Original article—alimentary tract
Induction and Maintenance Therapy With Infliximab for Children With Moderate to Severe Ulcerative Colitis

https://doi.org/10.1016/j.cgh.2011.11.026Get rights and content

Background & Aims

We evaluated the efficacy and safety of infliximab for inducing and maintaining benefit in children with moderately to severely active ulcerative colitis (UC).

Methods

Patients (6–17 years old) who had active UC (Mayo scores of 6–12; endoscopic subscores ≥2) and had not responded to or tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and 6. The primary end point was response at week 8 (decreases in Mayo scores ≥30% and ≥3 points and decreases in rectal bleeding subscores of ≥1 or an absolute subscore of ≤1). At week 8, only responders were randomly assigned to groups given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54. Maintenance end points included pediatric UC activity index scores <10 points, defined as remission.

Results

At week 8, infliximab induced a response in 73.3% of patients (44 of 60) (95% confidence interval, 62.1%–84.5%; a positive result was defined by 95% confidence interval lower limit >40%). Among responders, twice as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of 22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the overall remission rate at week 54 would be 28.6%. Serious adverse events and infusion reactions occurred in similar proportions in the q8w and q12w groups. No deaths, malignancies, opportunistic infections, tuberculosis, or delayed hypersensitivity reactions were reported.

Conclusions

Infliximab was safe and effective, inducing a response at week 8 in 73.3% of pediatric patients with moderate to severely active UC who did not respond to conventional therapy. The overall remission rate at week 54 for all enrolled patients was 28.6%, assuming the more effective q8w remission rate.

Section snippets

Eligibility

Eligible patients were 6–17 years old, inclusive, with moderately to severely active UC (defined as having a baseline [ie, week 0] Mayo score12 of 6–12 points, including an endoscopy subscore ≥2). A UC diagnosis, confirmed by biopsy, must have been established ≥2 weeks before screening. Patients must have failed to respond to adequate treatment with or have experienced medical complications or adverse effects from 5-aminosalicylic acid (5-ASA); compounds, immunomodulators (6-mercaptopurine

Patient Disposition, Baseline Characteristics, and Prior Concomitant Medication Use

Twenty-three investigative sites participated in the United States and Canada (52 of 60 patients, 86.7%) and Belgium and the Netherlands (8 of 60 patients, 13.3%).

All patients were receiving baseline UC medications (Table 1). Among enrolled patients, 53.3% (32 of 60 patients) were female, 81.7% (49 of 60 patients) were white, median age was 14.5 years, median C-reactive protein level was 0.3 mg/dL, median disease duration was 1.4 years, and 76.7% (46 of 60 patients) had extensive disease. The

Discussion

Our study achieved the primary efficacy end point of clinical response at week 8. Infliximab induced clinical response in 73.3% of patients. The criterion for a positive study was met because the lower limit of the 95% CI for the proportion of patients in clinical response was 62.1%, which is greater than the protocol-specified limit of 40%.

Efficacy was also demonstrated by multiple other measures and end points. Infliximab induced Mayo and PUCAI clinical remission in at least one-third of

Acknowledgements

Editorial and writing support was provided by James P. Barrett, an employee of the Medical Affairs Publications Group, Janssen Biotech, Inc. Members of the T72 Study Group are listed in the Appendix.

References (20)

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Conflicts of interest The authors disclose the following: Jeffrey Hyams, Harland S. Winter, Subra Kugathasan, Stanley Cohen, James Markowitz, Johanna Escher, Gigi Veereman-Wauters, Wallace Crandall, Robert Baldassano, and Anne Griffiths received research funding in conjunction with the conduct of this study. Jeffrey Hyams, James Markowitz, and Anne Griffiths received research funding in conjunction with other studies sponsored by Janssen Research & Development, LLC. Jeffry Hyams, Harland S. Winter, Subra Kugathasan, James Markowitz, Wallace Crandall, Robert Baldassano, and Anne Griffiths served as Consultants to Janssen Research & Development, LLC. Marion Blank, Lakshmi Damaraju, Jewel Johanns, and Cynthia Guzzo are employees of Janssen Research & Development, LLC. Subra Kugathasan, James Markowitz, and Wallace Crandall received honoraria from Janssen Research & Development, LLC. Stanley Cohen received other research grants from and chaired conferences sponsored by Janssen Research & Development, LLC.

Funding Janssen Research & Development, LLC, provided support for this study.

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