Anti-TNF-associated immunogenicity: use a retroactive drug but a proactive approach

Correspondence to Dr Ashish Srinivasan, Department of Gastroenterology, Eastern Health, Box Hill, VIC 3128, Australia; ashish.srinivasan@monash.edu We read the study by Roblin et al with interest.1 Given that prior antitumour necrosis factor (anti-TNF) monotherapy failure is frequently associated with antibody development to a second anti-TNF within 24 months,2 it is our practice, to (re)introduce immunomodulator cotherapy with the second anti-TNF to reduce immunogenicity and improve treatment persistence.3 4 Roblin et al’s findings support this concept, reinforcing the value of thiopurine cotherapy to reduce immunogenicity with the second anti-TNF following immune-mediated failure of first-line anti-TNF monotherapy. [...]they demonstrated that combination therapy was less frequently associated with clinical relapse, clinical failure and pharmacokinetic failure (ie, undetectable anti-TNF trough levels with high antidrug antibodies) than anti-TNF monotherapy. [...]we question how long Roblin et al would continue combination therapy in those ‘at risk’ of immunogenicity, and whether (and how) dose-reduction or cessation of immunomodulator cotherapy would be undertaken. [...]while this study sought to evaluate the comparative effectiveness of a ‘set and forget’ strategy of anti-TNF monotherapy versus combination therapy, future studies should go one step further by incorporating active decision making and early therapeutic optimisation in response to subclinical inflammation associated with unfavourable pharmacokinetics, thence determining whether such a strategy can mitigate clinical failure altogether.