No Evidence to Support Biologic Switching Guidelines for Juvenile Idiopathic Arthritis

By Marilynn Larkin

April 02, 2020

NEW YORK (Reuters Health) - For young people with juvenile idiopathic arthritis who don't achieve disease control, switching to a different class of biologic is unlikely to be beneficial, researchers say.

The observational study yielded no evidence to support or refute the 2015 National Health Service England guidelines, which recommend switching most patients to a second TNF inhibitor, or the 2019 guidelines of the American College of Rheumatology, which recommend switching patients to an alternative class of biologic (e.g., tocilizumab or abatacept).

"There are differing opinions on which biologic drugs (these children) should receive, and in which order, should they not respond to or be intolerant of methotrexate and a first biologic, often an anti-TNF," Dr. Kimme Hyrich of the University of Manchester, UK, told Reuters Health by email. "Our study found that after a first biologic, usually a TNF inhibitor, similar outcomes were seen after one year between children who started a second anti-TNF or an alternative class, primarily the IL-6 inhibitor tocilizumab."

Due to the study's small size, she noted, "it was not possible to study further whether there are certain children who may still benefit more than others from switching class."

"This emphasizes the need to continue to recruit children into clinical studies so that a large evidence base can be generated to better inform practice for this relatively uncommon disease," she added.

As reported in The Lancet Rheumatology, Dr. Hyrich and colleagues analyzed 2,361 young people enrolled upon initiation of biologic therapy in two parallel UK cohort studies between 2004 and 2019.

From 2010 onwards, 1,152 patients started their first biologic, mostly (91%) with TNF inhibitors. The median follow-up was 2.2 years, during which time, 270 (23%) started a second biologic; 61 (5%) started a third biologic; and 11 (1%) started a fourth.

In a subgroup of 240 patients with polyarticular course juvenile idiopathic arthritis, 194 (81%) started a second TNF inhibitor and 46 (19%) started a different class of biologic after an initial TNF inhibitor failed.

The choice of second therapy - i.e., second TNF inhibitor or another class of biologic - did not affect the proportion of patients who achieved an American College of Rheumatology Pediatric (ACR Pedi) 90 response (adjusted odds ratio, 2.5) or minimal disease activity (aOR, 1.6).

The authors note that the study did not capture data on treatment adherence, drug levels, or anti-drug antibody concentrations, which might have influenced treatment response - nor was the route or frequency of biologic administration investigated, which might have influenced treatment choice.

Further, the time to initiation of a second biologic was more than 2.5 years after the initiation of a first TNF inhibitor in 25% of children. Outcomes might differ among children starting their second biologic in 2019, they note, including quicker cycling through biologics and, thereby, a reduction in time to treatment.

Dr. Lisette WA van Suijlekom-Smit of Erasmus Medical Center in Rotterdam, author of a related editorial, commented in an email to Reuters Health, "Information from the two combined UK registries reflects the treatment policy in daily practice in different time periods, and selected juvenile idiopathy arthritis categories. Today differs in many aspects from the early years."

Although no differences were seen between a second TNF inhibitor and tocilizumab, she said, "the numbers are probably too small to detect (differences) when comparing two effective treatments."

"The choice between all these new biologicals is more or less trial and error," she said. "A great jump forward would be identifying the best target in the inflammatory cascade, as demonstrated for systemic juvenile idiopathic arthritis. The goal must be to make the best choice based on the different (disease) categories, or even better, on disease markers or characteristics of individual patients."

"It is disappointing to realize that this evaluation of more recent data mirroring daily practice also clarifies that there is still too much treatment delay and many patients with missing disease activity variables - the objective tools to monitor disease activity in routine practice," she noted.

"The management of juvenile idiopathic arthritis has undeniably changed, but further advances have to be made," she said. "This will not be realized by introducing new biologics only; innovating the therapeutic approach with tight control and treating to target might be even more important."

SOURCE: and The Lancet Rheumatology, online March 9, 2020.