Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease

Figures & data

Table 1. Background data of the patients with pediatric-onset inflammatory bowel disease and treated with anti-TNF-alpha antagonist adalimumab between 2012 and 2018 at two tertiary care hospitals in Finland.

No. of patients	n = 75
Male (%)	43 (57%)
Age at diagnosis, years
median (interquartile range)	11.2 (8.4–13.6)
Diagnosis
Crohn	57 (76%)
L1
L2
L3
Ulcerative colitis	10 (13.3%)
E2
E3
E4
Unclassified	8 (10.7%)
Disease duration at induction of adalimumab < 1 year	21 (28%)
Anti-TNFα naïve	15 (20%)
Immunosuppressive medication at induction of adalimumab n (%)	33 (44%)
Azathioprine	13 (17%)
Methotrexate	17 (23%)
Azathioprine and methotrexate	3 (4%)
Therapy with glucocorticoids at induction	40 (53%)
Perianal disease	7 (9.3%)
Surgery	7 (9.3%)
Growth impairment	12 (16%)
Pubertal delay	8 (10.7%)

Disease extent is presented according to Paris classification [34].

Table 2. Therapy with anti-TNF-alpha antagonist adalimumab (ADA) of the patients with pediatric-onset inflammatory bowel disease.

No. of patients	n = 75
ADA induction
median, (interquartile range)	0.8 mg/kg (0.67–1.1)
ADA maintenance dose after induction	40 mg biweekly*
ADA available at 1 year	46 (61%)
Duration of ADA therapy
median, years (interquartile range)	1.5 (0.58–2.46)
ADA ongoing at last follow up	39 (52%)
ADA discontinued during follow up	36 (48%)
Loss of response	23 (31%)
Adverse event	6 (8.0%)
Drug antibodies	4 (5.3%)
Other	3 (4.0%)
ADA levels at first measurement median, (interquartile range)	7.65 mg/L (5.33–9.95)
ADA levels during first 3 months	52 (69%)
	32 with levels > 7.5 mg/L
	20 with levels < 7.5 mg/L
ADA levels at 1 year	8.85 mg/L (5.32–11.25)**
ADA levels at last follow up median, (interquartile range)	8.8 mg/L (5.34-12.5)

*One 9-year-old received 25 mg; **Available in 30/46 (65%) on maintenance at 1 year (±8 weeks).

Figure 1. Trough levels during the first 3 months of adalimumab therapy are related to the probability of ongoing therapy during the first year.

Table 3. Disease activity at induction and last follow-up of ongoing adalimumab therapy.

	Induction	At 1 year	At latest follow up (a median of 1.5 years)
Fecal calprotectin μg/g
median (interquartile range)	765 (343–1800)	295 (118–636)	438 (166–976)*
Fecal calprotectin categories**
<100 μg/g (remission)***	8.5% (6/71)	24% (8/34)	18% (12/66)
>1000 μg/g (exceedingly high)	35% (25/71)	12% (4/34)	23% (15/66)
CRP mg/L
Above cut-off < 3 mg/L***	48% (29/60)	21% (8/39)	38% (26/69)
PGA
Remission/mild disease activity	40% (29/72)	70% (28/40)	38% (28/74)
Steroid free	47% (35/75)	89% (40/45)	77% (57/74)
Combination therapy with immunosuppressants	44% (33/75)	20% (9/46)	26% (19/74)

*p < .05.

**[18].

***Cut-off for a raised value used by our hospital laboratories.

PGA: physicians’ global assessment, scale 1–3 [21].

Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011;17(6):1314–1321.

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Kolho KL, Raivio T, Lindahl H, et al. Fecal calprotectin remains high during glucocorticoid therapy in children with inflammatory bowel disease. Scand J Gastroenterol. 2006;41(6):720–725.

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Haapamäki J, Roine RP, Sintonen H, et al. Health-related quality of life in paediatric patients with inflammatory bowel disease related to disease activity. J Paediatr Child Health. 2011;47(11):832–837.

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