RC Ungaro et al. Inflamm Bowel Dis 2022; 28: 649-651. Impact of Thiopurine Exposure on Immunogenicity to Infliximab Is Negligible in the Setting of Elevated Infliximab Concentrations

Background: Whether proactive therapeutic drug monitoring (pTDM) is superior to reactive TDM (rTDM) is not entirely clear, though some studies have shown better outcomes with pTDM. Additionally, Colombel et al (Clin Gastroenterol Hepatol 2019; 17: 1525-32) showed that antidrug antibodies during combination therapy were detected only in those with the lowest quartile of infliximab trough levels; this suggests that optimized monotherapy should be similarly effective to combination therapy.

Methods: The authors retrospectively analyzed a commercial laboratory database (Prometheus) with 3970 patients and paired 6-thioguanine (6-TGN) levels with infliximab (IFX) and antibodies to infliximab (ATIs)

Key findings:

• “Those with higher levels of IFX had negligible benefit from concomitant thiopurine treatment in preventing ATIs.”
• ATIs were detected in 9.9% of all patients. IFX level of >5 mcg/mL were associated with a very low risk of ATI (OR 0.05). “Immunogenicity was negligible (<3%) in the presence of IFX concentrations greater than 5 mcg/mL.”
• 6-TGN levels (>125) were associated with lower risk of ATI, OR 0.42; though, this effect had a significant impact, only for those with with IFX <5 mcg/mL.
• The authors note the prospective OPTIMIZE study (NCT04835506) should help determine the effectiveness of pTDM.

My take: In patients with IFX levels >5 mcg/mL, there does not appear to be much benefit for most patients from the addition of a thiopurine; this may not be true for those who are switching to a 2nd anti-TNF agent due to antidrug antibodies. This study supports pTDM to assure adequate IFX levels.

Related blog posts:

• Combination Therapy Study Points to Central Role of Adequate Drug Levels
• Can Therapeutic Drug Monitoring with Monotherapy Achieve Similar Results as Combination Therapy in IBD?
• Low Anti-TNF Levels or Antibodies Are Associated with Antibodies to Subsequent Anti-TNF Agent
• For Next Insurance Appeal: TDM for Adalimumab & Satire on PA
• Here’s the Proof That Proactive Therapeutic Drug Monitoring Improves Outcomes in Children with Crohn’s Disease
• Immune-Mediated Reactions to Anti-TNFs and What to Do About Them
• Better Levels –>Better Outcomes with Adalimumab
• “Do Not Stop Anti-TNF Medications in Children with IBD When They Are Working”
• What about Combination Therapy with Adalimumab?
• Digging into the COMMIT study

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