Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody

Table 1 Baseline characteristics n (%)

Characteristics	Value
Patients (n)	18
Female	13 (72)
Age at diagnosis in yr, median (range)	7.8 (2.9-15.3)
Age on ADA start in yr, median (range)	14.4 (5.3-19.1)
Age at diagnosis < 10 yr	12 (67)
Age at diagnosis 10-17 yr	6 (33)
Disease location according to Paris classification
L1 small intestine	2 (11)
L2 colon	12 (67)
L3 small intestine and colon	10 (55)
L4a upper gastrointestinal tract	9 (50)
P perianal disease	2 (11)
Granuloma	4 (22)
IBD-related medications at start of adalimumab
Corticosteroids	11 (61)
5-aminosalicylic acid	14 (78)
Immunomodulatory agents
Azathioprine/6-mercaptopurine	4 (22)
Methotrexate	5 (28)
Cyclosporin/tacrolimus	2 (11)
Biologics
Prior infliximab use	17 (94)
Number of children on IFX at start of ADA	14 (78)
Duration of prior infliximab use (mo), median (range)	1 (0.5-2)
Number of infliximab infusion, median (range)	11 (7-23)
Allergic reactions to IFX	1 (6)
Calcium/vitamin D supplements	11 (61)

ADA: Adalimumab; IFX: Infliximab; IBD: Inflammatory bowel disease.

Table 2 Anthropometry, inflammatory marker and puberty status at start of adalimumab

Anthropometric details1
Weight SDS	-0.5 ± 1.2
Height SDS	-0.7 ± 1.1
BMI SDS	-0.5 ± 1.3
Inflammation
PCDAI	52 ± 16
CRP (mg/dL)	1.6 ± 1.6
ESR (mm/h)	49 ± 20.1
Leucocytes (/nL)	10.3 ± 4.4
Albumin (g/dL)	3.7 ± 0.6
Tanner staging2
Tanner 1	4 (22)
Tanner 2	3 (17)
Tanner 3	2 (11)
Tanner 4	6 (33)
Tanner 5	3 (17)

¹Results are presented as mean ± SD;

²Results are presented as number (% of total). BMI: Body mass index; PCDAI: Paediatric Crohn’s disease activity index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; SDS: Standard deviation score.

Table 3 Effects of adalimumab on inflammatory marker, growth and bone health

	Pre adalimumab	Post adalimumab	P value
Inflammation
ΔPCDAI1	15 (-20-55)	-19 (-65-20)	< 0.001
Disease activity2
No disease	2 (11)	6 (33)	NS
Mild	5 (28)	4 (22)	NS
Moderate/severe	6 (61)	8 (45)	NS
Anthropometry1
ΔWeight SDS	-0.2 [1.8- (-2.7)]	0 [1.7-(-1.7)]	NS
ΔHeight SDS	-0.1 [0.7- (-2.5)]	0 [1.3-(-2.5)]	NS
ΔBMI SDS	-0.5 (2.5-2.3)	-0.1 [0.7-(-2)]	NS
Bone density
BMC	0.64 (0.45-0.89)	0.64 (0.46-0.88)	NS
BMD SDS	-1.5 [0-(-3.3)]	-1.8 [0.3-(-3.8)]	NS
BMD SDS < -22	4 (22)	3 (17)	NS
BMAD SDS1	-1.2 [-0.1-(-3.8)]	-1 [-0.2-(-2.8)]	NS
BMAD SDS < -22	3 (17)	3 (17)	NS
Calcium homeostasis1
Albumin corrected Calcium	2.34 (2.06-2.5)	2.29 (1.79-2.49)	NS
Phosphate	1.46 (0.8-1.98)	1.45 (1.22-1.76)	NS
PTH	34.4 (19-66)	41.6 (18-109)	NS
25-OHD	36.4 (10.5-107)	35.5 (7.5-122)	NS
1.25-OHD	65.5 (22-180)	30 (5-165)	NS
Bone markers
Bone alkaline Phosphatase	39 (13-90)	29 (15-57)	NS
Osteocalcin	55 (16-125)	43 (17-90)	NS
C-telopeptide	0.94 (0.2-1.9)	0.8 (0.2-1.1)	NS
Corticosteroids
Children on steroids2	11 (61)	9 (50)	NS
Cumulative dose1	962 (0-3640)	1277 (0-2800)	NS
Daily dose	3.8 (2.5-50)	12.5 (5-50)	NS
Calcium/vitamin D2	8 (44)	10 (55)	NS

¹Results are presented as median (range);

²Results are presented as number (% of total). BMI: Body mass index; PCDAI: Paediatric Crohn’s disease activity index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; SDS: Standard deviation score; NS: Not significant.

Table 4 Effects of adalimumab on anthropometry and bone health for paediatric Crohn’s disease activity index non-responder and responder

	PCDAI remission (n = 6)			PCDAI mild + moderate/severe (n = 12)
	Pre ADA	Post ADA	P value	Pre ADA	Post ADA	P value
Anthropometry1
Weight SDS	-0.2 [0.6-(-1.8)]	0.3 [1.7-(-1.5)]	NS	0.2 [1.7-(-4)]	-1.1 [0.5-(-3.5)]	NS
ΔWeight SDS	0.5 [1.8-(-0.7)]c	0.2 [0.9-(-0.4)]	NS	-0.9 [0.7-(-2.7)]c	-0.1 [1.7-(-1.7)]	NS
Height SDS	-0.2 [0-(-3.3)]	-0.1 [1.2-(-0.6)]	NS	-0.5 [0.8-(-2.3)]	-1.2 [0.8-(-4)]	NS
ΔHeight SDS	-0.1 [0-(-0.2)]	0.2 [1.4-(-0.5)]a	NS	-0.5 [0.9-(-2.5)]	-0.3 [0.3-(-2.7)]a	NS
BMI SDS	-0.4 [0.4-(-1.2)]	0.1 [2.7-(-0.8)]a	NS	-0.2 [2.5-(-2.6)]	-1 [0.1-(-3.6)]a	0.03
ΔBMI SDS	0.6 [2.5-(-0.7)]	0.3 [0.7-(-0.2)]a	NS	-0.2 [0.5-(-2)]	-1.1 [1.2-(-2.3)]a	NS
ΔPCDAI	-6 [45-(-20)]	-65 [-15-(-65)]a	0.02	20 [55-(-10)]	-14 [20-(-40)]a	0.001
Bone density
BMC	0.59 (0.5-0.9)	0.71 (0.6-0.9)	NS	0.66 (0.5-0.9)	0.65 (0.5-0.7)	NS
BMD SDS	-1.3 [0-(-2)]	-1.4 [0.3-(-2.7)]	NS	-1.8 [0.3-(-3.3)]	-2.3 [-1.3-(-3.8)]	0.02
BMAD SDS	-1.2 [-0.5-(-2.7)]	-1.2 [-0.6-(-2)]	NS	-1.5 [0.1-(-2.8)]	-1 [0.2-(-2.8)]	NS
Calcium homeostasis
PTH	22 (19-29)c	33 (23-77)	NS	34 (22-49)c	43 (22-72)	NS
25-OHD	54 (34-73)	44 (13-82)	NS	61 (10-107)	44 (22-60)	NS
1.25-OHD	81 (37-116)	55 (22-81)	NS	51 (22-180)	26 (5-73)	NS
Bone markers
BAP	31 (20-57)	38 (28-44)a	NS	46 (14-90)	21 (17-35)a	NS
Osteocalcin	55 (41-101)	84 (34-90)	NS	60 (16-125)	37 (17-87)	NS
C-telopeptide	0.7 (0.3-1.2)	1 (0.2-1.1)	NS	1 (0.5-1.9)	1.1 (0.5-1.1)	NS
Corticosteroids
Daily dose	5 (2.5-45)	5 (5-15)	NS	7.5 (2.5-10)	40 (10-50)	NS
Cumulative dose	262 (0-927)	638 (0-2800)	NS	1960 (0-3640)	1330 (0-2188)	NS

¹Results are presented as median (range).

^cP < 0.05 vs mild + moderate/severe pre-adalimumab;

^aP < 0.05 vs mild + moderate/severe post-adalimumab. BMC: Bone mineral content; BMD: Bone mineral density; SDS: Standard deviation score; BMAD: Bone mineral apparent density; PTH: Parathyroid hormone; 25-OHD: 25-hydroxycholecalciferol; 1,25-OHD: 1,25-dihydroxycholecalciferol; BAP: Bone alkaline phosphatase; ADA: Adalimumab.

Table 5 Other factors than paediatric Crohn’s disease activity index predicting growth, lumbar spine bone mineralisation and lumbar bone mineral apparent density after initiation of adalimumab

Factors	Coefficient	95%CI	P value
ΔHeight SDS
25-OHD	0.6	0-0.04	0.048
ΔBMD SDS
Weight SDS	0.8	0.09-0.6	0.02
BMI SDS	0.7	0.04-0.5	0.03
ΔBMAD SDS
PCDAI at start	-0.7	-0.02-(-0.002)	0.02

SDS: Standard deviation score; 25-OHD: 25-hydroxycholecalciferol; IFX: Infliximab; BMD: Bone mineralisation density; BMAD: Bone mineral apparent density; PCDAI: Paediatric Crohn’s disease activity index.