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P367. Rate of and response to dose escalation in paediatric patients with Crohn's disease from IMAgINE 1

M. Dubinsky1, J. Rosh2, W.A. Faubion3, J. Kierkus4, F. Ruemmele5, J. Hyams6, S. Eichner7, Y. Li7, A. Lazar8, R.B. Thakkar7, 1Cedars-Sinai Medical Center, Pediatric Inflammatory Bowel Disease Program, Los Angeles, United States, 2Goryeb Children's Hospital/Atlantic Health, Pediatric Gastroenterology, Morristown, United States, 3Mayo Clinic, Gastroenterology, Rochester, United States, 4The Children's Memorial Health Institute, Gastroenterology, Hepatology and Feeding Disorders, Warsaw, Poland, 5Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, APHP, Paris, France, 6Connecticut Children's Medical Center, Division of Digestive Diseases, Hartford, United States, 7AbbVie Inc, GPRD, North Chicago, United States, 8AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany

Background

Patients (pts) enrolled in the adalimumab (ADA) paediatric Crohn's disease (CD) clinical trial IMAgINE 1 not responding to every other week (eow) dosing could escalate to weekly dosing [1]. Week (wk) 52 clinical outcomes are examined in pts who moved to weekly dosing in IMAgINE 1.

Methods

In IMAgINE 1, pts aged 6–17, with a baseline (BL) PCDAI score >30 and CD resistant or intolerant to conventional therapy, received open-label induction of ADA at wks 0/2 according to body weight (≥40 kg, 160/80 mg; <40 kg, 80/40 mg). At wk 4, pts were randomised to receive higher dose [HD] (≥40 kg, 40 mg every other wk (eow); <40 kg, 20 mg eow) or lower dose [LD] (≥40 kg, 20 mg eow; <40 kg, 10 mg eow) ADA maintenance therapy. Pts experiencing disease flare or non-response could move to blinded weekly dosing after wk 12, then to open-label weekly HD dose ADA for continued flare/non-response. Remission (PCDAI ≤10) and response (PCDAI decrease ≥15 points from BL) were assessed at wk 52 for pts who moved to weekly dosing. Subgroup analyses were performed by prior infliximab use (IFX) and by disease severity based on the median of BL PCDAI observed in the study population (moderate CD, PCDAI <40; severe CD, PCDAI ≥40). Non-responder imputation was used for missing data. Adverse event (AE) rates were assessed per 100 patient-years (PY) for pts on eow dosing and those who dose escalated.

Results

Of the 188 randomised pts, 83 (44.1%) moved to weekly dosing. More pts receiving LD ADA or pts with severe CD dose escalated than pts receiving HD ADA or pts with moderate CD, but the differences were not statistically significant (50.5% vs 37.6%, p = 0.08 LD vs HD ADA; 47.2% vs 40.0%, p = 0.33, severe vs moderate CD). Of the 83 pts who dose escalated, 39 (47.0%) received prior IFX. Of the 105 pts that remained on eow dosing, 44 (41.9%) received prior IFX. Remission and response rates at wk 52 for pts who moved to weekly dosing are shown in the table. The exposure-adjusted rates of serious AEs and serious infections were similar between pts who dose escalated and those who remained on eow dosing.

Table: Week 52 remission and response rates in pts who dose escalated
LD ADA (20/10 mg), N = 48HD ADA (40/20 mg), N = 35All ADA, N = 83
Remission, n (%)9 (18.8)11 (31.4)20 (24.1)
Response, n (%)23 (47.9)20 (57.1)43 (51.8)

Conclusion

Remission and response were achieved by one-fourth and one half of the pts who dose escalated, respectively, suggesting weekly ADA dosing may be a beneficial treatment strategy for paediatric pts with CD who failed to achieve a desired response or experienced a disease flare on eow dosing. No increased safety risks were observed with weekly dosing.

1. Hyams J, et al. Gastroenterol. 202; 143: 365.