Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease

Victoria Grossi; Trudy Lerer; Anne Griffiths; Neal LeLeiko; Jose Cabrera; Anthony Otley; James Rick; David Mack; Athos Bousvaros; Joel Rosh; Andrew Grossman; Shehzaad Saeed; Marsha Kay; Brendan Boyle; Maria Oliva-Hemker; David Keljo; Marian Pfefferkorn; William Faubion; Michael D. Kappelman; Boris Sudel; James Markowitz; Jeffrey S. Hyams

doi:10.1016/j.cgh.2015.04.010

Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease

Victoria Grossi, Trudy Lerer, Anne Griffiths, Neal LeLeiko, Jose Cabrera, Anthony Otley, James Rick, David Mack, Athos Bousvaros, Joel Rosh, Andrew Grossman, Shehzaad Saeed, Marsha Kay, Brendan Boyle, Maria Oliva-Hemker, David Keljo, Marian Pfefferkorn, William Faubion, Michael D. Kappelman, Boris SudelJames Markowitz, Jeffrey S. Hyams

Pediatrics - Gastro, Hepatology, Nutrition

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. Results: The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (. P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (. P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. Conclusions: In children with Crohn's disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.

Original language	English (US)
Article number	54359
Pages (from-to)	1748-1756
Number of pages	9
Journal	Clinical Gastroenterology and Hepatology
Volume	13
Issue number	10
DOIs	https://doi.org/10.1016/j.cgh.2015.04.010
State	Published - Oct 1 2015

Bibliographical note

Funding Information:
Conflicts of interest These authors disclose the following: Anne Griffiths has received research and program support from Janssen Biotech and AbbVie, has served as a consultant for Janssen Biotech, AbbVie, Receptos, Nestle, and Ferring, and has been a speaker for AbbVie; Anthony Otley has served on the advisory boards of Janssen Canada and Nestle, and has received education and research grants from Janssen Canada, AbbVie, and Nestle; David Mack has served on the advisory boards of AbbVie and Janssen Biotech, and has received an education grant from AbbVie; Athos Bousvaros has received research support from Prometheus, and has served as a consultant for Takeda/Millenium, Cubist, Dyax, and Peabody Arnold; Joel Rosh has served as a consultant for AbbVie and Janssen Biotech, has received research support from AbbVie, Janssen Biotech, and Astra Zeneca, has served as a consultant for Soligenix and Receptos, and has served on the speaker’s bureau for Prometheus; Shehzad Saeed has served on the speaker’s bureau for AbbVie; Maria Oliva-Hemker has served as a consultant and received research support from AbbVie; William Faubion has served as a consultant for Janssen Biotech, AbbVie, Shire, and Genentech, and has served on the advisory board for UCB; Michael Kappelman has served as a consultant for and received research support from Janssen Biotech and AbbVie; James Markowitz has served on the advisory boards of Janssen Biotech, AbbVie, and UCB, and has served as a consultant for Receptos and Soligenix; Jeffrey Hyams has served on the advisory boards of Janssen Biotech, AbbVie, UCB, and Takeda, has received research support from Janssen Biotech, has served on the speaker’s bureau for Janssen Biotech, and has served as a consultant for Soligenix, Receptos, Celgene, and Avaxia.

Publisher Copyright:
© 2015.

Keywords

Anti-Tumor Necrosis Factor
IBD
Immunosuppressant
TNF

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Grossi, V., Lerer, T., Griffiths, A., LeLeiko, N., Cabrera, J., Otley, A., Rick, J., Mack, D., Bousvaros, A., Rosh, J., Grossman, A., Saeed, S., Kay, M., Boyle, B., Oliva-Hemker, M., Keljo, D., Pfefferkorn, M., Faubion, W., Kappelman, M. D., ... Hyams, J. S. (2015). Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease. Clinical Gastroenterology and Hepatology, 13(10), 1748-1756. Article 54359. https://doi.org/10.1016/j.cgh.2015.04.010

Grossi, V, Lerer, T, Griffiths, A, LeLeiko, N, Cabrera, J, Otley, A, Rick, J, Mack, D, Bousvaros, A, Rosh, J, Grossman, A, Saeed, S, Kay, M, Boyle, B, Oliva-Hemker, M, Keljo, D, Pfefferkorn, M, Faubion, W, Kappelman, MD, Sudel, B, Markowitz, J & Hyams, JS 2015, 'Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease', Clinical Gastroenterology and Hepatology, vol. 13, no. 10, 54359, pp. 1748-1756. https://doi.org/10.1016/j.cgh.2015.04.010

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title = "Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease",

abstract = "It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. Results: The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (. P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (. P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. Conclusions: In children with Crohn's disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.",

keywords = "Anti-Tumor Necrosis Factor, IBD, Immunosuppressant, TNF",

author = "Victoria Grossi and Trudy Lerer and Anne Griffiths and Neal LeLeiko and Jose Cabrera and Anthony Otley and James Rick and David Mack and Athos Bousvaros and Joel Rosh and Andrew Grossman and Shehzaad Saeed and Marsha Kay and Brendan Boyle and Maria Oliva-Hemker and David Keljo and Marian Pfefferkorn and William Faubion and Kappelman, {Michael D.} and Boris Sudel and James Markowitz and Hyams, {Jeffrey S.}",

note = "Funding Information: Conflicts of interest These authors disclose the following: Anne Griffiths has received research and program support from Janssen Biotech and AbbVie, has served as a consultant for Janssen Biotech, AbbVie, Receptos, Nestle, and Ferring, and has been a speaker for AbbVie; Anthony Otley has served on the advisory boards of Janssen Canada and Nestle, and has received education and research grants from Janssen Canada, AbbVie, and Nestle; David Mack has served on the advisory boards of AbbVie and Janssen Biotech, and has received an education grant from AbbVie; Athos Bousvaros has received research support from Prometheus, and has served as a consultant for Takeda/Millenium, Cubist, Dyax, and Peabody Arnold; Joel Rosh has served as a consultant for AbbVie and Janssen Biotech, has received research support from AbbVie, Janssen Biotech, and Astra Zeneca, has served as a consultant for Soligenix and Receptos, and has served on the speaker{\textquoteright}s bureau for Prometheus; Shehzad Saeed has served on the speaker{\textquoteright}s bureau for AbbVie; Maria Oliva-Hemker has served as a consultant and received research support from AbbVie; William Faubion has served as a consultant for Janssen Biotech, AbbVie, Shire, and Genentech, and has served on the advisory board for UCB; Michael Kappelman has served as a consultant for and received research support from Janssen Biotech and AbbVie; James Markowitz has served on the advisory boards of Janssen Biotech, AbbVie, and UCB, and has served as a consultant for Receptos and Soligenix; Jeffrey Hyams has served on the advisory boards of Janssen Biotech, AbbVie, UCB, and Takeda, has received research support from Janssen Biotech, has served on the speaker{\textquoteright}s bureau for Janssen Biotech, and has served as a consultant for Soligenix, Receptos, Celgene, and Avaxia. Publisher Copyright: {\textcopyright} 2015.",

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doi = "10.1016/j.cgh.2015.04.010",

language = "English (US)",

volume = "13",

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T1 - Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease

AU - Grossi, Victoria

AU - Lerer, Trudy

AU - Griffiths, Anne

AU - LeLeiko, Neal

AU - Cabrera, Jose

AU - Otley, Anthony

AU - Rick, James

AU - Mack, David

AU - Bousvaros, Athos

AU - Rosh, Joel

AU - Grossman, Andrew

AU - Saeed, Shehzaad

AU - Kay, Marsha

AU - Boyle, Brendan

AU - Oliva-Hemker, Maria

AU - Keljo, David

AU - Pfefferkorn, Marian

AU - Faubion, William

AU - Kappelman, Michael D.

AU - Sudel, Boris

AU - Markowitz, James

AU - Hyams, Jeffrey S.

N1 - Funding Information: Conflicts of interest These authors disclose the following: Anne Griffiths has received research and program support from Janssen Biotech and AbbVie, has served as a consultant for Janssen Biotech, AbbVie, Receptos, Nestle, and Ferring, and has been a speaker for AbbVie; Anthony Otley has served on the advisory boards of Janssen Canada and Nestle, and has received education and research grants from Janssen Canada, AbbVie, and Nestle; David Mack has served on the advisory boards of AbbVie and Janssen Biotech, and has received an education grant from AbbVie; Athos Bousvaros has received research support from Prometheus, and has served as a consultant for Takeda/Millenium, Cubist, Dyax, and Peabody Arnold; Joel Rosh has served as a consultant for AbbVie and Janssen Biotech, has received research support from AbbVie, Janssen Biotech, and Astra Zeneca, has served as a consultant for Soligenix and Receptos, and has served on the speaker’s bureau for Prometheus; Shehzad Saeed has served on the speaker’s bureau for AbbVie; Maria Oliva-Hemker has served as a consultant and received research support from AbbVie; William Faubion has served as a consultant for Janssen Biotech, AbbVie, Shire, and Genentech, and has served on the advisory board for UCB; Michael Kappelman has served as a consultant for and received research support from Janssen Biotech and AbbVie; James Markowitz has served on the advisory boards of Janssen Biotech, AbbVie, and UCB, and has served as a consultant for Receptos and Soligenix; Jeffrey Hyams has served on the advisory boards of Janssen Biotech, AbbVie, UCB, and Takeda, has received research support from Janssen Biotech, has served on the speaker’s bureau for Janssen Biotech, and has served as a consultant for Soligenix, Receptos, Celgene, and Avaxia. Publisher Copyright: © 2015.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. Results: The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (. P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (. P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. Conclusions: In children with Crohn's disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.

AB - It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. Results: The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (. P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (. P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. Conclusions: In children with Crohn's disease, concomitant treatment with an immunomodulator for more than 6 months after starting infliximab therapy increases the chances that patients will remain on infliximab. In boys, methotrexate appears to increase the durability of infliximab therapy compared with thiopurine.

KW - Anti-Tumor Necrosis Factor

KW - IBD

KW - Immunosuppressant

KW - TNF

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Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease

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