Achievement of a State of Inactive Disease at Least Once in the First 5 Years Predicts Better Outcome of Patients with Polyarticular Juvenile Idiopathic Arthritis

ALESSANDRA MAGNANI; ANGELA PISTORIO; SILVIA MAGNI-MANZONI; ALESSANDRA FALCONE; GIUSEPPINA LOMBARDINI; MARCIA BANDEIRA; FEDERICA ROSSI; ILARIA SALA; ALBERTO MARTINI; ANGELO RAVELLI

doi:10.3899/jrheum.080560

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Figure 1.
Median values (first and third quartiles) of the restricted joint count at last followup visit in patients who did not achieve (No ID), achieved only once (1 ID), or achieved 2 or more times (≥ 2 ID) the state of inactive disease in the first 5 years after first observation.
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Figure 2.
Median values (first and third quartiles) of the Juvenile Arthritis Damage Index (JADI)-Articular at last followup visit in patients who did not achieve (No ID), achieved only once (1 ID), or achieved 2 or more times (≥ 2 ID) the state of inactive disease in the first 5 years after first observation.
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Figure 3.
Median values (first and third quartiles) of the Childhood Health Assessment Questionnaire (CHAQ) disability index at last followup visit in patients who did not achieve (No ID), achieved only once (1 ID), or achieved 2 or more times (≥ 2 ID) the state of inactive disease in the first 5 years after first observation.
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Figure 4.
Median values (first and third quartiles) of the Poznanski score of radiographic damage at last followup visit in patients who did not achieve (No ID), achieved only once (1 ID), or achieved 2 or more times (≥ 2 ID) the state of inactive disease in the first 5 years after first observation.

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Table 1.

Comparison of baseline clinical features between patients included and not included in the study. Values are medians (first and third quartiles) unless otherwise indicated.

Feature	n	Patients Included, n = 123	n	Patients Not Included, n = 114	p
No. (%) male/female	123	32 (26)/91 (74)	114	37 (32.5)/77 (67.5)	0.28^a
ILAR category, n (%)^†	123		114		0.15^a
Extended oligoarthritis		56 (45.5)		45 (39.5)
Polyarthritis, 5 rheumatoid factor-positive		32 (26)		43 (37.7)
Systemic arthritis		35 (28.5)		26 (22.8)
Age at disease onset, yrs	123	3.9 (2; 6.6)	114	3.4 (2; 6.5)	0.58^b
Disease duration, yrs	123	0.6 (0.2; 1.8)	114	0.5 (0.2; 1.3)	0.11^b
Physician’s global assessment^*	78	7.5 (5.3; 9.0)	75	8.4 (7.3; 10)	0.008^b
Parent’s global assessment^*	63	3.3 (1.6; 5.5)	58	3.9 (1.2; 6.0)	0.55^b
Parent’s pain assessment^*	49	3.4 (2.0; 6.0)	40	3.4 (1.2; 5.5)	0.72^b
Swollen joint count	118	4.0 (2.0: 9.0)	102	5.0 (3.0; 9.0)	0.57^b
Tender joint count	118	3.5 (1.0; 8.0)	102	5.0 (2.0; 9.0)	0.09^b
Restricted joint count	118	4.0 (1.0; 8.0)	102	5.0 (2.0; 8.0)	0.21^b
Active joint count	118	5.0 (3.0; 12.0)	102	6.0 (3.0; 11.0)	0.38^b
CHAQ disability index^**	86	0.6 (0.1; 1.0)	75	0.7 (0.4; 1.2)	0.10^b
ESR, mm/h; normal < 20 mm/h	118	45.0 (30.0; 75.0)	103	52.0 (32.0; 71.0)	0.45^b
C-reactive protein, mg/dl^††	74	2.6 (0.6; 6.5)	51	2.0 (0.6; 5)	0.53^b
Poznanski score, units^***	64	–0.8 (–1.5; 0.1)	43	–1 (–2; 0.3)	0.54^b

ILAR: International League of Associations of Rheumatology; CHAQ: Childhood Health Assessment Questionnaire; ESR: erythrocyte sedimentation rate.
↵† For purposes of the analysis, patients with ILAR categories of psoriatic arthritis (n = 6) and undifferentiated arthritis (n = 7) were classified within polyarthritis and extended oligoarthritis categories based on the number of joints affected in the first 6 months of disease.
↵a Chisquare test;
↵b Mann-Whitney U test.
↵* Range 0 (best) to 10 (worst);
↵** range 0 (best) to 3 (worst);
↵†† normal < 0.3 mg/dl;
↵*** abnormal score < –2 units.

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Table 2.

Baseline clinical features, followup duration, and antirheumatic medications among patients who achieved or did not achieve the state of inactive disease in the first 5 years after baseline. Values are medians (first and third quartiles) unless otherwise indicated.

	No Inactive Disease,		1 Episode of Inactive Disease,		≥ 2 Episodes of Inactive Disease,
Feature	n	n = 62	n	n = 40	n	n = 21	p
No. (%) male/female	62	18 (29)/44 (71)	40	9 (23)/31 (78)	21	5 (24)/16 (76)	0.74^a
ILAR category, n (%)	62		40		21		0.16^a
Oligoarthritis extended		23 (37.1)		23 (57.5)		10 (47.6)
Polyarthritis		17 (27.4)		11 (27.5)		4 (19)
Systemic arthritis		22 (35.5)		6 (15)		7 (33.3)
Age at disease onset, yrs	62	4.2 (2.1; 6.6)	40	3.3 (2; 6.4)	21	3.9 (1.9; 4.8)	0.67^c
Disease duration, yrs	62	0.8 (0.3; 1.8)	39	0.4 (0.2; 1.5)	21	0.6 (0.4; 1.9)	0.40^c
Interval disease onset–first observation, yrs	62	0.8 (0.4; 1.8)	40	0.5 (0.2; 1.5)	21	0.6 (0.4; 1.9)	0.41^c
Interval first–last observation, yrs	62	8.1 (6.8–10.5)	40	7.0 (6.5–9.0)	21	6.7 (6.4–7.4)	0.06^c
Interval disease onset–methotrexate start, yrs	62	2.1 (0.8; 4.2)	40	2.1 (0.8; 4.8)	21	1.3 (0.6; 3.0)	0.25^c
Physician’s global assessment	32	7.5 (7.5; 10)	27	7.3 (4.6; 8.1)	19	7.5 (6.1; 9.0)	0.09^c
Parent’s global assessment	22	3.0 (2.0; 6.9)	23	3.3 (1.5; 6.3)	18	4 (1.7; 5.5)	0.83^c
Parent’s pain assessment	13	5.0 (0.7; 6.0)	21	3.4 (2.3; 6.5)	15	3.3 (2.0; 5.0)	0.97^c
Swollen joint count	59	4.0 (2.0; 10.0)	38	3.0 (2.0; 5.0)	21	7.0 (4.0; 17.0)	0.009^*^c
Tender joint count	59	3.0 (0.0; 9.0)	38	2.5 (1.0; 5.0)	21	6.0 (3.0; 16.0)	0.02^†^c
Restricted joint count	59	4.0 (1.0; 9.0)	38	3.5 (1.0; 6.0)	21	6.0 (3.0; 8.0)	0.17^c
Active joint count	59	5.0 (3.0; 14.0)	38	4.0 (2.0; 7.0)	21	7.0 (5.0; 22.0)	0.02^††^c
CHAQ disability index	39	0.6 (0.0; 1.0)	28	0.5 (0.2; 1.1)	19	0.8 (0; 1.3)	0.59^c
Erythrocyte sedimentation rate, mm/h	59	50 (32; 77)	38	43.5 (25; 67)	21	37 (22; 56)	0.27^c
C-reactive protein, mg/dl	29	4.6 (0.6; 6.5)	26	1.6 (0.7; 6.8)	19	1.9 (0.4; 5.2)	0.44^c
Poznanski score, units	33	–0.86 (–1.6; –0.1)	18	–0.8 (–1; 0.1)	13	–0.5 (–1.3; 0.1)	0.75^c
Duration of methotrexate therapy, yrs^**	62	4.4 (3.6; 5.0)	40	3.8 (3.1; 4.6)	21	3.9 (3.2; 4.7)	0.04^***^c
No. (%) patients who received cyclosporine^**	62	31 (50.0)	40	11 (27.5)	21	3 (14.3)	0.005^†††^a
No. (%) patients who received sulfasalazine^**	62	11 (17.7)	40	7 (17.5)	21	0 (0.0)	0.09^b
No. (%) patients who received etanercept^**	62	11 (17.7)	40	7 (17.5)	21	1 (4.8)	0.37^b
No. (%) patients who received prednisone^**	62	21 (33.9)	40	9 (22.5)	21	5 (23.8)	0.40^a

ILAR: International League of Associations of Rheumatology; CHAQ: Childhood Health Assessment Questionnaire. See Table 1 for score ranges of outcome measures.
↵** In the first 5 years after first observation.
↵a chi-squared test;
↵b Fisher’s exact test;
↵c Kruskal-Wallis test. Post-hoc comparisons:
↵* swollen joint count is greater in patients with ≥ 2 episodes of inactive disease than in patients with 1 episode of inactive disease (Dunn’s test; p < 0.01);
↵† tender joint count is greater in patients with ≥ 2 episodes of inactive disease than in patients with 1 episode of inactive disease (Dunn’s test; p < 0.05);
↵†† active joint count is greater in patients with ≥ 2 episodes of inactive disease than in patients with 1 episode of inactive disease (Dunn’s test; p < 0.05);
↵*** Dunn’s test not significant;
↵††† frequency of cyclosporine therapy is greater in patients with no inactive disease than in patients with ≥ 2 episodes of inactive disease (chi-square with Bonferroni correction; p = 0.01).

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Table 3.

Best-fitting models of logistic regression analysis.

	Outcome
	No Inactive Disease (n = 50/92; 54.3%) OR (95% CI)	≥2 Episodes of Inactive Disease (n = 14/88; 15.9%) OR (95% CI)
Cyclosporine therapy (yes/no)	3.97 (1.57–10.06)^**	0.13 (0.03–0.65)^**
Duration of methotrexate therapy (>4/≤ 4 yrs)	2.67 (1.08–6.62)^*
Swollen joint count at baseline (> 4/≤ 4)		5.99 (1.45–24.77)^**
Area under ROC curve of the model	0.72	0.77