Changing Treatment Patterns for Patients with JIA

Over an 18-year period, Mia Glerup, MD, PhD, clinical associate professor of pediatrics, Aarhus University, Denmark, and colleagues explored the sustainability of remission in patients with juvenile idiopathic arthritis (JIA). The researchers found that although significantly more patients were off medication at the 18-year follow-up than at the 8-year follow-up, remission rates remained stable, with approximately half of study participants in remission. The study, published in the May 2022 issue of Arthritis Care & Research, also revealed the distribution of patients in the International League of Associations for Rheumatology (ILAR) JIA categories changed significantly throughout the study period.¹

Study Details

The investigators analyzed data from the prospective, longitudinal, population-based Nordic JIA cohort, focusing on patients with disease onset between 1997 and 2000. They invited all patients to three visits during the 18-year study period: baseline, year 8 and year 18. The researchers leveraged a combination of in-clinic and phone interviews to support a high level of participation in the study, resulting in 510 patients with baseline data, 450 patients with follow-up data at 8 years (88%) and 422 patients with follow-up data at 18 years (83%). At each time point, the researchers collected clinical data related to treatment, disease activity and ILAR category.

Of the 373 participants who had a follow-up visit at all three time points, 273 (73.2%) were not receiving disease-modifying anti-rheumatic drugs (DMARDs) at baseline. At the 8-year follow-up, 59.7% of the participants were not receiving DMARDs and at the 18-year follow-up this proportion increased significantly to 70.0% (reference range [RR] 1.3, P=0.003).

At the 8-year follow-up, almost 60% of participants were off all medication, and at the 18-year follow-up 70% were off all medication—a rate that remained stable between 8 and 18 years after disease onset. The investigators then examined remission status in patients who were off medication and compared it to remission status of patients who were on medication. To define remission, the investigators used the Wallace criteria for clinical active disease, which include:

• No joints with active disease;

  • No fever, rash, serositis, splenomegaly or generalized lymphadenopathy attributable to JIA;

  • No active uveitis;

  • Normal erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) level; and

  • A physician global assessment of the disease activity (PGA), with the best score attainable indicating no disease activity.

Patients on medication achieved clinical remission when they fulfilled the criteria for inactive disease on systemic anti-inflammatory medication for a minimum of six continuous months. For clinical remission in patients off medication, the patients had to have inactive disease for a continuous period of at least 12 months off all anti-arthritis and anti-uveitis medication. During the 18 years of follow-up, approximately half of the patients achieved remission, 52% in the off-medication group vs. 51% in the on-medication group.

According to the ILAR consensus-based classification criteria, there are seven exclusive JIA categories, including systemic JIA, oligoarthritis (persistent and extended), polyarticular rheumatoid factor (RF) negative, polyarticular RF positive, juvenile psoriatic, enthesitis-related (ERA) and undifferentiated. Previous research has shown the distribution of patients for most categories tends to change over time in the first decade of the disease course.² Likewise, in the current study, the investigators found 12% of the patients changed ILAR category between 8 and 18 years after disease onset. Approxi­mately half of the shifts between ILAR categories were the result of updated information on ankylosing spondylitis, psoriasis or acute anterior uveitis in a first-degree relative.

Balanced Optimism

Noting that many of the patients achieved drug-free remission during the 18-year study period, Daniel J. Lovell, MD, MPH, Joseph E. Levinson Endowed Chair of pediatric rheumatology at Cincinnati Children’s Hospital Medical Center, says, “The results are really optimistic.”

Dr. Lovell expressed surprise that the rate of remission remained stable from the 8-year to the 18-year follow-up because biologic DMARDs became the standard of care during that time. He explains the first biologics were approved in the U.S. for the treatment of JIA in 2000 and, although he expected the uptake in their use to be gradual, the Scandinavian cohort appears undertreated with biologic DMARDs relative to current recommendations, which call for early aggressive treatment.³

“Perhaps it is an undertreated group,” says Dr. Lovell, referring to the fact that half of the patients had not achieved remission, “but there are still a large number of patients who achieved drug-free remission.”

Dr. Yukiko Kimura, MD, chief of the Pediatric Rheuma­tology Division at the Joseph M. Sanzari Children’s Hospital, Hackensack University Medical Center, N.J., says, “Practically speaking, looking at the results from a less optimistic perspective, this study shows that many JIA patients continue to have active disease even into adulthood, despite the belief that many with JIA ‘grow out of it.’ The study needs to be interpreted with caution because a significant number of patients did not have a follow-up at 8 and/or 18 years after diagnosis. Moreover, because JIA is not one disease, the outcome will be different depending on which JIA disease you have.”

Need to Revise ILAR Criteria

The current ILAR criteria require a patient’s JIA subtype be changed based on the development of new-onset rheumatic diseases among first-degree relatives even when there has been no change in the patient’s arthritis.³ According to Dr. Lovell, this requirement likely accounted for much of the change in JIA subtype.

“There are movements afoot to revise the ILAR criteria,” says Dr. Lovell.^4,5

Dr. Kimura says, “We know that the ILAR classification is not an accurate way of diagnosing JIA categories based on biology, and that many patients do not stay in one category as time goes on.”

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

References

1. Glerup M, Arnstad ED, Rypdal V, et al. Changing patterns in treatment, remission status, and categories in a long-term Nordic cohort study of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2022 May;74(5):719–727.
2. Nordal E, Zak M, Aalto K, et al. Ongoing disease activity and changing categories in a long-term Nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011 Sep;63(9):2809–2818.
3. Onel KB, Horton DB, Lovell DJ, et al. 2021 American College of Rheumatology guideline for the treatment of juvenile idiopathic arthritis: Therapeutic approaches for oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2022 Apr;74(4):521–537.
4. Fink CW. Proposal for the development of classification criteria for idiopathic arthritides of childhood. J Rheumatol. 1995 Aug;22(8):1566–1569.
5. Rumsey DG, Laxer RM. The challenges and opportunities of classifying childhood arthritis. Curr Rheumatol Rep. 2020 Jan 11;22(1):4.