Study Recommends Biologic Dose Escalation in Patients with Juvenile Idiopathic Arthritis

Recent investigation into the use of high-dose biologics showed that dose escalation in patients with juvenile idiopathic arthritis (JIA) was effective in improving disease control, provided that specific biologic agents are used.

The study, led by Colleen K. Correll, MD, contributed to the increasingly popular trend of biologic use for the treatment of young patients, and was one of the first published studies to discuss the efficacy and safety of the process.

Correll and her colleagues found that within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, 20% of children with JIA received high-dose biologics, though the use of biologics varied by state.

The team considered biologics to be integral in the treatment of juvenile idiopathic arthritis, writing that pediatric rheumatologists may increase the dosage of biologics beyond standard range in order to achieve better disease control.

They conducted a retrospective study of patients with JIA enrolled in the CARRA Registry from June 30, 2015 to December 6, 2019.

The registry defined high-dose as 40% higher than the standard dose issued, and each dose was approved by the US Food and Drug Administration (FDA) whenever access was available.

The retrospective study contained 5352 patients, 20.1% (n = 1080) of whom ever received high-dose treatment prior to the study.

The levels of dosage within the group were standard, high, and low. Most participants (69%) continued standard dosing after enrollment in the Registry. Those who did change the dosage or switched to a new biologic tended to have higher disease activity scores.

The most used biologic in the high-dose group was adalimumab (68.3%), whereas among the switch biologic group, most participants were receiving etanercept (71.0%).

Investigators noted that weekly adalimumab had been demonstrated to be safe and effective in the treatment of other pediatric autoimmune diseases and adult rheumatoid arthritis (RA), which they believed explained why it was the most used biologic to be used (during high-dose studies.

However, high-dose etanercept has not been demonstrated to be effective in treating JIA, which resulted in participants switching to different biologic therapies.

Discontinuation rates and serious adverse events (SAE) were noted in all participant groups. While they did occur at a higher rate in high-dose and switched dose groups, the team considered them to be uncommon.

The 6-month outcomes observed by Correll and colleagues showed that participants with an increased dose, as well as those who switched to other biologic therapies, showed greater improvement.

“The 6-month outcomes were similar between the high-dose and biologic switch groups, and both groups had improvements in disease activity measures,” the team wrote. “These findings support the idea that if a patient with JIA has inadequately controlled disease, increasing to high-dose biologic is a reasonable option, as is switching biologics.”

High-dose participants were also compared to the standard, no-change group.

While a higher trend of SAEs was found in the high-dose group, investigators attributed it to the likelihood of more severe cases within the group. Allowing for that likelihood, they found the high-dose group to be a reasonable and preferred option for patients with inadequately controlled disease on standard doses.

Although the team lacked dose-comparison studies for the vast majority of drugs used in the study, they considered it to be successful.

As noted in the study, the dosing of biologic agents in children with pediatric rheumatic diseases had not been studied comprehensively in the past. However, the study showed a positive response to increased doses in patients with JIA.

Correll and her colleagues called for further studies to be made regarding biologic use in children, as well as comparative studies in adult patients. Despite this, the team considered high-dose biologic treatment to be safe and effective.

“Since children generally have fewer co-morbidities than adults and given our concern of active arthritis impacting the child’s growing skeleton, pediatric rheumatologists may have a greater willingness to use higher doses of biologics compared to adult rheumatologists,” the team wrote. “However, it would be important to compare studies similar to ours in adult patients if high doses are used in the real-world setting.”

The study, “Effectiveness and Safety of High-Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance,” was published online in Arthritis Care and Research.