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The currently favored approach to treatment for systemic juvenile idiopathic arthritis (JIA) involves the early institution of biologic therapy, and short-term outcomes have been generally excellent, reported Timothy Beukelman, MD, of the University of Alabama at Birmingham.

In a prospective observational study that included 73 patients with systemic JIA, clinically inactive disease was observed at 9 months in 57% of patients who had been initially treated with an interleukin (IL)-1 or IL-6 inhibitor, he said at a press conference at the .

Systemic JIA is a rare form of JIA, which differs from the other subtypes in that it is characterized by systemic inflammation manifesting as high spiking fevers and markedly elevated inflammatory markers.

Randomized clinical trials have demonstrated efficacy for IL-1 and IL-6 inhibitors in systemic JIA, but those trials did not enroll patients at the time of diagnosis. Additional uncontrolled published data have suggested that early treatment with biologics likely produces superior short-term outcomes, so the optimal treatment has been unclear.

A group of experts from the conducted surveys and consensus meetings to determine the most commonly used treatments and identified four main consensus treatment approaches:

• IL-1 inhibition with anakinra (Kineret)

• IL-6 inhibition with tocilizumab (Actemra)

• Methotrexate, with systemic glucocorticoids as needed

• Methotrexate, with systemic glucocorticoids alone

were published in 2012. However, the treatment of this condition has changed dramatically over the last 10 to 15 years with the widespread use of the IL-1 and IL-6 blockers.

"Prior to the availability of biologic agents the treatment of systemic JIA often required the use of systemic glucocorticoids, often in large doses and for extended periods of time. However, the adverse events associated with systemic glucocorticoids can be substantial, so it's usually desirable to limit their use as much as possible," Beukelman said.

Therefore, to see what the typical treatment patterns are today beginning at the time of diagnosis rather than later in the course of disease, he and his colleagues conducted a study known as FROST (First Line Options for SJIA Treatment).

The data were analyzed with the two biologics combined versus the methotrexate/glucocorticoid groups combined.

Patients' median age was 6.8 years, 60% were male, and 63% were white. Mean days since symptom onset was 46, and median days since diagnosis at the start of treatment was only 2.

The mean number of active joints was 6.6, median erythrocyte sedimentation rate was 73 mm/h, median C reactive protein was 15.4, and median ferritin level was 829 ng/mL. Median score on the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) was 17.

The initial treatment assignments were made by the treating physician with discussions with the family. Switching of treatment could be done at any time in the study, and outcomes were analyzed according to the initial treatment assignment.

Of the 73 patients enrolled, 86% received initial treatment with a biologic; only 10 patients started on nonbiologic therapy, so no statistical comparison could be made. Moreover, during follow-up, five of the 10 patients in the nonbiologic group switched to a biologic at time points ranging from 10 to 101 days after study enrollment.

A total of 53 patients had outcome data available at 9 months. The primary endpoint of clinically inactive disease without current glucocorticoid use was met by 27 of 47 patients on biologic therapy (57%) and by three of six patients in the non-biologic group (50%), Beukelman said.

The secondary endpoint of cJADAS10 ≤1 plus no fever without current glucocorticoid use was met by 29 of 43 patients in the biologic group (67%) and by three of five in the nonbiologic group (60%). A cJADAS10 ≤2.5 was met by 75% of patients overall.

"The short-term outcomes in FROST were generally excellent," Beukelman said, noting that the patients who participated in the study remain enrolled in the CARRA registry, so data collection is ongoing to provide further long-term outcome information.

During the press conference, he was asked whether there is any actual role for methotrexate monotherapy today, given the results of the study. "That was the question we tried to answer, but because the vast majority were started on a biologic we didn't have enough data from the nonbiologic arm to make that assessment," he answered.

It does appear that many pediatric rheumatologists now use biologics because of their own experiences and the published literature, he noted.

"I think the important outstanding questions are what do the long-term outcomes look like, and can we confirm the safety of the IL-1 and IL-6 inhibitors. In the short-term they are highly effective for most patients and they seem relatively safe," Beukelman noted.

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