Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines

Abstract

Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab

“…The concept of anti‐drug antibody elimination upon immunomodulator addition has already been demonstrated with infliximab therapy . In addition, it has recently been published that thiopurine – infliximab cotherapy in Crohn's disease patients is associated with reduced antibody formation, regardless of initial thiopurine therapeutic effect . Recapture of clinical response upon addition of an immunomodulator has also been reported among adalimumab therapy patients, who had previously failed immunomodulators, although immunogenicity and drug levels have not been evaluated in these reports.…”

“…10,31 Combination therapy of anti-TNF with an immunomodulator might result in higher drug levels and lower antibody rates, rather than post hoc addition of an immunomodulator. 24,26 Having said that, and although immunomodulator addition is successful in only roughly half of the cases, and immunosuppression carries an increased risk of infection and malignancy, [27][28][29] it still seems as a worthwhile therapeutic strategy, especially in selected moderate to severe IBD patients who lose response to adalimumab and may have a limited arsenal of other available therapeutic options. 23,30 We attempted to identify clinical and demographic factors which would predict response to this intervention.…”

Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort

“…However, in daily practice, IBD drugs are frequently combined. Examples include the use of combined therapy with azathioprine and infliximab that has been associated with better clinical and endoscopic remission rates in CD patients naive to treatment when combined with the single use of either infliximab and azathioprine and the combined use of these substances in CD patients to reduce the risk for anti-TNF-antagonist antibody formation [9,10].…”

Can Thiopurines Prevent Formation of Antibodies Against Tumor Necrosis Factor Antagonists After Failure of These Therapies?

“…12 However, it is currently unknown whether patients who are commencing anti-TNF but have previously failed thiopurine therapy could still benefit from combination therapy through reduced immunogenicity and resultant higher drug levels. In this edition of Clinical Gastroenterology and Hepatology, Bar-Yoseph et al 18 present a retrospective cohort study investigating the impact of past thiopurine response and current thiopurine use on ADA formation and clinical outcome in patients with CD treated with infliximab. Across 4 centers in Israel and Belgium between 2008 and 2014, the authors identified 207 CD patients treated with 4 scheduled infliximab infusions with serial ADA levels.…”