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 Alvis Faubion, Michael D. Kappelman, Boris SudelJames Markowitz, Jeffrey S. Hyams

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Article number54359
Pages (from-to)1748-1756
Number of pages9
JournalClinical Gastroenterology and Hepatology
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2015

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Immunologic Factors
Crohn Disease
Therapeutics
Infliximab
Methotrexate

Keywords

  • Anti-Tumor Necrosis Factor
  • IBD
  • Immunosuppressant
  • TNF

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Grossi, V., Lerer, T., Griffiths, A., LeLeiko, N., Cabrera, J., Otley, A., ... 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. [54359]. https://doi.org/10.1016/j.cgh.2015.04.010

Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease. / Grossi, Victoria; Lerer, Trudy; Griffiths, Anne; LeLeiko, Neal; Cabrera, Jose; Otley, Anthony; Rick, James; Mack, David; Bousvaros, Athos; Rosh, Joel; Grossman, Andrew; Saeed, Shehzaad; Kay, Marsha; Boyle, Brendan; Oliva-Hemker, Maria; Keljo, David; Pfefferkorn, Marian; Faubion, William Alvis; Kappelman, Michael D.; Sudel, Boris; Markowitz, James; Hyams, Jeffrey S.

In: Clinical Gastroenterology and Hepatology, Vol. 13, No. 10, 54359, 01.10.2015, p. 1748-1756.

Research output: Contribution to journalArticle

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, WA, 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
Grossi, Victoria ; Lerer, Trudy ; Griffiths, Anne ; LeLeiko, Neal ; Cabrera, Jose ; Otley, Anthony ; Rick, James ; Mack, David ; Bousvaros, Athos ; Rosh, Joel ; Grossman, Andrew ; Saeed, Shehzaad ; Kay, Marsha ; Boyle, Brendan ; Oliva-Hemker, Maria ; Keljo, David ; Pfefferkorn, Marian ; Faubion, William Alvis ; Kappelman, Michael D. ; Sudel, Boris ; Markowitz, James ; Hyams, Jeffrey S. / Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease. In: Clinical Gastroenterology and Hepatology. 2015 ; Vol. 13, No. 10. pp. 1748-1756.
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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 Alvis

AU - Kappelman, Michael D.

AU - Sudel, Boris

AU - Markowitz, James

AU - Hyams, Jeffrey S.

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.

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KW - IBD

KW - Immunosuppressant

KW - TNF

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