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P426. Long-term safety of adalimumab in paediatric patients with Crohn's disease

J. Rosh1, F. Ruemmele2, M. Dubinsky3, J. Escher4, J. Kierkus5, J. Hyams6, A. Lazar7, S. Eichner8, Y. Li8, R.B. Thakkar8, 1Goryeb Children's Hospital/Atlantic Health, Pediatric Gastroenterology, Morristown, United States, 2Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, APHP, Paris, France, 3Cedars-Sinai Medical Center, Pediatric Inflammatory Bowel Disease Program, Los Angeles, United States, 4Erasmus MC-Sophia Children's Hospital, Pediatric Gastroenterology, Rotterdam, Netherlands, 5The Children's Memorial Health Institute, Gastroenterology, Hepatology and Feeding Disorders, Warsaw, Poland, 6Connecticut Children's Medical Center, Division of Digestive Diseases, Hartford, United States, 7AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany, 8AbbVie Inc, GPRD, North Chicago, United States

Background

The safety profile of adalimumab (ADA) in children enrolled in the IMAgINE 1 [1] clinical trial and the open-label extension (OLE) has been reported up to 3 years [2]. A safety update, with up to 5 years of ADA exposure, is presented.

Methods

Patients (pts) completing the IMAgINE 1 trial could enroll in the OLE. Adverse events (AEs) were reported from the first dose through the June 30, 2013 cut-off or up to 70 days after the last ADA dose for any pt that received at least one dose of ADA. Rates of AEs were assessed per 100 patient-years (PY). Subgroup analysis by prior infliximab (IFX) use was performed.

Results

A total of 192 children have received at least one dose of ADA in IMAgINE 1 and the OLE, totaling 422.2 PY of exposure. As of June 30, 2013, 115/192 pts (59.9%), 82/192 (42.7%), 75/192 (39.1%), 58/192 (30.2%), and 15/192 (7.8%) have at least 1, 2, 3, 4, or 5 years of ADA exposure, respectively. An overview of the treatment-emergent AEs for all pts and by prior IFX use is shown in the table. The most common serious AE (SAE) was flare or worsening of CD and most (7/11) opportunistic infections were non-serious oral candidiasis. The exposure-adjusted rate of SAEs and AEs leading to discontinuation were significantly higher for IFX experienced pts than IFX naïve pts (Table). The rate of serious infections observed between pts receiving ADA with or without concomitant immunosuppressant (IMM) and/or corticosteroid (CS) use at baseline were 3.5 E/100PY ADA monotherapy, 6.2 E/100PY ADA + IMM, 4.4 E/100PY ADA + CS, and 12.5 E/100PY ADA + IMM + CS (p = 0.09). No malignancies or deaths have been reported to date.

Table (abstract P426): Treatment-emergent AEs as of 30 June 2013
Any ADA
(N = 192, 422.2 PY)
IFX naive
(N = 107, 288.8 PY)
Prior IFX
(N = 85, 133.4 PY)
n (%)Events (E/100 PY)n (%)Events (E/100 PY)n (%)Events (E/100 PY)
Any AE189 (98.4)2714 (642.8)107 (100)1727 (598.0)82 (96.5)987 (739.9)*
Serious AE88 (45.8)150 (35.5)43 (40.2)81 (28.0)45 (52.9)69 (51.7)*
AE leading to discontinuation57 (29.7)71 (16.8)27 (25.2)33 (11.4)30 (35.3)38 (28.5)*
Opportunistic infection (excl. TB)8 (4.2)11 (2.6)3 (2.8)6 (2.1)5 (5.9)5 (3.7)
Serious infection22 (11.5)29 (6.9)13 (12.1)18 (6.2)9 (10.6)11 (8.2)
Injection site reaction42 (21.9)105 (24.9)25 (23.4)65 (22.5)17 (20.0)40 (30.0)
Hematologic AE30 (15.6)39 (9.2)15 (14.0)21 (7.3)15 (17.6)18 (13.5)
*p < 0.001 IFX naive vs prior IFX (Poisson regression).

Conclusion

No new safety risks have been identified with prolonged ADA treatment in children with Crohn's disease. The safety profile of ADA in children with Crohn's disease continues to be consistent with previously published reports [1,2].

1. Hyams JS, et al. Gastroenterol. 2012; 143: 365.

2. Baldassano R, et al. Abstract presented at 21st UEG Week 2013.