Early intervention with biological therapies to treat young patients with juvenile idiopathic arthritis (JIA) is more effective in reducing disease activity and improving quality of life than using only standard therapies first, a study found.
The study, “Timing matters: real-world effectiveness of early combination of biologic and conventional synthetic disease-modifying antirheumatic drugs for treating newly diagnosed polyarticular course juvenile idiopathic arthritis,” was published in the journal RMD Open.
Two therapeutic strategies can be followed upon a JIA diagnosis. In the first, more standard approach, patients can be started on a conventional treatment regime, in which synthetic disease-modifying antirheumatic drugs (DMARDs) — such as the immunosuppressant methotrexate — are prescribed. If patients fail to respond adequately, they are then treated with biological DMARDs.
The second, more aggressive strategy is to use both synthetic and biological medicines early on. Dose reductions or treatment discontinuation can follow, depending on the ensuing clinical benefits. Clinical trial results have suggested that an early, aggressive combination strategy including methotrexate works better than the immunosuppressant alone.
However, real-world evidence comparing these two approaches is lacking.
To learn more, investigators at the Cincinnati Children’s Hospital Medical Center analyzed the medical records of 465 children and adolescents, ages 1-19, who had been newly diagnosed with one of the subtypes of JIA.
The team identified 330 patients initially treated with the conservative strategy, including a standard therapy — mostly methotrexate — for at least three months after diagnosis.
A total of 135 children were treated within two months of diagnosis with a combination of primarily methotrexate and either the biological therapy Enbrel (etanercept), by Amgen or Humira (adalimumab), by AbbVie.
The aim was to compare the outcomes of these two groups — as measured by the clinical Juvenile Arthritis Disease Activity Score (cJADAS) — at the study’s start (baseline), and at six- and 12-month follow-up visits. Measurements on the cJADAS tool range from 0 to 30, with a higher score indicating greater disease activity.
Health-related quality of life (HRQoL) at 12 months also was examined with the Pediatric Quality of Life Inventory (PedsQL) questionnaire, in which a higher score — measured from 0 to 100 — describes better quality of life.
The results revealed that, while those in the early aggressive treatment group had significantly more active disease at baseline compared with the patients receiving standard treatment (16.08 vs 12.39), this difference disappeared after six months (6.47 vs 6.91) and 12 months (5.45 vs 5.25).
A statistical calculation to remove treatment selection bias — since patients had not been randomly assigned to either group — predicted that if all had received early combination therapies, cJADAS would be 2.17 points lower on average at six months compared with standard treatment. Adding biological DMARDs after six months of standard therapy was no different than continuing on standard treatment alone, the results showed.
Likewise, the quality of life score was significantly worse at the study’s start in the early aggressive treatment group. However, no differences were found at six and 12 months between the two groups.
An additional analysis predicted that the early treatment approach would lead to a clinically meaningful 6.35-point improvement in PedsQL over the conservative treatment after 12 months.
“A window of opportunity may exist where early effective DMARD treatment could address underlying disease pathophysiology [processes], prevent structural damage in joints and prevent functional impairment,” the scientists said.
“This study offers real-world evidence supporting the effectiveness of early aggressive treatment, consistently with the results from existing RCTs [randomized controlled trials],” they added.