“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
SrdjanPav/E+/Getty Images
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
Dr. Dawn Wahezi
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
Dr. Lisa F. Imundo
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.