Remarkable Progress Seen in Pediatric Arthritis

Far more patients have inactive disease and damage has declined

MedPage Today, Nancy Walsh, July 10, 2019

Remarkable improvements in disease activity and damage have been seen in children with juvenile idiopathic arthritis (JIA) in the biologics era compared with the methotrexate era, Italian researchers confirmed.  Among patients with the oligoarthritis subtype of JIA treated after biologics became available, the proportion of patients with physician global assessment scores of zero, indicating no disease activity, was almost double that seen when methotrexate was the preferred treatment (63.4% vs 34.0%, P<0.0001), according to Gabriella Giancane, MD, of Università degli Studi di Genova in Genoa, Italy, and colleagues.  And the percentages of patients with ocular damage fell from 12.7% to 0.7% from the methotrexate era to the biologics era, the researchers reported in Arthritis Research & Therapy.

Two major breakthroughs in the treatment of JIA have occurred in recent decades: the introduction of methotrexate in the mid-1980s and the approval of biologic agents in the 2000s.
The shift in recent years to early, aggressive intervention to prevent long-term disease damage has resulted in many JIA patients being able to achieve clinically inactive disease, and recently published recommendations on treating to target are likely to result in additional improvements in outcomes.  However, the benefits in outcomes seen during the biologic era -- with the attendant safety concerns associated with immune suppression and the substantial expense -- have not been fully quantified, so Giancane and colleagues reviewed the data from two cross-sectional studies, one of patients with disease onset from 1986 to 2002 (the methotrexate era) and the second with onset from 2002 to 2011 (the biologics era). The two groups included 239 and 269 patients, respectively.  The cross-sectional assessments for the methotrexate group took place from 2002 to 2006, while the outcome assessments for the biologics group took place from 2015 to 2017. All participants had at least 5 years of disease duration at the time of the cross-sectional assessment, and unlike other recent surveys, the same outcome criteria were utilized for the two cohorts, allowing valid comparisons.

Patients were classified as having oligoarthritis or polyarthritis, depending on whether 5 or more joints were involved.  About 80% of patients in both the methotrexate and biologics era groups were female, and median age at disease onset was about 3 in the earlier group and 2.5 in the later cohort. Few patients in either group were taking systemic glucocorticoids at the cross-sectional visit.  Patients in the biologics era had greater improvements in disease activity in multiple efficacy outcomes. Among those with oligoarthritis, the proportion of patients with inactive disease on the Juvenile Disease Activity Score 10 (JADAS10) was 28.2% in the methotrexate era and 52.6% in the biologics era (P=0.0015). Patients with low disease activity on the JADAS10 were 34.1% and 55.1%, respectively (P=0.0070).

For patients with polyarthritis, 18.9% had physician global assessments of zero in the methotrexate era compared with 57.1% in the biologics era (P<0.0001). On the JADAS10, inactive disease was seen in 16.5% versus 40.5% (P=0.0002) and low disease activity was achieved by 28.7% versus 61.9% (P<0.0001).  Damage was assessed on the Juvenile Arthritis Damage Index, divided into articular (JADI-A) and extra-articular (JADI-E) categories. Articular components included temporomandibular, shoulder, elbow, wrist, hip, knee, and ankle, while extra-articular components included ocular damage, osteoporosis, scoliosis, leg length inequality, and growth failure.

The proportion of patients who had more than one JADI-A item with damage was higher in the methotrexate era (17.6% vs 11% for oligoarthritis and 52.6% vs 21.8% for polyarthritis.) For JADI-E items, the proportions again were higher in the methotrexate group, at 26.5% versus 16.2% for oligoarthritis and 31.4% versus 13.5% for polyarthritis.  The only damage items observed in more than 5% of patients in the biologics era were temporomandibular among both oligoarthritis and polyarthritis patients, leg length inequality in oligoarthritis, and ankle damage in polyarthritis. The persistence of leg length inequality is a recognized complication of knee arthritis and highlights the need for intra-articular steroid injections, while the prevention of ankle damage remains difficult because of the structural complexity of that joint, the researchers explained. On a multivariate analysis, articular damage was associated with these factors:

  • Methotrexate era versus biologics era (OR 2.68, 95% CI 1.72-4.15)
  • Polyarthritis versus oligoarthritis (OR 3.75, 95% CI 2.36-5.96
  • )Older age at disease onset (OR 1.07, 95% CI 1.0-1.14)
  • Longer disease duration (OR 1.11, 95% CI 1.04-1.19)
  • For extra-articular damage, there was once again an association for the methotrexate era versus the biologics era (OR 2.52, 95% CI 1.62-3.92).

"These findings provide a demonstration that the recent therapeutic progresses have improved markedly the outlook of children with JIA as compared with the pre-biologic era," the researchers observed.  However, further improvements in treatment are still needed, with some children continuing to experience refractory disease and consequent damage.  A limitation of the study was the lack of imaging outcomes.

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