a role in ADA risk in a minority of patients, but age or disease type is not a major factor.
Drug mishandling, such as agitation or freeze–thaw cycles, can induce protein aggregates, which are known to be immunogenic.
The researchers observed that prescription of maintenance therapy with concomitant immunomodulators, and achieving suitable trough drug levels, reduces the risk of ADAs in patients with IBD.
Dr Moss' team concludes, "Patients and prescribers can take several steps to reduce the risk of development of anti-drug antibodies to anti-TNF antibodies."
"Further research is required to determine if immunogenic factors identified in other situations apply to use of anti-TNFs in IBD."