Abstract
Objectives
Health outcomes in children and young people are known to vary by ethnicity and socioeconomic position. In juvenile idiopathic arthritis (JIA), it is unclear whether this relates to differential changes following one of the most common treatments, TNF-inhibitors (TNFi). This study investigated these factors, disease activity and treatment persistence following initial TNFi therapy in patients with JIA in the UK.
Methods
Patients with non-systemic JIA in the UK JIA Biologic Register starting their first TNFi biologic were included. Outcomes included change in disease activity between start of TNFi and 6 months, measured by JADAS-71. Multivariable linear regression was used to assess the association between ethnicity or socioeconomic position and change in JADAS. Treatment persistence was analysed using Kaplan–Meier estimates. Cox proportional hazards models compared TNFi drug persistence by ethnic group and by socioeconomic position.
Results
A total of 1641 patients were included: 67% female, 90% White ethnic group (6% Asian, 2% Black, 2% Mixed), 25% in the most deprived socioeconomic group. JADAS-71 improved for all ethnic and socioeconomic groups by 6 months, with no difference in improvement by group. The proportion of patients remaining on TNFi at 12 months (67%) and the likelihood of stopping was similar between all ethnic and socioeconomic groups.
Conclusion
Outcomes following TNFi initiation are similar between ethnic and socioeconomic groups. Based on the results of this study, ethnicity and socioeconomic position do not appear to be associated with differential change in disease activity, and there is no evidence that the effects of socioeconomic position are moderated by ethnicity or vice versa.
Keywords: ethnicity, socioeconomic position, juvenile idiopathic arthritis, disease activity, treatment persistence, biologic DMARD
Graphical abstract
Graphical Abstract.
Rheumatology key messages.
JIA disease activity improved over 6 months following TNFi initiation for all ethnic groups.
The proportion of JIA patients remaining on TNFi at 12 months was similar between ethnic groups.
Ethnicity does not appear to be associated with differential change in JIA disease activity.
Introduction
Juvenile idiopathic arthritis (JIA) is a group of related chronic autoimmune conditions characterized by persistent joint inflammation of unknown cause with onset before the age of 16 years [1]. JIA is diagnosed in around one in 1600 children and young people, with potential variances in incidence and prevalence between different ethnic groups [2].
JIA can lead to long-term consequences including joint damage, chronic pain and lifelong disability. These effects may significantly impact both physical and mental well-being, as well as social and economic prospects [3, 4]. However, contemporary treatment approaches have generally improved patient outcomes.
Treatment of JIA in the United Kingdom (UK) usually follows National Health Service (NHS) guidelines [5]. For children and young people with JIA for whom conventional synthetic disease-modifying antirheumatic drugs (DMARDs) do not adequately control disease, treatment with biological therapies may commence. Following the treatment pathway, for most patients, the first class of biologic used is a TNF inhibitor (TNFi). Treatment persistence is a composite real-world indicator for long-term therapeutic success, reflecting both the efficacy and tolerability of a medication.
Ethnicity and socioeconomic position have been associated with differences in access to healthcare, disease activity and disease outcomes in JIA and other conditions [6–11]. However, none have looked at the association of ethnicity and/or socioeconomic position with changes in disease activity in individuals with JIA after starting biologic therapies. Given these factors may affect outcomes generally, understanding whether they are directly associated with outcomes following initiation of biologic therapies is important in shaping appropriate care for patients.
This analysis aimed to investigate changes in disease activity and treatment persistence following initial treatment with TNFi in children and young people with JIA in the UK, by ethnic group and socioeconomic position.
Methods
Study design
This analysis used data collected through the UK JIA Biologics Register, which consists of the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort (BSPAR-ETN) and the Biologics for Children with Rheumatic Diseases (BCRD) studies. These studies share identical methodologies and data collection processes, as previously presented [12]. To summarize, since 2004 for etanercept and since 2010 for all other advanced therapies, children with JIA have been recruited at the point of starting a biologic or JAK inhibitor therapy for their JIA, in order to investigate the safety and effectiveness of these therapies.
Data collection
Baseline data, including patient demographics, JIA ILAR category [1], time since diagnosis, current disease activity measured using the JIA core outcome variables [13] and a pain visual analogue scale (VAS), and details of previous and current antirheumatic therapies were collected at the start of TNFi treatment.
Follow-up data were collected after 6 months, and 12 months, and then annually. This included changes to antirheumatic drug therapy including start/stop dates and reasons, the most recent recorded JIA core outcome variables, and adverse events. All data were captured from patient medical records at each time point as part of routine care, with no additional study visits for the purposes of data collection.
Ethnicity
Self-declared ethnicity was collected at recruitment, using the ethnicity category declared by the patient/guardian to the hospital and recorded in their medical record. For all analyses, ethnicity was grouped according to the five first-tier ethnic group categories—White, Asian, Black, Mixed and Other—according to the Office for National Statistics (ONS) England ethnic group classification [14].
Indices of deprivation
Patients were assigned to a nationwide deprivation rank using nationally published Indices of Multiple Deprivation (IMD) [15], which is a composite indicator of relative deprivation across multiple domains, based on home address postcode. IMD ranks are defined and allocated by the national statistics agency of each nation of the UK. The calculation of IMD scores differs between nations in the UK, therefore quintiles were determined separately for England (based on 2019 scores), Scotland (based on 2012 scores) and Wales (based on 2014 scores), then combined into an overall IMD quintile score; no patients were from Northern Ireland. IMD was grouped into a dichotomous variable; patients living in the most deprived quintile of addresses compared with all other patients.
Patient selection
This analysis included JIA patients who were starting their first biologic, which was a TNFi, between 1 January 2004 and 5 April 2024, registered within 6 months of starting their TNFi for whom ethnicity was recorded and at least one follow-up form had been completed. Data were extracted on 20 September 2024, and all data returned before this date was included. Patients with systemic JIA were excluded as TNFi are no longer considered the first line of biologic treatment for this subtype.
Analysis
Demographics and disease characteristics are presented at start of TNFi therapy for the total study population, and by ethnic group and IMD group. Counts of fewer than five patients are suppressed due to requirements of non-disclosure under GDPR.
Outcomes following initial treatment with first TNFi
For analyses of change in disease activity, patients were additionally required to have at least one measure of disease activity recorded no more than 6 months before commencing TNFi treatment as part of their baseline assessment.
The primary outcome was the mean change in Juvenile Arthritis Disease Activity Score [16], based on 71 joint-count (JADAS-71) between TNFi treatment initiation and after 6 months of follow-up; outcomes were presented regardless of whether a patient remained on treatment. The JADAS-71 is a composite score, calculated by summing the Active Joint Count (AJC), Physician’s Global Assessment of overall disease activity (PGA), Patient/Parent Global Evaluation of overall wellbeing (PGE) and normalized erythrocyte sedimentation rate (ESR), giving a final total score between 0 (low disease activity) and 101 (very high disease activity).
Secondary outcomes included disease activity outcomes after 6 months of treatment: (i) the proportion of patients attaining minimal disease activity (MDA, Supplementary Table S1) [17]; (ii) proportion of patients attaining ACR paediatric 30%, 50%, 70% and 90% responses (ACR-Pedi-30/50/70/90), modified to allow for low baseline disease activity scores (Supplementary Table S2); (iii) mean change in clinical JADAS-71 (cJADAS-71) – composite score excluding ESR [18]; (iv) mean change in each of AJC, limited joint count (LJC), PGA, PGE, Childhood Health Assessment Questionnaire of functional ability (CHAQ) [19, 20], ESR and patient/parent reported pain (scale 0–10).
The association between ethnicity, IMD and change in JADAS-71 from start of TNFi therapy to after 6 months of treatment was analysed using multivariable linear regression, adjusted for gender, age, time between diagnosis and commencement of TNFi treatment, year of treatment start, ILAR category, history of uveitis, use of glucocorticoids at start of treatment and baseline JADAS-71; these covariates were chosen a priori in advance. An interaction term between ethnic group and IMD was included in the model.
Persistence of TNFi treatment
All patients were included in analysis of drug persistence over the first 12 months of treatment with a TNFi.
Kaplan–Meier estimates were used to analyse treatment persistence of a patient’s first TNFi. Patients entered the model at the start of TNFi treatment and were considered to remain on drug until stopping their first TNFi for any reason other than for remission, date of last follow-up, death or 12 months from commencement of TNFi, whichever was earliest. Patients were censored if they stopped TNFi reporting remission as the stop reason. Kaplan–Meier curves of TNFi persistence up to 12 months by ethnic group and by IMD are presented, and the proportion of patients remaining on TNFi at 12 months was estimated. Cox proportional hazards models were used to compare TNFi drug persistence by ethnic group and by IMD, adjusted for gender, age, time between diagnosis and commencement of TNFi treatment, history of uveitis, ILAR category and an interaction term between ethnicity and IMD. A sensitivity analysis of only patients starting initial TNFi from 2010 onwards was completed to account for the limited availability and choice of drug of biologic therapies prior and the impact that may have on treatment persistence.
Missing data
IMD data were not available for all participants; analyses including IMD as a covariable were therefore restricted to participants with recorded IMD values. Multiple imputation using chained equations (72 datasets) was used to account for missing disease activity and covariate data for patients where IMD was available. Complete variables included in the imputation model included age, gender, ethnic group, IMD, history of uveitis, drug and ILAR category. Imputed disease activity variables included AJC, LJC, PGA, PGE, CHAQ, ESR and pain, at both baseline and at six months. JADAS-71 and cJADAS-71 (at baseline and six months) and change in JADAS-71 and cJADAS-71, MDA and ACR-Pedi-30/50/70/90 were calculated using imputed variables.
Analysis was performed using Stata Version 14.0.
Patient involvement
Prior to this analysis the authors discussed the proposed project with parents of children and young people with JIA, from a diverse range of ethnic backgrounds. Their role was to help identify priorities for analysis and develop the analysis plan. Parent involvement was conducted through online discussion groups and interviews with the lead author, with priorities for analysis collated into the initial analysis plan which parents then reviewed and revised. This analysis is thus informed by the needs of patients and families, reflecting the identities and interests of a diverse population. Whether disease outcomes in JIA are associated with ethnicity and social determinants of health was reported to be a priority area to investigate by families. Patient involvement supported the development of both this analysis and a previous analysis regarding outcomes following methotrexate [21].
Ethical approval
Both BCRD and BSPAR-ETN have UK Health Research Authority ethical approval and all parents (and, where appropriate, patients) gave informed written consent in accordance with the Declaration of Helsinki. No further ethics approval was required to undertake the current analysis.
Results
Baseline characteristics
A total of 1641 children and young people with JIA starting their first biologic as a TNFi met the inclusion criteria and were included in this analysis (Supplementary Fig. S1). Of these, 67% were female, 90% were in the White ethnic group (6% Asian, 2% Black, and 2% Mixed ethnicity), and 25% were in the most deprived IMD quintile (Table 1). The proportion of patients of White ethnicity was slightly higher than national population estimates by ethnicity for children under the age of 16 [22] (90% in this analysis, compared with 73% of the population and 83% of incident JIA cases; Supplementary Table S3). At the start of TNFi treatment, the median age was 11 years (inter-quartile range, IQR: 7–14 years) and median time between diagnosis and start of TNFi was 2 years (IQR: 1–5). The most frequent ILAR category for all ethnic groups was rheumatoid factor (RF) negative polyarthritis (37% of all patients, range 30–37% by ethnic group). The majority of patients started etanercept (68%) followed by adalimumab (29%) with fewer starting on infliximab (4%); this did not differ by ethnic group.
Table 1.
Baseline characteristics of 1641 children and young people with JIA commencing first TNFi (included in the drug persistence analysis).
| Characteristic | Whole cohort | Ethnic group |
IMD group |
|||||
|---|---|---|---|---|---|---|---|---|
| White | Asian | Black | Mixed | Most deprived quintile | All others | |||
| N (row %) | 1641 | 1481 (90) | 97 (6) | 27 (2) | 36 (2) | 332 (25) | 972 (75) | |
| Gender, n (%) | Male | 538 (33) | 483 (33) | 29 (30) | 12 (44) | 14 (39) | 106 (32) | 314 (32) |
| Female | 1103 (67) | 998 (67) | 68 (70) | 15 (56) | 22 (61) | 226 (68) | 658 (68) | |
| Age at start of TNFi | Median (IQR) | 11 (7, 14) | 11 (7, 14) | 12 (8, 14) | 12 (8, 14) | 10 (5, 14) | 10 (7, 13) | 11 (7, 14) |
| Disease duration (time between diagnosis and commencement of TNFi), years | Median (IQR) | 2 (1, 5) | 2 (1, 5) | 2 (1, 4) | 2 (1, 6) | 2 (1, 3) | 2 (1, 5) | 2 (1, 5) |
| TNFi, n (%) | Etanercept | 1114 (68) | 1010 (68) | 64 (66) | 16 (59) | 24 (67) | 233 (70) | 594 (61) |
| Adalimumab | 468 (29) | 423 (29) | 26 (27) | 11 (41) | 8 (22) | 84 (25) | 340 (35) | |
| Infliximab | 59 (4) | 48 (3) | 7 (7) | 0 (0) | 4 (11) | 15 (5) | 38 (4) | |
| Start year of TNFi, n (%) | Pre-2010 | 500 (30) | 468 (32) | 23 (24) | 4 (15) | 5 (14) | 81 (24) | 199 (20) |
| 2010–2015 | 521 (32) | 453 (31) | 38 (39) | 10 (37) | 20 (56) | 126 (38) | 339 (35) | |
| 2016 onwards | 620 (38) | 560 (38) | 36 (37) | 13 (48) | 11 (31) | 125 (38) | 434 (45) | |
| Indices of Multiple Deprivation (IMD) quintile, n (%) | 1—Most deprived | 332 (25) | 276 (23) | 33 (42) | 12 (62) | 10 (34) | — | — |
| 2 | 220 (17) | 193 (16) | 20 (25) | <5 | < 5 | — | — | |
| 3 | 264 (20) | 245 (21) | 12 (15) | <5 | 6 (21) | — | — | |
| 4 | 234 (18) | 218 (19) | <5 | <5 | <5 | — | — | |
| 5—Least deprived | 254 (19) | 243 (21) | <5 | <5 | 8 (28) | — | — | |
| ILAR category, n (%) | Persistent oligo | 195 (12) | 168 (11) | 17 (18) | 5 (19) | 5 (14) | 38 (11) | 135 (14) |
| Oligo extended | 336 (20) | 319 (22) | 6 (6) | 5 (19) | 6 (17) | 80 (24) | 192 (20) | |
| Poly RF- | 601 (37) | 546 (37) | 35 (36) | 8 (30) | 12 (33) | 108 (33) | 360 (37) | |
| Poly RF+ | 156 (10) | 133 (9) | 16 (16) | <5 | <5 | 30 (9) | 88 (9) | |
| Psoriatic | 108 (7) | 100 (7) | 6 (6) | <5 | <5 | 31 (9) | 55 (6) | |
| Enthesitis-related | 188 (11) | 168 (11) | 9 (9) | 5 (19) | 6 (17) | 32 (10) | 121 (12) | |
| Undifferentiated | 57 (3) | 47 (3) | 8 (8) | <5 | <5 | 13 (4) | 21 (2) | |
| History of chronic anterior uveitis at start of treatment, n (%) | Yes | 303 (20) | 268 (19) | 20 (22) | 8 (32) | 7 (21) | 58 (18) | 194 (21) |
| No | 1222 (80) | 1109 (81) | 69 (78) | 17 (68) | 27 (79) | 256 (82) | 726 (79) | |
IMD: Index of Multiple Deprivation; IQR: interquartile range; time to registration: time (years) between diagnosis of JIA and registration and commencement of treatment.
A total of 1418 patients met the additional inclusion criteria for analyses of disease activity (67% female; 90% White ethnic group, 6% Asian, 2% Black, 3% Mixed ethnicity; 25% in the most deprived IMD quintile; Supplementary Table S5). This cohort appeared broadly similar to the whole group of 1641 patients included in the drug persistence analysis in all demographic features. Missingness is presented in Supplementary Table S6.
Outcomes following initial treatment with first TNFi
Following treatment with TNFi for 6 months, disease activity had improved for all ethnic groups (Table 2). Mean change in JADAS-71 at six months (95% CI) was broadly similar for all ethnic groups: –8.9 units (–9.5, –8.3) for patients of White ethnicity, –6.8 (–9.0, –4.7) for patients of Asian ethnicity, –12.7 (–19.3, –6.2) for patients of Black ethnicity and –7.9 (–10.7, –5.2) for patients of Mixed ethnicity. The two IMD dichotomized groups (see above) both showed similar improvement in JADAS: most deprived quintile –7.7 (–8.7, –6.5), all others –8.4 (–9.1, –7.7). Both unadjusted and adjusted relative mean change in JADAS-71, relative to White ethnicity, were similar for Asian, Black and Mixed children and young people, and similar for both IMD groups.
Table 2.
Change in JADAS-71 between baseline and six months after initiation of TNFi treatment amongst 1418 children and young people with JIA by ethnic group and socioeconomic position.
| Variable | Ethnic group |
IMD group |
||||
|---|---|---|---|---|---|---|
| White | Asian | Black | Mixed | Most deprived quintile | All others | |
| N | 1272 | 86 | 24 | 36 | 282 | 848 |
| JADAS-71 | ||||||
| Baseline, mean (95% CI) | 13.8 (13.2, 14.4) | 13.4 (11.3, 15.6) | 17.6 (11.2, 23.9) | 12.3 (9.9, 14.7) | 12.7 (11.6, 13.7) | 13.1 (11.6, 13.7) |
| 6 months, mean (95% CI) | 4.9 (4.6, 5.3) | 6.6 (4.9, 8.2) | 4.8 (2.6, 7.1) | 4.4 (2.7, 6.1) | 5.1 (4.4, 5.7) | 4.7 (4.3, 5.1) |
| Change, mean (95% CI) | −8.9 (−9.5, -8.3) | −6.8 (−9.0, −4.7) | −12.7 (−19.3, −6.2) | −7.9 (−10.7, −5.2) | −7.7 (−8.7, −6.5) | −8.4 (−9.1, −7.7) |
| Relative mean change (95% CI) | Reference | 2.1 (−0.3, 4.5) | 0-3.8 (−8.3, 0.07) | 1.0 (−2.7, 4.6) | 0.8 (−0.6, 2.2) | Reference |
| Adjusted relative mean (95% CI) | Reference | 1.9 (−0.1, 3.8) | −0.9 (−3.4, 5.2) | −0.5 (−3.2, 2.2) | 0.4 (−0.4, 1.3) | Reference |
| 6-month outcomes | ||||||
| MDA, % (95% CI) [n] | 54 (50, 57) [1150] | 43 (31, 56) [77] | 51 (25, 77) [19] | 61 (42, 81) [30] | 52 (45, 59) [254] | 55 (51, 60) [738] |
| ACR-Pedi-30 response | 39 (36, 42) | 29 (19, 39) | 37 (17, 56) | 49 (33, 66) | 38 (32, 43) | 40 (37, 43) |
| ACR-Pedi-50 response | 38 (35, 40) | 29 (19, 39) | 36 (17, 56) | 45 (28, 61) | 36 (30, 42) | 39 (35, 42) |
| ACR-Pedi-70 response | 34 (31, 37) | 21 (12, 30) | 33 (14, 52) | 37 (20, 53) | 31 (26, 37) | 36 (33, 39) |
| ACR-Pedi-90 response | 28 (26, 31) | 20 (11, 28) | 29 (11, 47) | 33 (17, 48) | 26 (21, 31) | 30 (27, 34) |
MDA defined as: persistent-oligoarthritis PGA ≤2.5 cm and 0 AJC; Enthesitis-related JIA (ERA) were excluded as MDA is not validated for these patients; all other ILAR subtypes PGA ≤3.4 cm, PGE ≤2 cm and AJC ≤1 [26]. n for MDA is shown in square brackets, as it excludes patients with ERA.
IMD: Index of Multiple Deprivation; MDA: minimal disease activity.
The proportion of children and young people who achieved minimal disease activity (MDA) following 6 months of TNFi treatment was similar between ethnic groups and IMD groups (Table 2). The proportions attaining ACR-Pedi-30/50/70/90 responses were also similar across ethnic groups (the latter ranging from 20% to 33% by ethnic groups).
In the multivariable linear regression investigating change in JADAS-71 after 6 months of TNFi treatment (Supplementary Table S7; 1130 patients with complete IMD data available included in the model), neither ethnicity nor IMD were statistically significantly associated with change in JADAS-71 score. The interaction between ethnicity and IMD was not significant.
All ethnic groups and the dichotomized IMD groups showed an improvement in each of AJC, LJC, PGA, PGE, CHAQ, ESR and pain over time (Supplementary Table S8).
Persistence of TNFi treatment
Kaplan–Meier survival curves for TNFi treatment persistence up to 12 months are shown by ethnic group (Fig. 1) and IMD group (Fig. 2). Overall, 67% of patients remained on TNFi at 12 months (95% CI 66%, 68%); this was similar between ethnic groups and IMD groups (Table 3). Median treatment survival was 1.2 years (95% CI 0.8, 2.2 years). The adjusted hazard ratios identified no differences in treatment persistence across ethnic groups, nor between IMD groups. Similar results were seen in an analysis limited to those starting their first TNFi from 2010 onwards (median treatment survival 1.2 years); patients in this sensitivity analysis were similar to the full cohort (Supplementary Table S4).
Figure 1.
Kaplan–Meier survival curve for first TNFi treatment for 1641 children and young people with JIA by ethnic group: White (N = 1481); Asian (N = 97); Black (N = 27); and Mixed (N = 36)
Figure 2.
Kaplan–Meier survival curve for first TNFi treatment for 1304 children and young people with JIA by Index of Multiple Deprivation (IMD) group (for whom IMD data were available); those in the most deprived quintile (N = 332) compared with all other patients (N = 972)
Table 3.
Hazard ratio for treatment survival of first TNFi treatment amongst 1641 children and young people with JIA by ethnic group and IMD.
| Ethnic group |
IMD group |
|||||
|---|---|---|---|---|---|---|
| White | Asian | Black | Mixed | Most deprived quintile | All others | |
| All patients | ||||||
| N | 1481 | 97 | 27 | 36 | 332 | 972 |
| Percentage remaining on TNFi (95% CI) | 67 (66, 68) | 68 (64, 73) | 75 (67, 83) | 59 (51, 67) | 64 (62, 66) | 67 (66, 68) |
| Unadjusted hazard ratio (95% CI) | Reference | 0.96 (0.60, 1.52) | 0.50 (0.16, 1.57) | 1.46 (0.78, 2.74) | 1.07 (0.83, 1.38) | Reference |
| Adjusted hazard ratio (95% CI) | Reference | 0.95 (0.58, 1.56) | 0.62 (0.20, 1.93) | 1.20 (0.57, 2.55) | 1.08 (0.83, 1.37) | Reference |
| Sensitivity analysis a | ||||||
| N | 1013 | 74 | 23 | 31 | 251 | 773 |
| Percentage remaining on TNFi (95% CI) | 65 (64, 66) | 68 (63, 73) | 74 (66, 83) | 58 (49, 67) | 64 (62, 67) | 65 (64, 67) |
| Unadjusted hazard ratio (95% CI) | Reference | 0.87 (0.60, 1.26) | 0.71 (0.33, 1.49) | 1.44 (0.91, 2.28) | 1.07 (0.87, 1.31) | Reference |
| Adjusted hazard ratio (95% CI) | Reference | 1.06 (0.71, 1.59) | 0.91 (0.41, 2.07) | 1.23 (0.72, 2.11) | 1.14 (0.92, 1.41) | Reference |
Adjusted hazard ratio adjusted for age, gender, grouped ILAR subclass, IMD group and time between diagnosis and commencement of TNFi treatment. aSensitivity analysis includes only patients starting first TNFi from 2010 onwards.
| Centre | Principal Investigator |
| (Adult) Broadgreen Hospital | Dr Devesh Mewar |
| (Adult) Chapel Allerton Hospital | Dr Helen Marzo-Ortego |
| (Adult) Freeman Hospital | Dr Flora McErlane |
| (Adult) Manchester Royal Infirmary | Dr Ben Parker |
| (Adult) Minerva Health Centre (Lancashire) | Dr Elizabeth MacPhie |
| (Adult) New Cross Hospital | Dr Srinivasan Venkatachalam |
| (Adult) Pinderfields Hospital | Dr Sharmin Nizam |
| (Adult) Queens Medical Centre, Nottingham | Dr Ian Gaywood |
| (Adult) Royal Hallamshire Hospital | Dr Rachel Tattersall |
| (Adult) Russells Hall Hospital | Dr Niki Erb |
| (Adult) Stepping Hill Hospital | Dr Abbas Ismail |
| (Adult) University College London Hospital | Dr Coziana Ciurtin/Dr Debajit Sen |
| (Adult) University Hospital Aintree | Professor Robert Moots |
| (Adult) Wishaw General Hospital | Dr Elizabeth Murphy |
| (Adult) Wrightington Hospital | Dr Easwaradhas Gladston-Chelliah |
| (Adult) York Hospital | Dr Mark Quinn |
| Addenbrookes Hospital | Dr Kate Armon |
| Alder Hey Hospital, Liverpool | Dr Michael Beresford/Dr Liza McCann |
| Ashford and St Peters Hospital | Dr Gillan Bask/Lorna Walding/Susan Marchant |
| Basildon Hospital, Essex | Dr Nagui Gendi |
| Birmingham Children’s Hospital | Dr Eslam Al-Abadi |
| Bradford Royal Infirmary | Charlene Bass Woodcock |
| Bristol Royal Hospital for Children | Dr Athimalaipet Ramanan |
| Cheltenham General Hospital | Dr Louise Walker |
| Chesterfield Royal Hospital | Dr John Bourne |
| Crosshouse Hospital, Kilmarnock | Dr Bridget Oates |
| Derbyshire Children’s Hospital | (site no longer active) |
| Derriford Hospital, Plymouth | Dr Vicky Ohlsson |
| Diana Princess of Wales Hospital, Grimsby | Dr David James |
| Evelina London Children’s Hospital | Dr Nick Wilkinson |
| George Eliot Hospital | Dr Kathy Bailey |
| Great North Children’s Hospital Newcastle | Dr Flora McErlane |
| Great Ormond Street Hospital, London | Dr Ovgu KulCinar |
| Hinchingbrooke Hospital, Huntingdon | Dr Gill Pountain |
| King’s Mill Hospital | Dr Mitra |
| Leeds General Infirmary | Dr Mark Wood |
| Leicester Royal Infirmary | Dr Arani Sridhar |
| New Cross Hospital, Wolverhampton | Dr Karen Davies |
| Norfolk and Norwich University Hospital | Dr Kate Armon |
| Northampton General Hospital | Dr Rachel Jeffery/Imogen Norton |
| Nuffield Orthopaedic Centre, Oxford | Dr Kathy Bailey |
| Peterborough City Hospital | Dr Afraa Al-Sabbagh |
| Poole Hospital | Dr Fouz Rahmeh |
| Queen Alexandra Hospital, Portsmouth | Dr Joanne Borbone |
| Queen Elizabeth Hospital, Woolwich | (site no longer active) |
| Queen Elizabeth the Queen Mother Hospital, Margate | Dr Alison Leak |
| Queen’s Medical Centre, Nottingham | Dr Rangaraj Satyapal/Dr Kishore Warrier |
| Royal Aberdeen Children’s Hospital | Dr Gulshan Malik |
| Royal Derby Hospital | Dr Richard Bowker |
| Royal Devon and Exeter Hospital | Dr Nigel Osborne |
| Royal Hospital for Children & Young People, Edinburgh | Dr Catriona Anderson |
| Royal Hospital for Children, Glasgow | Dr Jo Walsh |
| Royal Manchester Children’s Hospital | Dr Alice Chieng |
| Royal Shrewsbury Hospital | Dr Richard Brough |
| Royal Stoke University Hospital | Dr Jonathon Packham/Dr Alex Tabor |
| Sheffield Children’s Hospital | Dr Daniel Hawley |
| Sheffield Children’s Hospital | Dr Daniel Hawley |
| Southampton General Hospital | Dr Alice Leahy |
| Southend University Hospital | Dr Rajesh Rawlani |
| Staffordshire Rheumatology Centre | Dr Jon Packham |
| Tayside Children’s Hospital | Dr Jo Walsh |
| The Great Western Hospital | Dr Rosemary Waller |
| The Robert Jones & Agnes Hunt Orthopaedic Hospital | Dr Karen Davies |
| University Hospital Coventry | Dr Willam Coles |
| University Hospital Wales, Cardiff | Dr Jeremy Camilleri |
| Worthing Hospital | Dr Lisa Bray |
Discussion
This is the first study specifically investigating changes in disease activity and treatment persistence following first TNFi treatment in children and young people with JIA by ethnic group and socioeconomic position. Overall, following TNFi treatment children and young people with JIA showed improvements in all analysed measures of disease activity. Reassuringly there was no evidence that improvements differed significantly by ethnic group or by socioeconomic position in this analysis. Additionally, duration on first TNFi (used as a surrogate marker of controlled disease) was not associated with ethnic group or socioeconomic position.
While around 61% of children and young people with JIA remain on methotrexate after one year of treatment [21], a significant proportion progress to biologic therapies. TNFi were the first biologic therapies licensed for use in JIA [23], and with their established efficacy and safety profile, remain the most frequently prescribed class of biologic treatments for children and young people with JIA [24]. Whilst previous studies have considered disease outcomes of patients with JIA [12], to date the possible association with social determinants of health have not been considered.
This study has found improvements in disease activity over the first six months, measured by the JADAS-71, for all ethnic groups and IMD groups following TNFi initiation. These improvements took place alongside improvements in individual core outcome variables including active and limited joint counts, physician’s assessment of overall disease activity, patient/parent evaluation of overall wellbeing, functional ability, laboratory inflammatory markers and patient-reported pain. Importantly, these measures at both start of therapy and after 6 months (including change in disease activity), were similar between all ethnic groups and IMD groups. In addition, around half of patients in this study attained minimal disease activity by 6 months after starting treatment with a TNFi, regardless of their ethnic group or IMD group. This is a higher proportion than attained by treatment-naive patients commencing treatment with methotrexate (45%) [21]. The proportion of patients attaining ACR-Pedi was similar between groups; the proportion attaining ACR-Pedi was similar to that following methotrexate [21].
This study is based on data from a national cohort study following patients over time monitoring treatment and disease activity. Whilst it seeks to be broadly representative of the whole UK JIA population, it appears that children and young people of White ethnicity may be over-represented in this analysis. It is not possible to determine whether this is due to selection bias at recruitment, or differences in prescribing patterns and/or treatment uptake. Children from the most deprived groups are slightly over-represented in this analysis (25%, compared with an expected 20% of the population as a whole), and 19% of children and young people with a diagnosis of JIA [25].
Limitations of this study include the relatively small sample size within the Asian, Black and Mixed ethnic groups. These small numbers lead to increased variability and decreased statistical power, limiting our ability to make broader conclusions. Additionally, some outcome measures had a high level of missing data, which may affect the precision of estimates, although the use of multiple imputation sought to minimize the impact of selection bias, and analysis models were adjusted for patient characteristics at the start of TNFi treatment to account for any measured confounding. The analyses did not include an assessment of safety or occurrence of adverse events, which would add to this evidence base. The relatively small number of patients meant that year of starting TNFi had to be grouped into bands, although the sensitivity analysis of drug persistence, restricted to patients starting TNFi after 2010, did not indicate differences compared with whole cohort.
Nonetheless, it appears that in this group of children and young people with JIA, outcomes following TNFi initiation are similar across ethnic and IMD groups. Ethnicity and IMD do not appear to be associated with significant differences in disease activity over time, and there was no evidence that any potential effects of IMD status are moderated significantly by ethnicity or vice versa. Whilst further research to identify potential differences associated with social determinants of health are warranted, the findings of this study—that there is no apparent difference in outcomes following TNFi initiation based on ethnicity and socioeconomic position—should be of reassurance to prescribers and patients starting TNFi.
Supplementary Material
Acknowledgements
The BSR has previously received restricted income from Pfizer to fund the BSPAR Etanercept Cohort. This income financed a wholly separate contract between BSR and the University of Manchester who provide and oversee the data collection, management and analysis of the data. The chief investigator and her team have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution. The authors would like to acknowledge the Centre for Epidemiology Versus Arthritis (Arthritis Research UK Grant No. 21755), who provided the infrastructure support for the study, and the NIHR Manchester Biomedical Research Centre (NIHR203308) for co-funding of infrastructure support. L.K.F. is additionally supported by Arthritis UK (23126). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Access to the underlying identifiable and potentially re-identifiable pseudonymized electronic health record data is tightly governed by various legislative and regulatory frameworks and restricted by best practice. We would like to thank the patients, rheumatology and research nurses, and clinicians who have helped support this study, the original British Society for Paediatric and Adolescent Rheumatology (BSPAR) Consensus Group for Prescription of Biologics in Children (established in 2004), the BSPAR Clinical Affairs Committee and the NIHR CRN: Children/Arthritis Research UK Paediatric Rheumatology Clinical Studies Group for their generous support in the establishment of these registers. The recruiting centres were supported by the National Institute for Health Research (NIHR) Clinical Research Network in England. The following is the list of collaborators for the UK JIA Biologics Register and includes the Biologics for Children with Rheumatic Diseases (BCRD) study and the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN).
Contributor Information
Richard P Beesley, Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Eileen Baildam, The Alexandra Hospital, Cheadle, Manchester, United Kingdom.
Michael W Beresford, Department of Paediatric Rheumatology, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom; Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Sharon Douglas, Scottish Network for Arthritis in Children (SNAC), Isle of Arran, United Kingdom.
Taunton R Southwood, Institute of Child Health, University of Birmingham, Birmingham, United Kingdom.
Kimme L. Hyrich, Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom National Institute of Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Jenny H. Humphreys, Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom National Institute of Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Lianne Kearsley-Fleet, Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
the UK JIA Biologics Register:
Devesh Mewar, Helen Marzo-Ortego, Flora McErlane, Ben Parker, Elizabeth MacPhie, Srinivasan Venkatachalam, Sharmin Nizam, Ian Gaywood, Rachel Tattersall, Niki Erb, Abbas Ismail, Coziana Ciurtin, Debajit Sen, Professor Robert Moots, Elizabeth Murphy, Easwaradhas Gladston-Chelliah, Mark Quinn, Kate Armon, Michael Beresford, Liza McCann, Gillan Bask, Lorna Walding, Susan Marchant, Nagui Gendi, Eslam Al-Abadi, Charlene Bass-Woodcock, Athimalaipet Ramanan, Louise Walker, John Bourne, Bridget Oates, Vicky Ohlsson, David James, Nick Wilkinson, Kathy Bailey, Flora McErlane, Ovgu KulCinar, Gill Pountain, Mitra, Mark Wood, Arani Sridhar, Karen Davies, Kate Armon, Rachel Jeffery, Imogen Norton, Kathy Bailey, Afraa Al-Sabbagh, Fouz Rahmeh, Joanne Borbone, Alison Leak, Rangaraj Satyapal, Kishore Warrier, Gulshan Malik, Richard Bowker, Nigel Osborne, Catriona Anderson, Jo Walsh, Alice Chieng, Richard Brough, Jonathon Packham, Alex Tabor, Daniel Hawley, Daniel Hawley, Alice Leahy, Rajesh Rawlani, Jon Packham, Jo Walsh, Rosemary Waller, Karen Davies, Willam Coles, Jeremy Camilleri, and Lisa Bray
Supplementary material
Supplementary material is available at Rheumatology online.
Data availability
The data underlying this article cannot be shared publicly to maintain the privacy of the individuals who participated in the study. The data that support the findings of this study are available via application to the UK JIA Biologics Register Scientific Steering Committee (via the corresponding author). Restrictions apply to the availability of these data.
Contribution statement
All authors have provided substantial contributions to the conception or design of the work, the acquisition of the data, and the interpretation of data. R.P.B. performed the statistical analysis, and L.K.F., K.L.H. and J.H.H. contributed to the analysis interpretation; all directly accessed and verified the underlying data reported in the manuscript. R.P.B. wrote the first draft. All other authors participated in the final drafting of the work or revising it critically for important intellectual content. All authors contributed to the final approval of the published version.
Funding
The UK JIA Biologics Register—including the Biologics for Children with Rheumatic Diseases (BCRD) study and the BSPAR Etanercept Cohort (BSPAR-ETN) study—is jointly funded by the British Society for Rheumatology (BSR) and Arthritis UK (previously Versus Arthritis; UK grant number 20747) via a research grant to the University of Manchester. No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. K.L.H. and J.H.H. are additionally supported by the NIHR Manchester Biomedical Research Centre [NIHR203308]. J.H.H. is additionally supported by the Academy of Medical Sciences Starter Grant for Clinical Lecturers [SGL020\1047]. L.K.F. is additionally support by Arthritis UK (23126). The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in the study design, data collection, data analysis, data interpretation or preparation of this manuscript. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.
Disclosure statement: R.B. is the founder and Director of the charity Juvenile Arthritis Research. K.L.H. has received honoraria from Abbvie for speaking at educational conferences and has received grant income from Pfizer and BMS for research separate to that presented in this paper. None of the other authors have any conflicts of interest in respect of this paper.
The preliminary analysis from this study was presented at EULAR Congress 2025 https://doi.org/10.1016/j.ard.2025.06.421.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data underlying this article cannot be shared publicly to maintain the privacy of the individuals who participated in the study. The data that support the findings of this study are available via application to the UK JIA Biologics Register Scientific Steering Committee (via the corresponding author). Restrictions apply to the availability of these data.