JIA

Biologic switching in JIA: does changing class affect outcomes?


Biologic switching is common in children and young people with juvenile idiopathic arthritis (JIA) a UK study shows, with no evidence of a benefit of switching classes of biologic for subsequent treatment.

More than one-fifth of young patients with polyarticular-course JIA started a second biologic when a first tumour necrosis factor inhibitor (TNFi) was ineffective – but the response to a second biologic was similar between patients who switched to a second TNFi and those who switched to another class of biologic, investigators reported in The Lancet Rheumatology.

Professor Kimme Hyrich, a rheumatologist from the University of Manchester who led the analysis, told the limbic the findings should reassure clinicians that working within the current NHS England biologic prescribing guidelines appears to still be an appropriate thing to do.

Recommending that the majority of patients with JIA switch to a second TNFi, the UK treatment pathway is contrary to that in the 2019 guidelines of the American College of Rheumatology (ACR), which recommends patients switch to a non-TNFi, such as tocilizumab or abatacept.

Professor Hyrich attributed the differences in guidelines to a lack of high quality evidence and consensus among experts. She noted this was the first observational study to report on the extent of multibiologic switching in children and young people with JIA in the UK, and the first to compare the effectiveness of different biologics after the failure of a first biologic in this cohort.

The analysis of two parallel UK biologic cohort studies of children and young people with JIA included 1,152 patients starting their first biologic from 2010 onwards, most of whom (92%) started treatment with a TNFi. Of the cohort, 23% of patients went on to receive a second biologic and 5% received at least three during a median follow-up time of 2.2 years from initiation of their first biologic.

Switching often occurred within the same class of biologic rather than between different classes of biologic, with most patients switching to a second TNFi and many cycling onto their third TNFi despite the availability of alternative biologic therapies.

Among 240 patients with polyarticular-course JIA, 81% started a second TNFi and 19% started a non-TNFi after an initial TNFi had failed.

Surprising results

Professor Hyrich said it was “surprising” that the choice of second treatment did not affect the proportion of patients who achieved an ACR Pedi 90 response or minimal disease activity.

“I thought we might have seen different outcomes when children were switched to a different class of therapy,” she said.

She pointed out, however, that the number of patients for whom outcome data was available was small. JIA is a relatively rare disease, with only 20% of patients estimated to start biologic therapy within the first three years after diagnosis and one-fifth of these patients switching to a second biologic.

“Therefore, this analysis might not be powered to detect smaller differences in outcome, or differences between individual biologic therapies.”

Ideally, a randomised trial comparing different second biologics could help address this question with more certainty, but Professor Hyrich noted that with a rare disease such as JIA it was difficult to get the large numbers of patients needed to achieve sufficient power in head-to-head trials.

“I think we need to expand the treatment numbers through collaborations with colleagues in the US, which is something we’re exploring, and it will be interesting to see whether in an American setting where they have different guidelines whether they get the same results,” she said.

In the meantime, Professor Hyrich said this study highlighted that although most patients with JIA tolerate biologic treatment well and have sustained disease control, some do not respond to, or cannot tolerate treatment.

“The situation where we do need to choose a second anti-TNF or biologic therapy has been confirmed by these findings,” she said.

Also, while the patterns of switching generally reflected guideline recommendations, they also showed there was some division of opinion among paediatric rheumatologists.

“We have seen different practices in different children across different centres,” said Professeo Hyrich.

“We do have more choice now than we did 10 years ago, and it might be that more doctors might be willing to try alternative therapies. In certain situations I think we might see more switching between therapies rather than within class.”

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