Primary nonresponse, defined as lack of clinical benefit during the induction phase, occurs in up to 30% of IBD patients treated with infliximab.
The mechanisms underlying primary nonresponse have not yet been clearly defined.
Dr Bar-Yoseph and colleagues evaluated the association of early induction infliximab and anti-infliximab antibody levels with primary nonresponse.
A retrospective observational case-control study of inflammatory bowel disease patients treated with infliximab and followed at Sheba Medical Center between 2009 and 2016 was performed.
The team measured pre-infusion infliximab and antibodies to infliximab (ATI) by previously described drug-tolerant ELISA assay.
|Antibodies to infliximab appeared more frequently in nonresponders |
|Alimentary Pharmacology & Therapeutics|
The researchers identified 35 primary nonresponders and matched with 105 primary responders.
Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders.
The team observed that antibodies to infliximab appeared more frequently, and at higher levels in nonresponders compared to responders.
Moreover, week 2 infliximab levels <6.8 μg/mL, and antibodies to infliximab levels >4.3 μg/mL-eq were predictive of primary nonresponse.
The researchers found that among the other clinical and demographic variables, higher baseline ulcerative colitis clinical score, infliximab monotherapy, prior adalimumab therapy and previous Crohn's disease-related surgeries were also associated with an increased risk of primary nonresponse.
Dr Bar-Yoseph's team concludes, "Infliximab levels below 6.8 μg/mL and antibodies to infliximab levels above 4.3 μg/mL-eq before the second infusion are associated with primary nonresponse, especially among Crohn's disease patients."