Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure
Bella Ungar, Ola Haj-Natour, Uri Kopylov, Miri Yavzori, Ella Fudim, Orit Picard, Ronen Loebstein, Adi Lahat, Yaakov Maor, Benjamin Avidan, Alon Lang, Batia Weiss, Yehuda Chowers, Rami Eliakim, Shomron Ben-Horin*
Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P=0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P=0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P=0.002; OR 0.42 95% CI 0.18-0.99, p=0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p=0.04, OR 4.45 95% CI 1.2-16.6, p=0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p=0.04). P=0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P=0.04; OR 4.45, 95% CI 1.2-16.6, P=0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P=0.04). Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.
Medicine (United States)
https://doi.org/10.1097/MD.0000000000000673
10.1097/MD.0000000000000673
Dive into the research topics of 'Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure'. Together they form a unique fingerprint.
Infliximab Medicine & Life Sciences 100%
Antibody Formation Medicine & Life Sciences 76%
Antibodies Medicine & Life Sciences 25%
Inflammatory Bowel Diseases Medicine & Life Sciences 23%
Crohn Disease Medicine & Life Sciences 9%
Ungar, B., Haj-Natour, O., Kopylov, U., Yavzori, M., Fudim, E., Picard, O., Loebstein, R., Lahat, A., Maor, Y., Avidan, B., Lang, A., Weiss, B., Chowers, Y., Eliakim, R., & Ben-Horin, S. (2015). Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure. Medicine (United States), 94(18), [e673]. https://doi.org/10.1097/MD.0000000000000673
Ungar, Bella ; Haj-Natour, Ola ; Kopylov, Uri et al. / Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure. In: Medicine (United States). 2015 ; Vol. 94, No. 18.
@article{b3faf10af99e4dd9b49e88714ded36e0,
title = "Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure",
abstract = "Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P=0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P=0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P=0.002; OR 0.42 95% CI 0.18-0.99, p=0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p=0.04, OR 4.45 95% CI 1.2-16.6, p=0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p=0.04). P=0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P=0.04; OR 4.45, 95% CI 1.2-16.6, P=0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P=0.04). Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.",
author = "Bella Ungar and Ola Haj-Natour and Uri Kopylov and Miri Yavzori and Ella Fudim and Orit Picard and Ronen Loebstein and Adi Lahat and Yaakov Maor and Benjamin Avidan and Alon Lang and Batia Weiss and Yehuda Chowers and Rami Eliakim and Shomron Ben-Horin",
note = "Publisher Copyright: {\textcopyright} 2015 Wolters Kluwer Health, Inc.",
doi = "10.1097/MD.0000000000000673",
journal = "Medicine",
Ungar, B, Haj-Natour, O, Kopylov, U, Yavzori, M, Fudim, E, Picard, O, Loebstein, R, Lahat, A, Maor, Y, Avidan, B, Lang, A, Weiss, B, Chowers, Y, Eliakim, R & Ben-Horin, S 2015, 'Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure', Medicine (United States), vol. 94, no. 18, e673. https://doi.org/10.1097/MD.0000000000000673
Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure. / Ungar, Bella; Haj-Natour, Ola; Kopylov, Uri et al.
In: Medicine (United States), Vol. 94, No. 18, e673, 01.01.2015.
T1 - Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure
AU - Ungar, Bella
AU - Haj-Natour, Ola
AU - Kopylov, Uri
AU - Yavzori, Miri
AU - Fudim, Ella
AU - Picard, Orit
AU - Loebstein, Ronen
AU - Lahat, Adi
AU - Maor, Yaakov
AU - Avidan, Benjamin
AU - Lang, Alon
AU - Weiss, Batia
AU - Chowers, Yehuda
AU - Eliakim, Rami
N1 - Publisher Copyright: © 2015 Wolters Kluwer Health, Inc.
N2 - Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P=0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P=0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P=0.002; OR 0.42 95% CI 0.18-0.99, p=0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p=0.04, OR 4.45 95% CI 1.2-16.6, p=0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p=0.04). P=0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P=0.04; OR 4.45, 95% CI 1.2-16.6, P=0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P=0.04). Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.
AB - Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P=0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P=0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P=0.002; OR 0.42 95% CI 0.18-0.99, p=0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p=0.04, OR 4.45 95% CI 1.2-16.6, p=0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p=0.04). P=0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P=0.04; OR 4.45, 95% CI 1.2-16.6, P=0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P=0.04). Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.
U2 - 10.1097/MD.0000000000000673
DO - 10.1097/MD.0000000000000673
JO - Medicine
JF - Medicine
M1 - e673
Ungar B, Haj-Natour O, Kopylov U, Yavzori M, Fudim E, Picard O et al. Ashkenazi jewish origin protects against formation of antibodies to infliximab and therapy failure. Medicine (United States). 2015 Jan 1;94(18):e673. doi: 10.1097/MD.0000000000000673