Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis

Remo Panaccione; Subrata Ghosh; Stephen Middleton; Juan R Márquez; Boyd B Scott; Laurence Flint; Hubert J F van Hoogstraten; Annie C Chen; Hanzhe Zheng; Silvio Danese; Paul Rutgeerts

doi:10.1053/j.gastro.2013.10.052

Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis

Remo Panaccione, Subrata Ghosh, Stephen Middleton, Juan R Márquez, Boyd B Scott, Laurence Flint, Hubert J F van Hoogstraten, Annie C Chen, Hanzhe Zheng, Silvio Danese, Paul Rutgeerts

Immunology and Immunotherapy

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

523 Citations (Scopus)

Abstract

BACKGROUND & AIMS: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously.

METHODS: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached.

RESULTS: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine,compared with 22.1% (17 of 77) receiving infliximab alone(P =.017) and 23.7% (18 of 76) receiving azathioprine alone(P =.032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P =.001). Serious infections occurred in 2 patients (1 patient receiving infliximab,and 1 patient receiving azathioprine).

CONCLUSIONS: Anti–tumor necrosis factor-a–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.

Original language	English
Pages (from-to)	392-400.e3
Number of pages	12
Journal	Gastroenterology
Volume	146
Issue number	2
Early online date	25 Oct 2013
DOIs	https://doi.org/10.1053/j.gastro.2013.10.052
Publication status	Published - Feb 2014

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal
Antibodies, Monoclonal
Azathioprine
Colitis, Ulcerative
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Humans
Immunosuppressive Agents
Induction Chemotherapy
Infliximab
Infusions, Intravenous
Male
Middle Aged
Severity of Illness Index
Treatment Outcome
Young Adult
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor Inhibitors
Purine Antimetabolites
Biologic Treatment

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Panaccione, R., Ghosh, S., Middleton, S., Márquez, J. R., Scott, B. B., Flint, L., van Hoogstraten, H. J. F., Chen, A. C., Zheng, H., Danese, S., & Rutgeerts, P. (2014). Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology, 146(2), 392-400.e3. https://doi.org/10.1053/j.gastro.2013.10.052

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title = "Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis",

abstract = "BACKGROUND & AIMS: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously.METHODS: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached.RESULTS: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine,compared with 22.1% (17 of 77) receiving infliximab alone(P =.017) and 23.7% (18 of 76) receiving azathioprine alone(P =.032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P =.001). Serious infections occurred in 2 patients (1 patient receiving infliximab,and 1 patient receiving azathioprine).CONCLUSIONS: Anti–tumor necrosis factor-a–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Azathioprine, Colitis, Ulcerative, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents, Induction Chemotherapy, Infliximab, Infusions, Intravenous, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Young Adult, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Tumor Necrosis Factor Inhibitors, Purine Antimetabolites, Biologic Treatment",

author = "Remo Panaccione and Subrata Ghosh and Stephen Middleton and M{\'a}rquez, {Juan R} and Scott, {Boyd B} and Laurence Flint and {van Hoogstraten}, {Hubert J F} and Chen, {Annie C} and Hanzhe Zheng and Silvio Danese and Paul Rutgeerts",

year = "2014",

month = feb,

doi = "10.1053/j.gastro.2013.10.052",

language = "English",

volume = "146",

pages = "392--400.e3",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis

AU - Panaccione, Remo

AU - Ghosh, Subrata

AU - Middleton, Stephen

AU - Márquez, Juan R

AU - Scott, Boyd B

AU - Flint, Laurence

AU - van Hoogstraten, Hubert J F

AU - Chen, Annie C

AU - Zheng, Hanzhe

AU - Danese, Silvio

AU - Rutgeerts, Paul

PY - 2014/2

Y1 - 2014/2

N2 - BACKGROUND & AIMS: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously.METHODS: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached.RESULTS: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine,compared with 22.1% (17 of 77) receiving infliximab alone(P =.017) and 23.7% (18 of 76) receiving azathioprine alone(P =.032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P =.001). Serious infections occurred in 2 patients (1 patient receiving infliximab,and 1 patient receiving azathioprine).CONCLUSIONS: Anti–tumor necrosis factor-a–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.

AB - BACKGROUND & AIMS: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously.METHODS: This randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-a antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached.RESULTS: A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine,compared with 22.1% (17 of 77) receiving infliximab alone(P =.017) and 23.7% (18 of 76) receiving azathioprine alone(P =.032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab (P = .295) and 36.8% (28 of 76) receiving azathioprine (P =.001). Serious infections occurred in 2 patients (1 patient receiving infliximab,and 1 patient receiving azathioprine).CONCLUSIONS: Anti–tumor necrosis factor-a–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Antibodies, Monoclonal

KW - Azathioprine

KW - Colitis, Ulcerative

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Immunosuppressive Agents

KW - Induction Chemotherapy

KW - Infliximab

KW - Infusions, Intravenous

KW - Male

KW - Middle Aged

KW - Severity of Illness Index

KW - Treatment Outcome

KW - Young Adult

KW - Comparative Study

KW - Journal Article

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

KW - Tumor Necrosis Factor Inhibitors

KW - Purine Antimetabolites

KW - Biologic Treatment

U2 - 10.1053/j.gastro.2013.10.052

DO - 10.1053/j.gastro.2013.10.052

M3 - Article

C2 - 24512909

SN - 0016-5085

VL - 146

SP - 392-400.e3

JO - Gastroenterology

JF - Gastroenterology

IS - 2

ER -

Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis

Abstract

Keywords

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