Juvenile arthritis damage index predicts poor response to biological treatment: A prospective cohort study

Table 1 The predictors of damage in patients with juvenile idiopathic arthritis

Parameter	Se	Sp	OR (95%CI)	RR (95%CI)	P value
Polyarthricular JIA category	35.0	86.5	3.5 (1.3-9.0)	1.6 (1.2-2.2)	0.017
ANA positivity	45.0	75.0	2.5 (1.1-5.5)	1.5 (1.1-2.1)	0.027
Arthritis of ≥ 5 joints at onset	25.0	90.4	3.1 (1.1-9.3)	1.5 (1.1-2.1)	0.034
Active joints > 8 at the study inclusion	55.0	76.9	4.1 (1.8-9.3)	1.8 (1.3-2.6)	< 0.001
Parental/patient VAS > 6 cm	53.3	71.2	2.8 (1.3-6.2)	3.2 (1.6-6.2)	0.009
MDVAS > 6 cm	88.3	50.0	7.6 (2.9-19.7)	3.2 (1.6-6.2)	< 0.001
JADAS71 > 17.7 points	81.7	48.1	4.1 (1.8-9.7)	2.1 (1.3-3.6)	0.001
CHAQ > 0 points	68.3	59.6	3.2 (1.5-6.9)	1.7 (1.2-2.6)	0.003
Ankylosis, confirmed by X-ray	29.8	97.9	19.5 (2.4-155.8)	2.2 (1.7-3.0)	0.008
MRI-confirmed erosions	49.0	90.9	12.5 (3.8-40.9)	2.2 (1.6-3.1)	< 0.001

Se: Sensitivity; Sp: Specificity; CI: Confidence interval; OR: Odds ratio; RR: Relative risk; JIA: Juvenile idiopathic arthritis; ANA: Antinuclear antibody; VAS: Visual-analogue scale; MDVAS: Physician’s visual-analogue scale; JADAS: Juvenile arthritis disease activity score; CHAQ: Childhood Health Assessment Questionnaire; MRI: Magnetic resonance imaging.

Table 2 The final predictors of damage development (multiple regression analysis data)

Predictor	Β	SE	P value
Intercept	0.108	0.084	0.200
Active joints > 8 at the study inclusion	0.191	0.093	0.044
MDVAS > 6 cm	0.318	0.102	0.003
MRI-confirmed erosions	0.355	0.097	< 0.001

MDVAS: Physician’s visual-analog scale; MRI: Magnetic resonance imaging.

Table 3 Baseline comparison of the studied population, with and without damage, n (%)

Parameter	JADI (+ ve), n = 60	JADI (- ve), n = 52	P value
Age at study inclusion, years, IQR	11.6 (7.5-15.4)	13.1 (9-16.1)	0.244
Sex, females	36 (60.0)	29 (55.7)	0.651
JIA category, according to the ILAR[3]
Oligoarthritis	23 (38.0)	19 (36.5)	0.845
Polyarthritis	21 (35.0)	7 (13.5)	0.017
Psoriatic arthritis	4 (7.0)	4 (8.0)	0.834
Enthesitis-related arthritis	12 (20.0)	22 (42.0)	0.019
JIA onset age, years, IQR	8.7 (3-12)	10.1 (6.9-13.1)	0.079
Diagnosis delay, moths, IQR	3.9 (1-12)	4 (1.5-10)	0.560
JIA duration, years, IQR	2.3 (0.8-4.5)	1.6 (0.9-3.2)	0.360
Time before non-biologic DMARDs, months, IQR	5 (2-14)	6 (2.2-23)	0.491
ANA positivity (> 1:320)	27 (45.0)	13 (25.0)	0.027
RF-positivity	6 (10.0)	2 (3.8)	0.207
ACCP-positivity	6 (10.0)	1 (1.9)	0.078
Enthesitis	6 (10.0)	14 (26.9)	0.019
Uveitis	6 (10.0)	4 (7.7)	0.669
Arthritis of ≥ 5 joints at onset	15 (25.0)	5 (9.6)	0.034
Number of past nbDMARDs
No	3 (5.0)	5 (9.6)	0.345
One	47 (78.3)	37 (71.2)	0.512
Two	10 (16.7)	9 (17.3)	0.872
Three	0 (0)	1 (1.9)	0.943
No episodes of nbDMARDs therapy interruption	45 (75.0)	41 (78.8)	0.631
Past corticosteroid treatment	11 (18.3)	6 (11.5)	0.314
Past corticosteroid treatment duration	-	-	0.622
< 3 months	8 (13.3)	5 (9.6)	-
≥ 3 months	3 (5.0)	1 (1.9)	-
Corticosteroid treatment duration, IQR	1 (0.3-6)	1.8 (0.2-2.6)	0.802
Remission duration ≥ 6 months in the past	5 (8.3)	5 (9.6)	0.812
Active joints, IQR	9 (6-17.5)	6 (4-8)	< 0.001
Swollen joints, IQR	8 (6-15)	5 (3-7.5)	< 0.001
Painful joints, IQR	8 (5.5-15)	6 (3.5-8)	0.001
Joints with limited ROM, IQR	3 (2-4.5)	2 (1.5-2)	< 0.001
Parental/patient VAS (cm), IQR	7 (5-7)	2 (1.5-2)	0.045
MDVAS (cm), IQR	7 (7-8)	6 (4-8)	< 0.001
ESR (mm/hour), IQR	10 (5-24)	11 (5.5-19)	0.896
С-reactive protein (mg/L), IQR	1.8 (0.3-10.5)	1.5 (0.2-5.6)	0.512
JADAS71, IQR	23.5 (20-34.2)	19.1 (15-25)	< 0.001
CHAQ, IQR	0.4 (0-0.8)	0 (0-0.3)	0.003
X-ray changes	47/60 (78.3)	32/52 (61.5)	-
Early signs	25/47 (53.2)	29/47 (90.6)	0.002
Erosions	8/47 (17.0)	2/47 (6.3)	0.286
Ankylosis	14/47 (29.8)	1/47 (3.1)	0.008
MRI-changes	51/60 (85.0)	44/52 (84,6)	< 0.001
Bone marrow edema	26/51 (51.0)	40/44 (90.9)	-
Erosions	25/51 (49.0)	4/44 (9.1)	-

+ ve: Positive; - ve: Negative; JADI: Juvenile arthritis damage index; JIA: Juvenile idiopathic arthritis; DMARDs - Disease-modified antirheumatic drugs; ILAR: International League of Associations of Rheumatology; ANA: Antinuclear antibody; RF: Rheumatoid factor; ACCP: Anti-cyclic citrullinated peptide; nbDMARDs: Non-biologic disease-modified antirheumatic drugs; ROM: Range of the motion; VAS: Visual-analogue scale; MDVAS: Physician’s visual-analogue scale; ESR: Erythrocyte sedimentation rate; JADAS: Juvenile arthritis disease activity score; CHAQ: Childhood Health Assessment Questionnaire; MRI: Magnetic resonance imaging; IQR: Interquartile range.

Table 4 Comparative analysis of clinical parameters of patients whose juvenile arthritis damage index improved vs remained unchanged/deteriorated on biological disease-modified antirheumatic drugs therapy (end of study), n (%)

Parameter	Improved JADI, n = 41	Non-improved JADI, n = 19	P value
Presence of the JADI–A at the baseline	38 (92.7)	14 (73.7)	0.044
Baseline JADI-A, IQR	2 (1-5)	1 (0-2)	0.014
Patients with uveitis	2 (4.9)	4 (21.1)	0.05
Treatment with nbDMARDs at the EOS	40 (97.6)	14 (73.7)	0.004
Stable nbDMARD treatment during the study	39 (95.1)	12 (63.2)	0.001
Stable bDMARD treatment during the study	36 (87.8)	12 (63.2)	0.03
Bone osteonecrosis (JADI-E)	3 (7.3)	6 (31.6)	0.014
Eye damage (JADI-E)	0 (0)	2 (10.5)	0.034
MRI-confirmed bone erosions, n/n performed (%)	14/37 (37.8)	11/15 (73.3)	0.021
bDMARD treatment:			0.297
Etanercept	19 (46.3)	8 (42.1)
Golimumab	2 (4.9)	3 (15.8)
Adalimumab	14 (34.1)	8 (42.1)
Tofacitinib	4 (9.8)	0 (0)
Secukinumab	2 (4.9)	0 (0)

JADI-A: Juvenile arthritis damage index - articular damage; nbDMARDs: Non-biologic disease-modified antirheumatic drugs; EOS: End of study; bDMARD: Biologic disease-modified antirheumatic drugs; JADI-E: Juvenile arthritis damage index - extraarticular damage; MRI: Magnetic resonance imaging; IQR: Interquartile range.

Table 5 Comparative analysis of clinical parameters of patients whose JADI-A improved vs remained unchanged/deteriorated on biologic disease-modified antirheumatic drugs therapy (end of study), n (%)

Parameter	Improved JADI-A, n = 38	Non-improved JADI-A, n = 14	P value
Baseline JADI-A, IQR	2 (1-6)	1.5 (1-2)	0.096
Patients with uveitis	2 (5.3)	2 (14.3)	0.278
Treatment with nbDMARDs at the EOS	38 (100)	9 (64.3)	0.001
Stable nbDMARD treatment during the study	37 (97.4)	8 (57.1)	0.001
Stable bDMARD treatment during the study	33 (86.8)	9 (64.3)	0.067
Bone osteonecrosis (JADI-E)	2 (5.3)	3 (21.4)	0.079
MRI-confirmed bone erosions	13/35 (37.1)	8/12 (66.7)	0.075
bDMARD treatment			0.249
Etanercept	17 (44.7)	5 (35.7)
Golimumab	2 (5.3)	3 (21.4)
Adalimumab	13 (34.2)	6 (42.8)
Tofacitinib	4 (10.5)	0 (0)
Secukinumab	2 (5.3)	0 (0)

JADI-A: Juvenile arthritis damage index - articular damage; nbDMARDs: Non-biologic disease-modified antirheumatic drugs; EOS: End of study; bDMARD: Biologic disease-modified antirheumatic drugs; JADI-E: Juvenile arthritis damage index - extraarticular damage; MRI: Magnetic resonance imaging; IQR: Interquartile range.

Table 6 Predictors of articular damage improvement (multiple regression analysis data), n (%)

Predictor	Β	SE	P value
Intercept	-0.026	0.198	0.896
Treatment with nbDMARDs at the EOS	0.343	0.119	0.006
Stable bDMARD treatment during the study	0.249	0.119	0.042

EOS: End of study; bDMARD: Biologic disease-modified antirheumatic drugs; nbDMARDs: Non-biologic disease-modified antirheumatic drugs.