Description of clinical and demographic data at baseline
One hundred twenty-five patients were enrolled in this study; 100 patients with an established disease and 25 patients considered naïve.
The patients have a median age of 6.2 and 4.2 years at onset in the naïve and established cohort respectively, with a predominance of female (64% and 57% respectively). The distribution of age at onset follows a bimodal distribution, with a first peak between 1 and 4 years and a second peak between 9 and 12 years (Fig. 2).
The symptoms duration before diagnosis is respectively 10.8 and 7.3 months in the naïve and established cohort. A diagnosis delay of ≥ 12 months is associated to older age at onset and negativity of ANA. The mean body-mass index (BMI) is around the 75th percentile adjusted for sex and age for both cohorts (Table 1). All forms of JIA are represented in both cohorts, without significant differences between cohorts (Fig. 3).
Description of treatment among patients at baseline and during follow-up
In the established cohort, 98% of patients are or have been treated with methotrexate (MTX), while half had been treated with a bDMARD (most of which are still ongoing). Unsurprisingly, the patients most treated with bDMARDs have systemic arthritis, followed by extended form of oligoarthritis, enthesitis-related arthritis, RF-positive and –negative polyarthritis, and persistent form of oligoarthritis, among which respectively 77%, 76%, 73%, 50% and 40% of patients had been treated with bDMARDs.
Among the 25 naïve patients, MTX was started in 44% of patients during the 2 years of follow-up, and 2 children had started a bDMARD.
The details of these treatments are available in Supplementary material.
Approximately one-third of patients (36.8%) reported side effects during follow-up, mainly digestive intolerance (75%), followed by fatigue (11%), headache (7%), allergy at the injection site (4%) and irritability (3%).
Description of markers of auto-immunity and their relation with clinical characteristics
Positivity of ANA is found in 40% of naïve patients and 47% of established patients. Interestingly, 19% of patients developed uveitis (all appearing in oligoarthritis forms) and the occurrence of uveitis is strongly associated with the presence of ANA, underlined by an odds ratio of 6 (Table 2). Patients with uveitis are found to be significantly younger at disease onset and diagnosis with a median age of 1.8 and 1.9 years respectively, compared to 7.6 and 9.1 years respectively in unaffected patients (Table 2). In our cohort, they were also mostly female (71%).
HLA-B27 testing was performed on only 35 patients in our cohort. Among these patients, 25% of naïve patients and 37% of established patients are positive for HLA-B27.
Description of patients’ outcome during the 18 months of follow-up
Preliminary results from the analysis of the follow-up data show that within the naïve cohort (Fig. 4A), tender joint counts (TJC), C-reactive protein (CRP) and DAS28-CRP are significantly improved at 6 months, while TJC and physician visual analogue scale (VAS) are significantly improved at 12 months of follow-up. Furthermore, out of the 100 established patients (Fig. 4B), 54 had an active disease at baseline. Among them, TJC, swollen joint counts (SJC), physician VAS and DAS28-CRP are significantly improved at 6 months, while TJC, physician VAS and patient/parent VAS are significantly improved at 12 months. In total, 60 to 70% of patients responded to treatment at 6 months (regarding pediACR30), and persisted as long as 18 months. More detailed results are available in Supplementary material.
According to the most stringent definition of remission based on the ACR criteria, the naïve patients are, as expected, significantly more in remission at 12 months and 18 months than at baseline, reaching up to 55% of remission rate at 12 months and 75% at 18 months (Fig. 4C). Of those, 83% are still on medication at 12 months while 17% manage to reach remission off medication, rising to 33% at 18 months. The remission rates are stable among the whole established cohort during the 18 months of follow-up, but are interestingly different when comparing the ACR criteria and DAS28-CRP, while JADAS10 did not differ from the ACR criteria (Fig. 4D).
Globally, higher remission rates are seen in systemic arthritis, RF-negative polyarthritis and persistent forms of oligoarthritis (Fig. 4E-F).
Determination of clinical and biological markers of prognosis
The follow-up of naïve patients allows identifying female sex as a predictive marker of response to treatment at 12 months (Table 6). The responders also tend to be older at onset and negative for ANA. The details of these analyses are available in Supplementary material.
No predictive markers of inactivity at 6 months or remission on and off treatment at 12 months could be identified during follow-up.
Impact on the daily life
The financial burden for the parents is on average 91€ per month. It includes costs related to physiotherapy, accessories, travel expenses, and medication. Among the 47 patients who completed the specific questionnaires during the follow-up, 5 children benefit from a home care nurse’s visit. Approximately 40% of the children have regular physiotherapy. Around 80% of patients manage to attend gymnastics classes, of which 10% need an adaptation during sports practice. Two thirds of the patients also practice an extracurricular sport.