Risk Factors for Rescue Therapy in Crohn’s Patients Maintained on Infliximab After Withdrawal of the Immunomodulator

A Long-Term Follow-Up

Monika Fischer, Sarah C. Campbell, Cynthia S.J. Calley, Debra Helper, Michael V. Chiorean, Hala M. Fadda

Research output: Contribution to journalArticle

Abstract

Background: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn’s disease (CD) patients and the optimal length of dual therapy are still debated. Aims: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Methods: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Results: Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6 months (range 5.4–129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4–74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95% CI 1.18–17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95% CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. Conclusions: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalDigestive Diseases and Sciences
DOIs
StateAccepted/In press - Oct 6 2017

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Immunologic Factors
Crohn Disease
Therapeutics
Infliximab
Methotrexate
Azathioprine
Proportional Hazards Models

Keywords

  • Anti-tumor necrosis factor
  • Biologic
  • Immunosuppressant
  • Inflammatory bowel disease

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Risk Factors for Rescue Therapy in Crohn’s Patients Maintained on Infliximab After Withdrawal of the Immunomodulator : A Long-Term Follow-Up. / Fischer, Monika; Campbell, Sarah C.; Calley, Cynthia S.J.; Helper, Debra; Chiorean, Michael V.; Fadda, Hala M.

In: Digestive Diseases and Sciences, 06.10.2017, p. 1-7.

Research output: Contribution to journalArticle

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abstract = "Background: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-na{\"i}ve Crohn’s disease (CD) patients and the optimal length of dual therapy are still debated. Aims: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Methods: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Results: Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6 months (range 5.4–129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4–74). Thirty-one patients (72.1{\%}) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95{\%} CI 1.18–17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95{\%} CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95{\%} CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. Conclusions: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.",
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AU - Campbell, Sarah C.

AU - Calley, Cynthia S.J.

AU - Helper, Debra

AU - Chiorean, Michael V.

AU - Fadda, Hala M.

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N2 - Background: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn’s disease (CD) patients and the optimal length of dual therapy are still debated. Aims: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Methods: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Results: Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6 months (range 5.4–129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4–74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95% CI 1.18–17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95% CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. Conclusions: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

AB - Background: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn’s disease (CD) patients and the optimal length of dual therapy are still debated. Aims: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Methods: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Results: Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6 months (range 5.4–129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0 months (range 4–74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis < 16 years versus > 40 years (HR 4.55, 95% CI 1.18–17.62, p = 0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p = 0.028), and duration of combination therapy < 6 months (HR 5.68, 95% CI 1.58, 20.36, p = 0.007) increased risk for rescue therapy. Conclusions: A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

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