JIA Patients Should Stay on Biologics 2 Years After Remission

Those with inactive disease relapsed 6 months after stopping treatment

Diana Swift,October 12, 2017 from MedPage Today

Action Points

Children with oligoarticular and polyarticular juvenile idiopathic arthritis (JIA) who stopped treatment less than 2 years after remission had a greater chance of relapsing after discontinuing biologics, according to Italian investigators.

Among 135 eligible children from a patient cohort enrolled at three Italian centers more than three-quarters flared after discontinuing biologics at a median follow-up of 6 months post-therapy, reported Rolando Cimaz, MD, of Anna Meyer Children's Hospital of Florence, and colleagues.

Those with systemic disease were less likely to flare than those with other categories of JIA, they wrote in Arthritis Care & Research.

The viability of maintaining drug-free remission in JIA and other arthritis has become a major focus of current rheumatologic research.

"These data seem to suggest that biologic treatment, in selected JIA categories, might be continued for at least 2 years after achieving clinical remission," the authors noted.

The patients had an overall median age of 14.6 years and 38.6% were female. During 2000-2016, the 135 patients were being treated with multiple biologics: etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), anakinra (Kineret), rituximab (Rituxan), and abatacept (Orencia), with concurrent methotrexate given in 92% of cases.

To be eligible for the study, patients had to have achieved inactive disease for at least 6 months after their first cycle of biologic therapy (alone or in combination), and to have had no medication for at least 3 months.

According to the authors, 37.8% had discontinued biologic therapy for persistent inactive disease, with discontinuation occurring at a median of 20 months from onset of biologic therapy, which had started at a mean age of 8.98± years.

At median follow-up of 6 months in drug-free remission, 75.6% (102/135) had suffered a relapse after stopping treatment. This finding "is hardly surprising, since it has already known that neither MTX nor biologic therapies for JIA normalize immune function," the authors stated.

The probability of maintaining remission after treatment cessation was higher present in systemic-onset disease (Mantel-Cox chi-square test 8.31, P<0.004).

In a 2016 assessment of risk factors, other researchers reported that children with systemic JIA had the lowest probability of flare after achieving remission, while those with RF-positive polyarticular disease had the highest.

In patients with polyarticular and oligoarticular disease, those who received biologics for more than 2 years after achieving remission had a higher probability of maintaining such remission off therapy at 18.64 months versus 11.51 months (P<0.009; Mantel-Cox chi-square test 2 9.06, P<0.002). No other clinical variable was significantly associated with a long-lasting remission, nor was antinuclear antibody-positivity associated with a greater probability of flare (Mantel-Cox chi-square test 0.08, P=0.77).

"The findings certainly comport with what I've seen in practice and the literature. It's good to have your impressions from clinical experience confirmed that the longer you keep children in control on medication, the better they do long term," said Harry L. Gewanter, MD, of Pediatric & Adolescent Health Partners in Richmond, Virginia.

"The longer you keep a child in remission, the better the odds they will stay in remission," Gewanter told MedPage Today. But he cautioned that "the question every parent asks is 'How long is my child going to be on medication?'" He said he has kept JIA patients on medication until they have zero active disease for at least a year.

"Kids with JIA have a lot of up and downs -- the natural history of the disease is one of ups and downs," said Gewanter, who was not involved in the study. "With the newer biologics you're able to get people into remission more frequently, but they may not stay there and that's the conundrum for all of us."

Among relapsing participants in the Italian study, 34.1% were restarted on their original biologic, 19.3% were switched to a different biologic, 4.4% were restarted on methotrexate, 11.9% were given intraarticular corticosteroid injection, 2.2% were given no treatment, and 0.7% were treated with another antirheumatic.

A year after therapy discontinuation, only 31.1% (42/135) of study patients were still in remission, suggesting that the probability of flare is higher than in some previous research and more similar to the 63% relapse rate. For those maintaining remission, disease stayed inactive for a median of 53 months.

Study limitations included its retrospective chart-based design, the variability across centers in decision-making about the biologic therapy initiation and cessation, and the unavailability of juvenile arthritis disease activity scores for some patients. Also, there was a small number of patients in certain JIA subtypes, which precluded identifying potential clinical descriptors of relapse after biologic cessation, and confined analysis to more homogeneous groups with an equal distribution of ANA positivity.

Finally, the authors excluded patients who had more than one biologic treatment cycle before achieving remission, which potentially left out children with more refractory disease.

Gewanter said he would like to see trials with longer-term follow-up. "Studies where you're tracking how long patients stayed on medicines and whether it makes a difference down the road if these are stopped at 1 year without disease or 2 years without disease," he said.

Cimaz and co-authors disclosed no relevant relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner