Study design

This was an observational prospective feasibility study in participants who had received a new diagnosis of JIA, or those participants who had flaring disease requiring induction of remission.

Sites were asked to treat participants as per routine clinical care, with the CS route and doses chosen to be in keeping with their prior clinician decision.

Eligibility criteria

Children and adolescents aged < 16 years who had a new diagnosis of JIA or flaring disease requiring induction of remission that needed CS treatment were eligible for registration.

Participants who had arthritis as part of another disorder, such as connective tissue disease, or who had haemophagocytic lymphohistiocytosis or a severe infection complicating their JIA at the time of disease flare, were not eligible to take part in the study.

Ethics approval

The trial protocol was not initiated until it had received the favourable opinion of the main REC (16/NE/0047) on 21 September 2017. Subsequent to this, it was reviewed at the R&D offices at participating sites.

The trial and any subsequent amendments were reviewed and approved by North East – Newcastle & North Tyneside 3 REC (16/NE/0047).

Recruitment

The study was carried out in 15 UK centres. Participants were identified through paediatric rheumatology outpatient clinics.

Informed consent

This study recruited CYP aged < 16 years. Informed consent procedures reflected the legal and ethics requirements to obtain valid informed consent for this population. Prior written informed consent was required for all trial participants.

Information was provided to potential participants and their families verbally and in writing. All of the participants had the opportunity to discuss the project with the responsible investigator at the site and/or a designated member of the research team. Discussions were supported with detailed written and ethically approved patient information sheets and consent forms that were provided to CYP and their families.

All CYP and their families were given the opportunity to ask any questions that they had, to discuss the study with their surrogates and time to consider the information prior to agreeing to participate.

Registration

Participants were registered using a web-based system once all of the eligibility criteria had been confirmed.

Outcome measures

Data were collected at three time points during the course of the study: baseline, 6 weeks and 12 weeks.

The following outcomes were measured:

1.

JADAS.

This is composed of four components:

• physician global assessment of disease activity (measured on a 0–10 point scale)
• parent/patient global assessment of well-being (measured on a 0–10 point scale)
• active joint count in 71 joints
• ESR.

The cJADAS is composed of all of the above components but does not include the ESR or the CRP. The JADAS and cJADAS are calculated as a simple sum of scores from the components detailed above, which give global scores of 0–101 and 0–91 for the JADAS-71 and cJADAS-71, respectively.

2.

functional ability (CHAQ)

3.

Physician Global Assessment of Disease Activity

4.

number of active joints

5.

ACR Pedi JIA core set – ACR Pedi 30, ACR Pedi 50, ACR Pedi 70, ACR Pedi 90 and ACR Pedi 100 levels.

The JIA core set criteria assessed at each study visit are:

• physician global assessment of disease activity
• parent/patient assessment of overall well-being
• functional ability (CHAQ)
• number of joints with active arthritis
• number of joints with limited range of movement
• ESR.

The ACR Pedi 30, 50, 70, 90 and 100 levels are defined as 30%, 50%, 70%, 90% and 100% improvement, respectively, in a minimum of three variables in the core set with worsening of one variable by no more than 30% as defined in the ACR Pedi criteria.

6.

patient/parent global assessment of disease activity

7.

Wallace criteria for CID.¹²⁴

Statistical analysis

The mean, SD, minimum, median, maximum, range and IQR for the change from baseline to 6 and 12 weeks (and each time point) for each of the continuous outcomes (JADAS-71, cJADAS-71, Physician Global Assessment of Disease activity, patient/parent global assessment, CHAQ and the number of active joints) will be presented overall and by mode of treatment received (IM injection, oral, IV infusion, intra-articular injection and two or more CS routes).

For each ACR Pedi level, the number of patients meeting the eligibility criteria will be presented overall and by mode of treatment received (IM injection, oral, IV infusion, intra-articular injection and two or more CS routes) from baseline to 6 weeks and from baseline to 12 weeks. The number and percentage of patients who have inactive disease at baseline and at 6 and 12 weeks will be presented overall and by mode of treatment received (IM injection, oral CS, IV infusion, intra-articular injection and two or more CS routes).

All available data were analysed. The proportions of missing data are presented, but owing to the nature of this study missing data were not imputed.

Participant recruitment

The first participant was registered to the SIRJIA study on 29 June 2018 and the last patient was registered on 21 September 2018. The last study visit took place on 11 January 2019.

Twelve out of the 15 sites registered at least one participant and two sites registered 10 or more participants to the study. The flow of participants through the study is presented in Figure 3.

FIGURE 3

Number of patients screened and registered in the SIRJIA.

A total of 244 patients were assessed for eligibility for the study.

The number of participants enrolled overall by site is given in Table 19. The main reasons for ineligibility included that the patient was aged ≥ 16 years (n = 27; 36%), the patient did not have a new diagnosis of JIA or flaring disease requiring induction of remission (n = 13; 17%) or the patient did not wish to give consent (n = 26; 35%).

TABLE 19

Patient recruitment by site

There were 170 patients who were eligible to participate in the study and 95 were registered.

Baseline characteristics

The demographic baseline data of the 95 participants who were registered across all centres are shown in Table 20. A total of 69 (72.6%) patients were female and the mean age of participants 9.7 years. The vast majority were described as white British (n = 84, 88.4%). Twenty-eight (29.5%) patients had recently received a new diagnosis of JIA and 67 (70.5%) had had a flare of their JIA.

TABLE 20

Baseline characteristics of patients who were registered across all centres

There were no patients who had plasma viscosity measured at baseline. Five (5.3%) patients had active uveitis. Three patients (3.2%) had fever, rash, serositis, splenomegaly or generalised lymphadenopathy that was attributable to their JIA.

A total of 37 (38.9%) clinicians considered other CS routes prior to making a final decision on the treatment route chosen. In addition, patient preference (n = 33, 34.7%), unit protocol/local practice (n = 73, 76.8%) or another factor (n = 28, 29.5%) influenced the decision made by clinicians.

Treatment

In total, 55 (57.9%) participants were treated with IACIs alone, 16 (16.8%) patients were treated with oral CSs alone and two were treated with IV infusion CSs alone. During the data collection period there were no participants who received IM injection CSs. A total of 22 patients (23.2%) received CSs by a combination of routes, with the majority of patients receiving IACIs and oral CSs (n = 9, 9.5%) or IV infusion and oral CSs (n = 8, 8.4%) (Table 21).

TABLE 21

Number of participants receiving each CS route

JADAS-71 results

The results for JADAS-71 are presented by route and overall in Table 22 for 6 weeks and in Table 23 for 12 weeks.

TABLE 22

Difference between baseline and 6-week estimates for each route of CS and overall (using all available data)

TABLE 23

Difference between baseline and 12-week estimates for each route of CS and overall (using all available data)

Overall, the mean [standard deviation (SD)] JADAS-71 score at baseline was 12.5 (10.1) and at 6 weeks had fallen by 5.9 (8.7), and by 12 weeks slightly more, by 5.4 (7). The proportion of missing data for the JADAS-71 was considerable (75%) both at 6 weeks and at 12 weeks. The main reason for missing data for the JADAS-71 at these time points was because these patients were not clinically unwell and, therefore, there was no need to carry out a blood test. The JADAS-71 requires information on all four components and, therefore, owing to missing ESR values, this could not be calculated.

The cJADAS-71 had fewer missing data at 6 weeks (26%) and at 12 weeks (22%) than the JADAS-71. The mean change in overall score at both of these time points was slightly lower in the cJADAS-71 than in the JADAS-71; the mean change for the cJADAS was 5.3 at 6 weeks and 5.4 at 12 weeks (see Table 23).

Physician global assessment and patient/parent assessment of global assessment

The overall mean Physician Global Assessment score at baseline was 3.1 and the mean change from baseline was 1.8 at both 6 and 12 weeks. The number of missing data was higher at 6 weeks (22%) than at 12 weeks (12%) (see Tables 22 and 23) because some units were unable to achieve an extra 6-week follow-up in all patients.

The overall mean Patient/Parent Assessment of Global Assessment at baseline was 3.9 and the mean change from baseline to 6 and 12 weeks was 0.9 and 0.8, respectively. Similar to the Physician Global Assessment, the number of missing data was higher at 6 weeks (25%) than at 12 weeks (20%) (see Tables 22 and 23).

Childhood Health Assessment Questionnaire

The mean CHAQ score at baseline was 0.9 and was slightly lower at 6 and 12 weeks (–0.2 and –0.3, respectively). The number of missing data at 6 weeks was higher than at 12 weeks (see Tables 22 and 23).

Number of active joints

The overall mean number of active joints at baseline was 4.2, and this reduced to 1.8 at 6 weeks and 1.3 at 12 weeks. The number of missing data at 6 weeks was again higher than at 12 weeks (see Tables 22 and 23).

Number of patients with inactive disease

There were no patients who had inactive disease at baseline. The definition of inactive disease using the Wallace criteria¹²⁴ meant that all criteria must be met at any given time point for the patient to be classified as having inactive disease. At 6 weeks there were only three (3.3%) patients who had inactive disease, and at 12 weeks there were four patients (4.4%) (Table 24).

TABLE 24

Number of patients who have inactive disease (based on the Wallace criteria) at baseline, 6 weeks and 12 weeks using all available data

There were missing data for 10 (10.5%) patients at 6 weeks and 14 (15.4%) patients at 12 weeks.

American College of Rheumatology Scores

The results of the number of patients achieving ACR Pedi 30, ACR Pedi 50, ACR Pedi 70, ACR Pedi 90 and ACR Pedi 100 at 6 weeks and 12 weeks are given in Tables 25 and 26, respectively.

TABLE 25

Number and percentage of patients meeting ACR Pedi criteria from baseline to 6 weeks

TABLE 26

Number and percentage of patients meeting ACR Pedi criteria from baseline to 12 weeks

Twenty-six (27.4%) patients could not be included in the analysis at 6 weeks and 18 (19.8%) patients could not be included at 12 weeks.

Overall, 34 (35.8%) patients achieved ACR Pedi 30, 32 (33.7%) patients achieved ACR Pedi 50, 24 (25.3%) patients achieved ACR Pedi 70, 15 (15.8%) patients achieved ACR Pedi 90 and 11 (11.6%) patients achieved ACR Pedi 100 at 6 weeks. There were similar findings at 12 weeks for each of the outcomes.