The majority of patients with newly diagnosed juvenile idiopathic arthritis achieve a health-related quality of life that is similar to that of healthy peers: results of the German multicenter inception cohort (ICON)

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic illness in children, with an incidence of 2–20 cases per 100,000 at-risk children [1]. JIA encompasses a clinically heterogeneous group of disorders with unknown causes which begin before the age of 16 years. These diseases cause both temporary and permanent disability as well as an impaired quality of life [2–4]. The treatment of JIA currently aims at achieving an inactive disease state, preventing disability and damage, and ensuring the age-appropriate development of affected children and adolescents. As JIA influences virtually all aspects of the child’s life and those of his or her family, achievement of an optimal health-related quality of life (HRQoL) is an important goal in clinical care. HRQoL is a complex, multidimensional concept that encompasses physical, emotional, social, and behavior-related well-being and functioning. A patient’s individual perception of health is affected by his/her social and cultural background as well as his/her personal value system [5–7]. Several studies [4, 8–15] have shown that JIA patients have a lower HRQoL compared with healthy controls. Most prior studies were cross-sectional in their study design [8, 12–14], and the assessment of HRQoL was often conducted several years after diagnosis [4, 11]. Longitudinal studies of HRQoL in JIA patients are rare [4, 16–18], and some were performed to examine the effects of disease-modifying antirheumatic drugs (DMARDs) [16–18].

A large Canadian inception cohort [19] investigated changes in the HRQoL of patients with JIA. They found that the HRQoL of children with JIA improved gradually over time. Another inception cohort from Scandinavia [20] found reduced physical health in only 20% of JIA patients approximately 8 years after disease onset. Some indicators of a poor quality of life have been identified [9, 21–24] and include the persistence of a high level of disease activity, the presence of disabilities, chronic pain, and low social or emotional resources. However, some questions remain unanswered; for example, it has remained unclear why patients with clinically inactive disease nevertheless report a reduced quality of life [25]. Identifying the factors that predict a poor outcome with continued low HRQoL is a vital step toward providing appropriate interventions.

To the best of our knowledge, there are no published data that evaluate the course of HRQoL in newly diagnosed JIA patients compared with healthy peers. We therefore used data from the German Inception Cohort Of patients with Newly diagnosed JIA (ICON) to investigate the HRQoL of affected children during the first years of pediatric rheumatologic care in order to: 1) describe changes in HRQoL over time; 2) compare the HRQoL of patients with that of healthy peers; and 3) identify the predictors of a suboptimal HRQoL in the course of the disease.

Our results confirm earlier findings using the ICON cohort of a noticeable reduction in disease activity in early JIA which can currently be achieved within the first 6 months of routine rheumatologic care [26]. Half of the JIA patients achieved an inactive disease status after 3 years of treatment if the cJADAS-10, which also includes the parent’s perspective, is used for assessment. A greater decrease in cJADAS-10 was associated with a greater increase in HRQoL. Parent-reported functional disability, pain, and parent global scores were significantly associated with HRQoL. The level of psychosocial health of JIA patients was comparable with that of healthy peers after 3 years of rheumatologic care, whereas a minor but significant difference remained in physical health. Different JIA categories showed unique HRQoL trajectories but, at 3-year FU, the PedsQL total scores had reached a comparable level in all categories. Three-quarters of patients with JIA reached a favorable HRQoL. Predictors of a suboptimal HRQoL (PedsQL total score < 79.3) were the parent global and pain scores at enrollment, as well as the burden borne by the family as a result of their child’s illness.

Different methods are applied to measure disease activity in JIA. We used the cJADAS-10 because of its multidimensional concept. Our findings are consistent with those of others who also observed a clear decrease in disease activity and functional limitations following treatment for recent-onset JIA [20, 39, 40].

Many studies found a lower HRQoL in patients with JIA compared with healthy controls [4, 8–15, 41]. However, their results cannot simply be transferred to recent-onset JIA patients treated in pediatric rheumatologic care since patients were often sampled in the pre-biologic era of the 1980s or 1990s [8, 11, 41] or had a disease duration of more than 10 years [4, 8, 11, 41]. It should also be considered that most of these studies were cross-sectional in nature [8, 12–15, 41] and therefore did not permit conclusions about the HRQoL in JIA patients during the course of their disease.

After 36 months of rheumatologic care, we observed a clear approximation of the patients’ PedsQL values to those of healthy peers. Regarding psychosocial health, our findings are in accordance with prior studies that found that psychosocial health was similar in patients with JIA and healthy peers [4, 10, 41, 42]. It is in line with other studies on the HRQoL of patients with JIA [4, 15] that physical health is more affected than psychosocial health, which was also shown in our analysis. Findings from the literature suggest that parents of children with health problems tend to underestimate their child’s HRQoL, whereas parents from nonclinical samples tend to report a higher HRQoL than the children themselves [43]. Considering these findings, we suppose that the convergence of PedsQL values of JIA patients to levels of age-, sex-, and SES-comparable peers is more likely to be under- rather than overestimated in our cohort.

Until now, longitudinal studies on the HRQoL of children with JIA are rare [4, 16, 19]. Oen et al. [19] investigated the HRQoL of 1249 newly diagnosed patients with JIA using the Juvenile Arthritis QoL Questionnaire (JAQQ; range 1–7). They described an improvement in median JAQQ score from 2.7 at the first visit to 1.9 at 7 months and 1.5 at 37 months after diagnosis. Similar to our data, an improvement in HRQoL was most marked within the first 6 months. We identified mean HRQoL changes that were two- to three-times higher than the corresponding minimal clinically important different PedsQL scores calculated by Varni et al. [33]. This underlines the clear clinically relevant improvement in HRQoL that was already achieved during the first months of treatment and whose level could be maintained over time.

In the ICON cohort, an improvement in HRQoL to the level measured in healthy peers was observed in each JIA category. At enrollment, each disease category differed significantly in their PedsQL total score, with particularly low scores in those patients with systemic JIA and RF-negative polyarthritis. At the onset of disease, systemic JIA is characterized by daily spiking fevers and is accompanied by a variety of other systemic signs [27] associated with a high disease burden and a decreased quality of life [8]. Patients with RF-negative polyarthritis may have low PedsQL scores at disease onset because of the restricted mobility caused by the inflammation in more than four joints. After 3 years, there were no relevant differences in HRQoL between the various JIA categories.

Our results are consistent with those reported by Oen et al. [19], who observed equivocal quality of life scores in the different JIA categories within 50 months of diagnosis. In our findings, this convergence was reached 12 months earlier. The almost equal quality of life of the different JIA categories was not found 10 years ago [8, 12, 14], which may be due to the improved effects of new treatment options. In the ICON cohort, patients with JIA were intensively treated (see [26]) according to current treatment recommendations [44–46]. Within the first year of observation, patients with systemic arthritis who received an interleukin (IL)-1 or IL-6 inhibitor most commonly achieved an inactive disease status [26] and had the highest mean PedsQL total score at the 1-year FU. In contrast, patients with psoriatic arthritis reached an inactive disease state less frequently [26] and had the lowest HRQoL scores at FU. Earlier findings [4, 41, 47] of a better HRQoL in JIA patients with inactive disease were confirmed in our study. The association between HRQoL and the clinical parameters of JIA have already been investigated in several studies [4, 9, 11, 12, 22, 48]. Significant associations between HRQoL and disease activity, physical disability, and pain have been described [4, 9, 22]. The impact of disability and pain was found to be stronger than that of disease activity in general, which is in line with our findings. Patient-reported (or, as in our study, parent-reported) outcomes were particularly associated with the patient’s HRQoL, while clinical parameters such as the physician’s global score or the number of actively involved joints played a minor role.

The proportion of JIA patients with a suboptimal HRQoL was investigated in other studies [9, 25, 49] which used a similar PedsQL cut-off to our work (< 78.6 versus < 79.3) to differentiate between optimal and suboptimal HRQOL. Lundberg et al. [49] and Haverman et al. [9] observed a suboptimal HRQoL in nearly half of their patients with JIA after a median of 2–5 and 3.6 years of disease duration, respectively. In ICON, the outcome was more favorable. Only a quarter of the patients with JIA had a suboptimal HRQoL after 3 years of rheumatologic care. We identified pain and the parent’s global assessment at enrollment as predictors of a suboptimal HRQoL status at FU. This is similar to the findings of others [4, 21, 50]. We further found that the burden caused by the disease on the child’s family is another important predictor of a suboptimal quality of life. This is in accordance with other findings [24, 51] that described an association between HRQoL and the child’s perception of social support and parental distress.

The strength of this study is the large sample size that accounts for differences in sociodemographic parameters such as age, sex, and social status between JIA patients and healthy peers. Only proxy-reported HRQoL was used to make conclusions for the whole cohort over the entire age range, rather than only in older patients and peers by self-reported HRQoL. It should be considered that proxy-reported HRQoL estimates may be biased compared with self-reports. However, the agreement between data reported by children and their parents is often high, especially in the case of sick children [47, 52]. In cases of discordance, the parents of sick patients described on average a lower HRQoL than the children themselves [43], resulting in an underestimation in HRQoL. There is another limitation that should not go unmentioned. We did not investigate the impact of individual treatment modalities on quality of life outcomes, as the ICON is an observational cohort study and treatment decisions prior to or after enrollment were confounded by their clinical indication.

With current treatment strategies, it is possible to achieve a favorable quality of life in most patients with JIA. After 3 years of pediatric rheumatology care, JIA patients have almost the same quality of life as healthy peers. This is a crucial finding for the counseling of patients and their parents. Among characteristics assessed at enrollment, family burden, pain, and functional impairment were more important than disease activity as predictors of a suboptimal quality of life over the course of this study. It is therefore important to look for these risk factors in clinical practice to be able to set the course at an early stage of the disease with targeted support measures.