Patient demographics
Data from n = 112 JIA patients was collected in this registry; n = 75 (67%) were female (Table 1). The median age at symptom onset in the total group was 5.4 yrs (IQR 2.0-9.7) and the mean ± SD age at recruitment was 11.7 ± 4.4 yrs. The most common subtype of JIA was PO (n = 35, 31.3%), with median onset at age of 2.8 yrs (IQR 1.7-7.0) and predominantly occurring in females (n = 26/35, 74.3%). The least common subtype was psoriatic arthritis (PsA) JIA (n = 2, 1.8%). The frequencies and percentages for other subtypes were as follows: RF- polyarthritis (n = 32, 28.6%), EO (n = 23, 20.5%), enthesitis-related arthritis (ERA) (n = 12, 10.7%), systemic onset arthritis (n = 5, 4.5%), and RF + polyarthritis (n = 3, 2.7%). No patients had undifferentiated disease. There were n = 11 (9.8%) newly diagnosed JIA cases at enrolment, seven (63.6%) of whom were female. The most common diagnosis was PO (n = 5/11, 45.5%), followed by n = 3/11 (27.3%) with RF- polyarthritis, n = 2/11 (18.2%) with ERA and n = 1/11 (9.1%) with RF + polyarthritis. The median age at symptom onset and the median age at recruitment was 13.3 yrs (IQR 2.7–16.3) and 15.8 yrs (IQR 7.3–17.4) for incident cases, and 4.9 yrs (IQR 1.8–9.3) and 11.9 yrs (IQR 8.4–14.9) for prevalent cases.
Disease course
At the time of recruitment, the median active joint count was zero (IQR 0-0.8), the median physician global assessment (PGA) was zero (IQR 0-1.1) and the median patient global evaluation (PGE) was 0.5 (IQR 0-2.4) for all JIA patients (Table 2).
Among n = 101 patients with established disease, the median number of active joints was zero (IQR 0–0), with n = 80/101 (79.2%) achieving an active joint count of zero at enrolment, with median PGA of zero (IQR 0–1.0). In contrast, n = 11 incident patients had a median of one active joint count (IQR 0–2.0), with a higher median PGA of 1.2 (IQR 0-1.9).
Based on the aforementioned cJADAS cut-offs [24], n = 18 (16.1%) children had high disease activity at the time of recruitment, with n = 10 of them diagnosed with PO and one with EO. Six had RF- polyarthritis and one had RF + polyarthritis. Patients with EO had significantly longer (p = 0.016) disease duration [median 7.5 yrs (IQR 3.4–9.9)] than those with PO [median 3.9 yrs (IQR 1.2–6.4)].
The median CHAQ score (disability index) was 0.1 (IQR 0-0.6); most (n = 61/112, 54.5%) had no or only mild disability. The distribution of the CHAQ score was highly skewed (mean 0.37) [37]. When the analysis of CHAQ score was limited to those within subtypes, no significant differences were found.
The median age at onset among patients with functional oligoarthritis (n = 40, 35.7%) and patients with functional polyarthritis (n = 72, 64.3%) was 3.6 yrs (IQR 1.8–8.9) and 6.2 yrs (IQR 2-9.9), respectively. There was a significant difference in age at recruitment between functional oligoarthritis and polyarthritis categories of JIA (p = 0.04). There was no significant difference in age at diagnosis across the two categories (p = 0.25). The median time from symptom onset to diagnosis was 0.3 yrs (IQR 0.2–0.9) and there was no significant between-group difference (p = 0.571, Mann-Whitney U Test).
Complications and comorbidities
Complications were seen in n = 40/112 (35.7%) patients. Over the course of JIA, uveitis was documented in n = 21/94 (22.3%) patients and none of them were incident patients. The other n = 18 patients had not received ophthalmology screening until the time of recruitment [38]. Most of those with uveitis (n = 17/21, 81%) were antinuclear antibody (ANA) positive, with seven of those (41.2%) having EO, six (35.3%) having RF- polyarthritis and four (23.5%) having PO. Of the remainder who had uveitis but were ANA negative (n = 4/21, 19%), three (75%) had EO and one (25%) had RF- polyarthritis. Of those patients with uveitis in our cohort, one had a cataract removed surgically and one had previously developed glaucoma. Patients with systemic onset disease, ERA, PsA and RF + polyarthritis had no uveitis. In this registry, musculoskeletal complications occurred in n = 10/112 (8.9%) patients, with the majority (n = 8/10, 80%) in the functional polyarthritis category. Musculoskeletal complications in this registry included micrognathia in four, fixed flexion deformity in three, erosive disease in two, joint damage in one, a pars defect in one, and muscle wasting in one patient.
Among n = 79 JIA patients having ever used Methotrexate (MTX), liver function test derangement associated with MTX therapy occurred in n = 2/79 (2.5%) PO patients. MTX intolerance was present in n = 10/79 (12.7%) patients, with anticipatory nausea and anxiety as well as needle phobia included in this category. Subcutaneous atrophy, which resulted from intra-articular steroid injection, was present in n = 1/35 (2.9%) PO and n = 1/23 (4.3%) EO patient.
Macrophage activation syndrome (MAS) affected n = 1/5 (20%) of the systemic onset patients. Growth retardation occurred in n = 1/5 (20%) systemic JIA patients due to persistent disease activity and high-dose steroid exposure.
In this registry, n = 49/112 (43.8%) patients had at least one comorbidity and n = 34/49 (69.4%) of them were in the functional polyarthritis category. Common comorbidities for JIA in our cohort included anxiety and depression (n = 5, 4.5%), asthma (n = 5, 4.5%), diseases of the skin and subcutaneous tissue (including paronychia, eczema and psoriasis, n = 4, 3.6%), autism spectrum disorder (n = 4, 3.6%), iron deficiency/anaemia (n = 4, 3.6%), developmental delay (n = 4, 3.6%), eye disease (n = 3, 2.7%), IBD (n = 2, 1.8%), coeliac disease (n = 2, 1.8%), Type 1 Diabetes (n = 2, 1.8%), chondromalacia patellae (n = 2, 1.8%), Sinding-Larsen Syndrome (n = 2, 1.8%), Epilepsy (n = 2, 1.8%) and short stature (n = 2, 1.8%). Other comorbidities were also seen in very few patients, including but not limited to Lymphoedema (n = 1, 0.9%), Hypothyroidism (n = 1, 0.9%), congenital heart disease (n = 1, 0.9%), Cardio-facio-cutaneous Syndrome (n = 1, 0.9%), Sever's disease (n = 1, 0.9%), Kawasaki's disease (n = 1, 0.9%), and hypertrichosis (n = 1, 0.9%).
Medication
The exposure of the cohort to medications is detailed in Table 3. At enrolment, approximately n = 29/112 (25.9%) were no longer taking medication. Non-steroidal anti-inflammatory drugs (NSAIDs) had been used in most patients (n = 100/112, 89.3%), followed by non-biologic disease-modifying anti-rheumatic drugs (DMARDs) used in n = 83/112 (74.1%). Of these 83 patients, MTX had been used in n = 79/83 (95.2%) JIA patients. Sulfasalazine (n = 8/83, 9.6%) and Leflunomide (n = 6/83, 7.2%) had also been used in treating our patients.
Eighteen out of 23 (78.3%) patients with EO and n = 25/35 (71.4%) with PO had received intra-articular steroid therapy, compared to n = 10/54 (18.5%) in the other JIA subtypes combined. Use of oral steroids had been more common in systemic onset patients (n = 5/5, 100%) and patients with polyarthritis (n = 2/3, 66.7% in RF + polyarthritis and n = 19/32, 59.4% in RF- polyarthritis).
Biologics had been used in n = 26/112 (23.2%) patients, including Adalimumab (n = 20, 76.9%), Etanercept (n = 6, 23.1%), Tocilizumab (n = 2, 7.7%) and Anakinra (n = 1, 3.8%). At enrolment, n = 22/112 (19.6%) were using biologics. A relatively lower proportion (n = 1/35, 2.9%) of children with PO were using or had used biologics, reflecting their least aggressive disease activity.
Associations between disease activity and patient-reported data
There was a significant positive correlation between CHAQ score and cJADAS (Spearman R = 0.446, p < 0.001), and between patient/carer-reported pain visual analogue scale (VAS) and cJADAS (Spearman R = 0.700, p < 0.001), which indicates a consistency of patient- and clinician-assessed disease activity. A negative correlation was also found between disease duration and PGA (Spearman R=-0.206, p = 0.029).