TY - JOUR
T1 - Early drug and anti-infliximab antibody levels for prediction of primary nonresponse to infliximab therapy
AU - Bar-Yoseph, H.
AU - Levhar, N.
AU - Selinger, L.
AU - Manor, U.
AU - Yavzori, M.
AU - Picard, O.
AU - Fudim, E.
AU - Kopylov, U.
AU - Eliakim, R.
AU - Ben-Horin, S.
AU - Chowers, Y.
AU - Ungar, B.
N1 - Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2018/1
Y1 - 2018/1
N2 - Background: 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. Aim: To evaluate the association of early (week 2 and week 6) induction infliximab and anti-infliximab antibody levels with primary nonresponse. Methods: 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. Pre-infusion infliximab and antibodies to infliximab (ATI) levels were measured by our previously described drug-tolerant ELISA assay. Results: Thirty-five primary nonresponders have been identified and matched with 105 primary responders (1:3 ratios). Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders (week 2, 6: median level 7.2, 2.2 μg/mL vs 13.5, 9.5 μg/mL, P =.0019, P <.0001 respectively). Antibodies to infliximab appeared more frequently (either week 2 or 6, 68% vs 28% prevalence, P =.0004) and at higher levels in nonresponders compared to responders (week 2, 6: median ATI 7.3, 10.8 μg/mL-eq vs 3.8, 4.4 μg/mL-eq, P =.005, P =.008 respectively). Moreover, week 2 infliximab levels <6.8 μg/mL (AUC = 0.68, P =.002, sensitivity 50%, specificity 86%) and antibodies to infliximab levels >4.3 μg/mL-eq (AUC = 0.78, P =.0004, sensitivity 77%, specificity 71%) were predictive of primary nonresponse. 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. Conclusions: 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.
AB - Background: 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. Aim: To evaluate the association of early (week 2 and week 6) induction infliximab and anti-infliximab antibody levels with primary nonresponse. Methods: 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. Pre-infusion infliximab and antibodies to infliximab (ATI) levels were measured by our previously described drug-tolerant ELISA assay. Results: Thirty-five primary nonresponders have been identified and matched with 105 primary responders (1:3 ratios). Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders (week 2, 6: median level 7.2, 2.2 μg/mL vs 13.5, 9.5 μg/mL, P =.0019, P <.0001 respectively). Antibodies to infliximab appeared more frequently (either week 2 or 6, 68% vs 28% prevalence, P =.0004) and at higher levels in nonresponders compared to responders (week 2, 6: median ATI 7.3, 10.8 μg/mL-eq vs 3.8, 4.4 μg/mL-eq, P =.005, P =.008 respectively). Moreover, week 2 infliximab levels <6.8 μg/mL (AUC = 0.68, P =.002, sensitivity 50%, specificity 86%) and antibodies to infliximab levels >4.3 μg/mL-eq (AUC = 0.78, P =.0004, sensitivity 77%, specificity 71%) were predictive of primary nonresponse. 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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85033471420&partnerID=8YFLogxK
U2 - 10.1111/apt.14410
DO - 10.1111/apt.14410
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C2 - 29124774
AN - SCOPUS:85033471420
SN - 0269-2813
VL - 47
SP - 212
EP - 218
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 2
ER -